bluuebunny/crossref_metadata_2025 huggingface dataset:
Chlamydia trachomatispolymorphic membrane protein D is a species-common pan-neutralizing antigen
Authors: Crane Deborah D. , Carlson John H. , Fischer Elizabeth R. , Bavoil Patrik , Hsia Ru-ching , Tan Chun , Kuo Cho-chou , Caldwell Harlan D.
Published: January 2006

Infections caused by the obligate intracellular pathogenChlamydia trachomatishave a marked impact on human health.C. trachomatisserovariants are the leading cause of bacterial sexually transmitted disease and infectious preventable blindness. Despite decades of effort, there is no practical vaccine againstC. trachomatisdiseases. Here we report that allC. trachomatisreference serotypes responsible for sexually transmitted disease and blinding trachoma synthesize a highly conserved surface-exposed antigen termed polymorphic membrane protein D (PmpD). We show that Ab specific to PmpD are neutralizingin vitro. We also present evidence that Ab against serovariable-neutralizing targets, such as the major outer membrane protein, block PmpD neutralization. This finding suggests that a decoy-like immune evasion strategy may be activein vivowhereby immunodominant type-specific surface antigens block the neutralizing ability of species-common PmpD Ab. Collectively, these results show that PmpD is a previously uncharacterizedC. trachomatisspecies-common pan-neutralizing target. Moreover, a vaccine protocol using recombinant PmpD to elicit neutralizing Ab in the absence of immunodominant type-specific Ab might be highly efficacious and surpass the level of protection achieved through natural immunity.
Crystal structure, catalytic mechanism, and mitogenic properties of
Trypanosoma cruzi
proline racemase
Authors: Buschiazzo Alejandro , Goytia Maira , Schaeffer Francis , Degrave Wim , Shepard William , Grégoire Christophe , Chamond Nathalie , Cosson Alain , Berneman Armand , Coatnoan Nicolas , Alzari Pedro M. , Minoprio Paola
Published: January 2006

Amino acid racemases catalyze the stereoinversion of the chiral C
α
to produce the
d
-enantiomers that participate in biological processes, such as cell wall construction in prokaryotes. Within this large protein family, bacterial proline racemases have been extensively studied as a model of enzymes acting with a pyridoxal-phosphate-independent mechanism. Here we report the crystal structure of the proline racemase from the human parasite
Trypanosoma cruzi
(
Tc
PRACA), a secreted enzyme that triggers host B cell polyclonal activation, which prevents specific humoral immune responses and is crucial for parasite evasion and fate. The enzyme is a homodimer, with each monomer folded in two symmetric α/β subunits separated by a deep crevice. The structure of
Tc
PRACA in complex with a transition-state analog, pyrrole-2-carboxylic acid, reveals the presence of one reaction center per monomer, with two Cys residues optimally located to perform acid/base catalysis through a carbanion stabilization mechanism. Mutation of the catalytic Cys residues abolishes the enzymatic activity but preserves the mitogenic properties of the protein. In contrast, inhibitor binding promotes the closure of the interdomain crevice and completely abrogates B cell proliferation, suggesting that the mitogenic properties of
Tc
PRACA depend on the exposure of transient epitopes in the ligand-free enzyme.
Aβ and tau form soluble complexes that may promote self aggregation of both into the insoluble forms observed in Alzheimer’s disease
Authors: Guo Jian-Ping , Arai Tetsuaki , Miklossy Judit , McGeer Patrick L.
Published: January 2006

To date, there is no reasonable explanation as to why plaques and tangles simultaneously accumulate in Alzheimer’s disease (AD). We demonstrate here by Western blotting and ELISA that a stable complex can form between tau and amyloid-β protein (Aβ). This complex enhances tau phosphorylation by GSK3β, but the phosphorylation then promotes dissociation of the complex. We have localized the sites of this interaction by using peptide membrane arrays. Aβ binds to multiple tau peptides, especially those in exons 7 and 9. This binding is sharply reduced or abolished by phosphorylation of specific serine and threonine residues. Conversely, tau binds to multiple Aβ peptides in the mid to C-terminal regions of Aβ. This binding is also significantly decreased by GSK3β phosphorylation of tau. We used surface plasmon resonance to determine the binding affinity of Aβ for tau and found it to be in the low nanomolar range and almost 1,000-fold higher than tau for itself. In soluble extracts from AD and control brain tissue, we detected Aβ bound to tau in ELISAs. We also found by double immunostaining of AD brain tissue that phosphorylated tau and Aβ form separate insoluble complexes within the same neurons and their processes. We hypothesize that in AD, an initial step in the pathogenesis may be the intracellular binding of soluble Aβ to soluble nonphosphorylated tau, thus promoting tau phosphorylation and Aβ nucleation. Blocking the sites where Aβ initially binds to tau might arrest the simultaneous formation of plaques and tangles in AD.
RNAs induced by Epstein–Barr virus nuclear antigen 2 in lymphoblastoid cell lines
Authors: Zhao Bo , Maruo Seiji , Cooper Andrew , R. Chase Michael , Johannsen Eric , Kieff Elliott , Cahir-McFarland Ellen
Published: January 2006

Epstein–Barr virus (EBV) nuclear antigen 2 (EBNA2) association with RBP-Jκ is essential for regulation of virus and cell gene transcription and B lymphocyte transformation into infinitely proliferating lymphoblastoid cells (LCLs). To identify EBNA2-regulated cell genes in LCLs, an EBV recombinant that expresses EBNA2 with its C terminus fused in frame to a 4-hydroxytamoxifen (4HT)-dependent mutant estrogen receptor (E2HTF) was used to transform primary B lymphocytes to LCLs. In the presence of 4HT, E2HTF expression level and effects on the LMP1 promoter in transfected BJAB lymphoblasts were similar to EBNA2. In 4HT-supplemented medium, E2HTF EBV recombinant infected LCLs were also similar to EBNA2 LCLs in outgrowth but required higher serum and a restricted range of cell concentrations for consistent growth. In medium without 4HT, E2HTF localized to the cytoplasm, c-myc levels substantially decreased within 6 h, cells stopped growing, and levels of other EBNAs and LMP1 remained stable for 24 h. Over this 24-h period, 30 cell RNAs decreased 2-fold, and 51 other RNAs decreased 1.5-fold. These RNAs encode proteins important in cell adhesion or signaling, transcription, RNA processing, cell-cycle regulation, and survival. Real-time RT-PCR confirmed EBNA2-dependent expression of eight RNAs.
Integrins regulate VE-cadherin and catenins: Dependence of this regulation on Src, but not on Ras
Authors: Wang Yingxiao , Jin Gang , Miao Hui , Li Julie Y.-S. , Usami Shunichi , Chien Shu
Published: January 2006

Adhesions of cells to extracellular matrix and adjacent cells are mediated by integrins and VE-cadherin, respectively. Although these adhesion processes play crucial roles in vascular cell migration and angiogenesis, it remains unclear as to how they are coordinated to regulate cellular functions. We report here that integrin engagement by treating bovine endothelial aortic cell monolayers with beads coated with fibronectin (Fn) led to disruption of the VE-cadherin-containing adherens junctions. This disruption was accompanied by increases of tyrosine phosphorylation of β-catenin, γ-catenin, and p120
ctn
, as well as the dissociation of α-catenin and γ-catenin from VE-cadherin. We applied a membrane-targeted Src reporter based on the fluorescence resonance energy transfer technique to visualize the dynamic Src activation at subcellular levels in live cells. The integrin engagement induced by Fn-coated beads caused the activation of Src around the beads and at adherens junctions, which are subsequently disrupted. The inhibition of Src with PP1 blocked the effects of integrin engagement on adherens junctions. Although Ras can also modulate adherens junctions, the resulting patterns of phosphorylation and association of junction proteins were distinct from those induced by integrin engagement. The inhibition of Ras by RasN17 did not rescue the disruption of adherens junctions induced by integrin engagement or by Src activation. Integrin engagement by Fn-coated beads also induced a significant alteration of cortical actin filaments at adherens junctions. The results indicate that integrin engagement disrupts VE-cadherin-containing adherens junctions via the activation of Src, but not Ras, possibly as a result of modulation of the actin network.
Building with Ruins and Dreams: Some Thoughts on Realising Integrated Urban Development in South Africa through Crisis
Authors: Pieterse Edgar
Published: January 2006

It is often lamented that South African cities are beset by interminable crises: segregation, inequality, fragmentation, violence, the Aids epidemic and so on. This lament is premised on the assumption that somehow urban challenges must be stabilised, brought under control through analytical or policy tools and then the ideals of urban integration and holism can come to pass. This paper challenges this conception of urban development policy and politics by recasting crisis as an opportunity (temporarily) to align and co-ordinate energies in order to undo the deeply engraved legacies of urban segregation and fragmentation. Concretely, the argument unfolds along three guideposts. In the first section, it is proposed that there are essentially three key conditions for addressing the structural crises of urban fragmentation: vibrant city politics in a radical democratic mode; a substantial 'epistemic community' in cities that generate imaginative ideas about alternative futures premised on a set of meta-objectives and concrete intervention strategies for the city; and, sufficient investment capital (private and public) to give economic support and expression to the implementation of concrete programmes and projects in line with the ideas generated by the epistemic community for alternatives. The second section of the paper elaborates prospective meta-objectives that epistemic communities can work with in order to advance more integrative urban development based on the framework of Ayyun Malik. The third section proposes some tangible interventions to construct socially and politically projects to build alternative futures in the context of Cape Town.
On the Edge of Reason: Planning and Urban Futures in Africa
Authors: Harrison Philip
Published: January 2006

The shift in planning theory from technical-instrumental to relational conceptions of rationality is helpful in relating to urban environments in Africa that are characterised by the intersection of multiple rationalities and also by spatially extensive and shifting networks of economic and social transaction. However, the relevance of contemporary planning theory is limited by its origins within the intellectual traditions and experiences of the West. If we are to engage effectively with the multiple rationalities that are shaping the cities of the world-cities that are increasingly centred in the global South-then we must bring Western intellectual tradition into a critical relationship with the epistemologies, rationalities and value-based traditions of the non-Occidental world. This paper argues that post-colonial literature and theory may provide some of the intellectual resources needed to sustain such an engagement, as post-colonial thought directs attention to the hybrid intellectual formations and practices that emerge in the on-going interaction between colonised and coloniser. By using Johannesburg as the prism through which to look at cities and at planning, this paper provides some thoughts on how to construct an 'other way' of thinking that is situated both within and outside dominant representations.
Low-high and high-low biphasic injection forms in computed tomography examinations of the upper abdomen
Authors: Martí-Bonmatí L. , Arana E. , Tobarra E. , Sierra C.
Published: January 2006

Purpose: To analyze the influence of different biphasic and monophasic injection rate protocols in abdominal computed tomography (CT).

Material and Methods: A randomized, consecutive, parallel group study was designed and conducted in 60 patients studied with the same CT helical protocol. Patients were randomly distributed into three groups: (A) monophasic (120 ml at 2.5 ml/s); (B) low-high biphasic (120 ml, first 60 ml at a rate of 2 ml/s, the other 60 ml at 2.5 ml/s); and (C) high-low biphasic (120 ml, first 60 ml at a rate of 2.5 ml/s, the other 60 ml at 2 ml/s). All patients were injected with 300 mg I/ml non-ionic contrast media at a fixed delay time of 55 s. Contrast enhancement efficacy was evaluated by attenuation coefficient measurements.

Results: Although non-significant, monophasic protocol enhancements were higher than biphasic protocol enhancements in all measurements except aortic bifurcation ( p = 0.003). At this level, biphasic protocols obtained an increased mean enhancement from 7.6% to 2.5% compared to monophasic protocols.

Conclusion: Monophasic contrast agent injection in helical CT of the upper abdomen produces a higher enhancement of parenchymal and venous structures. No significant difference was observed between low-high and high-low biphasic protocols.
Characterization of adrenal adenomas and metastases: correlation between unenhanced computed tomography and chemical shift magnetic resonance imaging
Authors: Rescinito G. , Zandrino F. , Cittadini G. , Santacroce E. , Giasotto V. , Neumaier C. E.
Published: January 2006

Purpose: To evaluate the correlation of absolute attenuation values of unenhanced computed tomography (CT) with signal intensity (SI) quantitative analysis on chemical shift (CS) magnetic resonance (MR) imaging in differentiating adrenal adenomas from metastases.

Material and Methods: Forty-one adrenal masses (27 adenomas, 14 metastases) were studied with CS MR imaging and unenhanced CT. MR included T1-weighted breathhold gradient-echo in-phase (IP) and opposed-phase (OP) sequences. The SI index (SI-i) [(SIIP−SIOP/SIIP)]×100% and chemical-shift ratio (CS-r) relative to the spleen [(SIlesion/SIspleen)OP/(SIlesion/SIspleen)IP] were calculated for each lesion. CT absolute attenuation values were also determined.

Results: The mean attenuation value of metastases was significantly greater than that of adenomas (<0.0001). On MR, the mean SI-i of adenomas was significantly greater than that of metastases ( P<0.0001) and no overlaps were evident. The CS-r of malignant and benign lesions overlapped considerably, and five adenomas (all with indeterminate Hounsfield Unit values at CT) were misclassified as potentially malignant. CT attenuation values were significantly correlated with both MR quantitative analyses.

Conclusion: Since CS MR imaging and CT both depict the presence of lipids within adrenal lesions, absolute attenuation values are highly correlated with MR quantitative analysis. SI-i is the most reliable tool for differentiating adrenal adenomas from metastases, showing better accuracy than lesion-to-spleen CS-r, in particular for adenomas with indeterminate absolute attenuation values.
64-slice computed tomography assessment of coronary artery stents: a phantom study
Authors: Mahnken A. H. , Mühlenbruch G. , Seyfarth T. , Flohr T. , Stanzel S. , Wildberger J. E. , Günther R. W. , Kuettner A.
Published: January 2006

Purpose: To compare the use of a new 64-slice computed tomography (CT) scanner with 16-slice CT in the visualization of coronary artery stent lumen.

Material and Methods: Eight different coronary artery stents, each with a diameter of 3 mm, were placed in a static chest phantom. The phantom was positioned in the CT gantry at an angle of 0° and 45° towards the z-axis and examined with both a 64-slice and a 16-slice CT scanner. Effective slice thickness was 0.6 mm with 64-slice CT and 1 mm with 16-slice CT. A reconstruction increment of 0.3 mm was applied in both scanners. Image quality was assessed visually using a 5-point grading scale. Stent diameters were measured and compared using paired Wilcoxon tests.

Results: Artificial lumen reduction was significantly less with 64-slice than with 16-slice CT. Average visible stent lumen was 53.4% using 64-slice CT and 47.5% with 16-slice MSCT. Most severe artifacts were seen in stents with radiopaque markers. Using 64-slice CT, image noise increased by approximately 30% due to thinner slice thickness.

Conclusion: Improved spatial resolution of 64-slice CT resulted in superior assessment of coronary artery stent lumen compared to 16-slice CT. However, a relevant part of the stent lumen is still not assessable with multi-slice CT.
Split renal function in patients with suspected renal artery stenosis: a comparison between gamma camera renography and two methods of measurement with computed tomography
Authors: Björkman H. , Eklöf H. , Wadström J. , Andersson L.-G. , Nyman R. , Magnusson A.
Published: January 2006

Purpose: To validate a method for calculating split renal function from computed tomography (CT) compared with gamma camera renography, and to test a new method for the measurement based on a volume-rendering technique.

Material and Methods: Thirty-eight patients, aged 65.7±11.6 (range 37.8–82.1) years, who had undergone both CT angiography and gamma camera renography for a suspected renal artery stenosis were included in this study. Split renal function was calculated from the CT examinations by measuring area and mean attenuation in the image slices of the kidneys, and also by measuring volume and mean attenuation from a 3D reconstruction of the kidneys. Gamma camera renography with 99mTc-MAG3 with or without captopril enhancement was used as a reference.

Results: The 2D CT method had good correlation with renography ( r = 0.93). Mean difference was 4.7±3.6 (0–12) percentage points per kidney. There was also excellent correlation between the two CT methods ( r = 1.00).

Conclusion: CT is equivalent to renography in determining split renal function, and the measurement from the CT examination can be made more quickly and equally accurately with a 3D technique.
Imaging characteristics of hepatocellular carcinoma using the hepatobiliary contrast agent GD-EOB-DTPA
Authors: Jung G. , Breuer J. , Poll L. W. , Koch J. A. , Balzer T. , Chang S. , Mödder U.
Published: January 2006

Purpose: To evaluate the ability of contrast-enhanced magnetic resonance imaging (MRI) with Gd-EOB-DTPA in comparison with non-enhanced imaging and spiral computed tomography (CT) to provide additional information for classification and characterization of hepatocellular carcinoma.

Material and Methods: Forty patients with histopathology-proven hepatocellular carcinoma were selected for this subgroup analysis from a phase-III multicenter study in 235 patients with known or suspected liver lesions. The primary analysis was comparison of the proportion of hepatocellular carcinoma correctly classified and characterized by combined pre-/post-contrast MRI compared with pre-contrast MRI alone or with spiral CT. All images were evaluated on site, and in a blinded reading by three independent readers off site.

Results: In the on-site evaluation, the lesions were correctly classified as a malignant tumor with combined MRI in 90.3%, with pre-contrast imaging alone in 82.9% and with spiral CT in 87.8% (n.s.). The proportion of correct characterization (lesion type diagnosis) with combined MRI was 85.4%, 75.6% for pre-contrast imaging, and 77.5% for spiral CT (n.s.), respectively.

In the blinded reading, one reader showed a significant increase in the proportion of correctly characterized lesions by 27% ( P<0.05). The other two readers showed a reduction in the proportion of correct characterization by 12% and 15%, respectively (n.s.).

Conclusion: With regard to lesion classification, no difference was found between combined pre-/post-contrast MRI and spiral CT. A non-significant trend in favor of Gd-EOB-DTPA-enhanced MRI with regard to characterization of hepatocellular carcinoma was found, although the CT scans were not optimized as the MRI scans.
Phytate technetium-99m versus dextran 500 technetium-99m in the sentinel lymph node biopsy
Authors: Paiva G. R. , Filho R. S. O. , Ferreira L. M. , Wagner J. , Nogueira S. A. , Novo N. F. , Juliano Y. , Rocha J. L. B. S.
Published: January 2006

Purpose: To study which of the two most used radiopharmaceutical drugs for the sentinel lymph node (SLN) biopsy procedure (dextran 500 99mTc and phytate 99mTc) best defines the SLN and migrates less to other lymph nodes.

Material and Methods: Thirty-two rats, separated into two groups, underwent lymphoscintigraphy examination with either dextran or phytate followed by sentinel (popliteal), lumbar, and inguinal lymph node biopsy. Radiation was detected with a gamma probe.

Results: The statistical study indicated count rates significantly higher in the SLN than in the other basins for both the dextran ( P<0.01) and phytate groups ( P<0.001). There was no statistically significant difference concerning SLN absorption in either group ( P = 0.2981). In the dextran group, migration occurred to 1.5 lymphatic basins with counting higher than 10% of that found in the SLN versus 0.8 in the phytate group ( P = 0.0023). Migration was thus higher in the dextran group ( P = 0.0207).

Conclusion: There was no statistically significant difference between dextran and phytate in the SLN identification, but the phytate migrated to fewer lymphatic basins beyond the SLN and with less intensity.
Radiography following perinatal death: a review
Authors: Olsen Ø. E.
Published: January 2006

Radiography of the perinatally dead infant provides detailed information about the skeleton and is valuable as an adjunct to autopsy. This article reviews the potential benefits and discusses the pitfalls in assessment of growth stage. Reference charts for individual bone lengths and secondary ossification centers are presented.
Virtual bronchoscopy versus thin section computed tomography in evaluation of moderate and low grade stenoses: receiver operating characteristic curve analysis
Authors: Maniatis P. N. , Triantopoulou C. C. , Tsalafoutas I. A. , Lamprakis C. K. , Malagari K. S. , Konstantinou K. , Christodoulou E. , Papailiou J. , Kelekis D. A.
Published: January 2006

Purpose: To evaluate the impact of virtual bronchoscopy, under proper threshold settings, on observer level of confidence in the assessment of bronchial abnormalities producing stenoses ⩽75% compared to interpretation of thin section computed tomography (CT) images.

Material and Methods: Sixty-five patients with fiberoptic bronchoscopy positive for tracheobronchial abnormalities were evaluated in a blinded observer study using a commercially available virtual endoscopy software package. The findings of virtual endoscopy were compared with those of fiberoptic bronchoscopy using receiver operating characteristic curves (ROCs) and other statistical tools.

Results: A total of 102 lesions were identified by fiberoptic bronchoscopy, with 44 of these producing bronchial stenoses ⩽75%. Concerning the latter lesions, for virtual bronchoscopy the areas under the ROCs were 0.93 and 0.96 for the two observers, respectively, while for thin section CT the corresponding values were 0.86 and 0.88; the differences observed were statistically significant. Contrary to thin section CT, virtual bronchoscopy did not show statistically significant differences from fiberoptic bronchoscopy regarding estimation of degree of stenosis.

Conclusion: Virtual bronchoscopy under proper threshold settings has a statistically significant impact on observer performance where moderate and low-grade bronchial stenoses are concerned and gives an estimate of the degree of stenosis more precisely than thin section CT.
Book Review
Authors: Heilo Arne
Published: January 2006

Interventional Radiology in Cancer – Medical Biology. Edited by A. L. Baert, L. W. Brady, and H.-P. Heilmann, et al. – Diagnostic Imaging. A. Adam, R. F. Dondelinger, and P. R. Mueller. Springer-Verlag, Berlin, Heidelberg, New York 2004. ISBN 3-540-41873-3. 284 pages, 444 figures and 10 tables.
Non‐fatal heroin overdose, treatment exposure and client characteristics: Findings from the Australian Treatment Outcome Study (ATOS)
Authors: DARKE SHANE , WILLIAMSON ANNA , ROSS JOANNE , TEESSON MAREE
Published: January 2006

The relationship between treatment exposure, drug use, psychosocial variables and non‐fatal heroin overdose was examined among a cohort of 495 heroin users, re‐interviewed at 12 months. The 12‐month overdose rate declined from 24% to 12%, and the proportion administered naloxone declined from 15% to 7%. There were significant reductions in overdose among those who entered maintenance therapies (22% to 4%) and residential rehabilitation (33% vs. 19%) at baseline, but not among those who entered detoxification or were not entering treatment. The total number of treatment days received over the follow‐up period was associated independently with a reduced risk of overdose. Each extra treatment day was associated with a 1% reduction in risk of overdose over the follow‐up period. By contrast, more treatment episodes were associated with an increased risk of overdose (OR 1.62). Other independent predictors of overdose over follow‐up were more extensive polydrug use (OR 1.40), and having overdosed in the year preceding the study (OR 7.87).
The definition of opioid‐related deaths in Australia: implications for surveillance and policy
Authors: JAUNCEY MARIANNE E. , TAYLOR LEE K. , DEGENHARDT LOUISA J.
Published: January 2006

The reported number of deaths caused by opioid use depends on the definition of an opioid‐related death. In this study, we used Australian Bureau of Statistics (ABS) mortality data to illustrate how choice of classification codes used to record cause of death can impact on the statistics reported for national surveillance of opioid deaths. Using International Classification of Diseases version 10 (ICD‐10) codes from ABS mortality data 1997–2002, we examined all deaths where opioids were reported as a contributing or underlying cause. For the 6‐year period there was a total of 5839 deaths where opioids were reported. Three possible surveillance definitions of accidental opioid‐related deaths were examined, and compared to the total number of deaths where opioids were reported for each year. Age restrictions, often placed on surveillance definitions, were also examined. As expected, the number of deaths was higher with the more inclusive definitions. Trends in deaths were found to be similar regardless of the definition used; however, a comparison between Australian states revealed up to a twofold difference in the absolute numbers of accidental opioid‐related deaths, depending on the definition. Any interpretation of reported numbers of opioid deaths should specify any restrictions placed on the data, and describe the implications of definitions used.
Characteristics of treatment provided for amphetamine use in New South Wales, Australia
Authors: McKETIN REBECCA , KELLY ERIN , INDIG DEVON
Published: January 2006

The purpose of this study was to examine the types of treatment services provided for amphetamine use, the characteristics of amphetamine treatment clients and the geographic areas most affected by amphetamine treatment provision within New South Wales (NSW), Australia. Data on completed amphetamine treatment episodes were extracted from the NSW Minimum Data Set for Alcohol and Other Drug Treatment Services for the year 2002/03 (n = 4337). The geographic area of treatment presentations was based on the location of the treatment service, and was categorized as metropolitan, regional or rural. Treatment disproportionately affected regional and rural NSW, and treatment clients often presented with concurrent cannabis and/or alcohol problems. Clients were overwhelmingly injecting drug users with poor socio‐demographic characteristics. Counselling was the most common treatment service provided, followed by detoxification and residential rehabilitation. Detoxification was usually provided in an in‐patient setting, particularly within metropolitan NSW. Compliance with residential rehabilitation was notably poor. In conclusion, the development of appropriate interventions for amphetamine use needs to consider that the majority of treatment recipients will be based in a regional or rural setting, and treating amphetamine users will often involve treatment of concurrent cannabis and alcohol problems. The nature and appropriateness of treatment services provided for amphetamine use needs to be reviewed in detail, and further research is needed into the nature of problematic amphetamine use and factors affecting treatment demand in regional and rural NSW.
Return to Smoking Following a Smoke‐Free Psychiatric Hospitalization
Authors: Prochaska Judith J. , Fletcher Lindsay , Hall Stephen E. , Hall Sharon M.
Published: January 2006

This study examined the smoking behaviors and motivations of 100 patients hospitalized in a smoke‐free psychiatry unit. The sample averaged nineteen cigarettes per day and had a history of repeated failed quit attempts, yet 65% expressed interest in quitting. During hospitalization, nicotine replacement was provided to 70% of smokers to manage nicotine withdrawal. Provider counseling for smoking cessation, however, was rare, and all patients returned to smoking within five weeks of hospital discharge. The inpatient setting provides a potential site for initiating tobacco dependence treatment; however to maintain abstinence following hospital discharge, greater support is needed.
The Effects of Alcohol and Drug Dependence on the Course of Depression
Authors: Agosti Vito , Levin Frances R.
Published: January 2006

There is a paucity of epidemiological data regarding the effects of substance use dependence (SUD) on the course of depression. This study analyzed data from the National Comorbidity Survey (NCS). Among respondents with lifetime SUD and unipolar depression, current SUD increased the risk (OR = 2.9) of past year depression and anxiety disorders (OR = 2.2).
Safety and Tolerability of N‐Acetylcysteine in Cocaine‐Dependent Individuals
Authors: LaRowe Steven D. , Mardikian Pascale , Malcolm Robert , Myrick Hugh , Kalivas Peter , McFarland Krista , Saladin Michael , McRae Aimee , Brady Kathleen
Published: January 2006

A double‐blind placebo‐controlled crossover Phase I trial was conducted to assess the safety and tolerability of N‐Acetylcysteine (NAC) in healthy, cocaine‐dependent humans. Thirteen participants attended a three‐day hospitalization in which they received placebo or NAC. Subjects were crossed over to receive the opposite medication condition during a second three‐day hospitalization, which occurred the following week. Across placebo and NAC conditions, only mild side effects were noted, and the number of subjects reporting side effects did not differ. There were trends for a greater reduction in withdrawal symptoms and craving within the NAC condition. These preliminary results suggest that NAC is well tolerated in healthy, cocaine‐dependent individuals and may reduce cocaine‐related withdrawal symptoms and craving.
On the importance of internalized consumption norms for ill health
Authors: Yngwe Monica Åberg , Lundberg Olle , Burström BO
Published: January 2006

Aim: Relative deprivation has in previous studies been put forward as a possible mechanism in the income and health relation. To capture the importance of social comparisons analytically has been problematic due to the difficulty in identifying reference groups of significance for the individual. The authors suggest that using the individual's own preferences, arguing these to be preferences of both society and reference groups internalized by the individual, may partly bridge this problem. Methods: The study is based on the Swedish Survey of Living Conditions 1998 including a list of 37 consumption items and activities. By counting the items that the individual cannot afford, but at the same time considers to be a necessity and something that all adults should afford, a measure of self-rated deprivation (SRD) is constructed. The outcome measure used is less than good self-rated health and limiting longstanding illness. Men and women aged 25—64 years are included. Results: Over the different groups of self-rated deprivation a clear gradient in ill health, for both health measures, was found among women. The results for men seemed to dichotomize between non-deprived and those deprived on at least one item. The logistic regression models showed that even after adjusting for socioeconomic group and cash margin, there was a significant effect of self-rated deprivation. Conclusions: A significant relation was found between self-rated deprivation and ill health, both less than good health and limiting longstanding illness. Self-rated deprivation had a stronger impact on women than men.
A dual-process account of digit invariance learning
Authors: Kelly Steve W. , Wilkin Katie
Published: January 2006

Performance in the McGeorge and Burton (1990) digit invariance task was originally thought to be mediated by unconscious abstraction of a “rule” that identified the invariant feature across all study items. Subsequent explanations have suggested explicit strategy use or similarity-to-exemplar matching rather than abstraction. This paper presents data that suggest that both similarity and abstraction can be used under different task demands. Delay between study and test afforded abstraction of the invariant knowledge whereas reducing the pool of study exemplars enhanced responding based on specific similarity. These results parallel effects found in the categorization literature. Rule abstraction in this sense may be due to statistical learning of feature frequency rather than abstraction of a central tendency or a complex/conceptual rule. Categorizing responses into subjective memory states (remember/know/guess) demonstrates that neither the similarity matching nor the abstraction mechanism uses information from episodic memory. Confidence measures show that participants are more confident of responses when the prototypical representation is used but not specific similarity. Taken together, these data suggest that abstracted knowledge is not held consciously but that participants have meta-awareness of when they are using the abstracted representation.
Disappearance of the budding yeast Bub2–Bfa1 complex from the mother-bound spindle pole contributes to mitotic exit
Authors: Fraschini Roberta , D'Ambrosio Claudio , Venturetti Marianna , Lucchini Giovanna , Piatti Simonetta
Published: January 2006

Budding yeast spindle position checkpoint is engaged by misoriented spindles and prevents mitotic exit by inhibiting the G protein Tem1 through the GTPase-activating protein (GAP) Bub2/Bfa1. Bub2 and Bfa1 are found on both duplicated spindle pole bodies until anaphase onset, when they disappear from the mother-bound spindle pole under unperturbed conditions. In contrast, when spindles are misoriented they remain symmetrically localized at both SPBs. Thus, symmetric localization of Bub2/Bfa1 might lead to inhibition of Tem1, which is also present at SPBs. Consistent with this hypothesis, we show that a Bub2 version symmetrically localized on both SPBs throughout the cell cycle prevents mitotic exit in mutant backgrounds that partially impair it. This effect is Bfa1 dependent and can be suppressed by high Tem1 levels. Bub2 removal from the mother-bound SPB requires its GAP activity, which in contrast appears to be dispensable for Tem1 inhibition. Moreover, it correlates with the passage of one spindle pole through the bud neck because it needs septin ring formation and bud neck kinases.
Evolution of a neuroprotective function of central nervous system myelin
Authors: Yin Xinghua , Baek Rena C. , Kirschner Daniel A. , Peterson Alan , Fujii Yasuhisa , Nave Klaus-Armin , Macklin Wendy B. , Trapp Bruce D.
Published: January 2006

The central nervous system (CNS) of terrestrial vertebrates underwent a prominent molecular change when a tetraspan membrane protein, myelin proteolipid protein (PLP), replaced the type I integral membrane protein, P0, as the major protein of myelin. To investigate possible reasons for this molecular switch, we genetically engineered mice to express P0 instead of PLP in CNS myelin. In the absence of PLP, the ancestral P0 provided a periodicity to mouse compact CNS myelin that was identical to mouse PNS myelin, where P0 is the major structural protein today. The PLP–P0 shift resulted in reduced myelin internode length, degeneration of myelinated axons, severe neurological disability, and a 50% reduction in lifespan. Mice with equal amounts of P0 and PLP in CNS myelin had a normal lifespan and no axonal degeneration. These data support the hypothesis that the P0–PLP shift during vertebrate evolution provided a vital neuroprotective function to myelin-forming CNS glia.
B cell–deficient NOD.H-2h4 mice have CD4+CD25+ T regulatory cells that inhibit the development of spontaneous autoimmune thyroiditis
Authors: Yu Shiguang , Maiti Prasanta K. , Dyson Melissa , Jain Renu , Braley-Mullen Helen
Published: January 2006

Wild-type (WT) NOD.H-2h4 mice develop spontaneous autoimmune thyroiditis (SAT) when given 0.05% NaI in their drinking water, whereas B cell–deficient NOD.H-2h4 mice are SAT resistant. To test the hypothesis that resistance of B cell–deficient mice to SAT was due to the activity of regulatory CD4+CD25+ T (T reg) cells activated if autoantigen was initially presented on non–B cells, CD25+ T reg cells were transiently depleted in vivo using anti-CD25. B cell–deficient NOD.H-2h4 mice given three weekly injections of anti-CD25 developed SAT 8 wk after NaI water. Thyroid lesions were similar to those in WT mice except there were no B cells in thyroid infiltrates. WT and B cell–deficient mice had similar numbers of CD4+CD25+Foxp3+ cells. Mice with transgenic nitrophenyl-specific B cells unable to secrete immunoglobulin were also resistant to SAT, and transient depletion of T reg cells resulted in severe SAT with both T and B cells in thyroid infiltrates. T reg cells that inhibit SAT were eliminated by day 3 thymectomy, indicating they belong to the subset of naturally occurring T reg cells. However, T reg cell depletion did not increase SAT severity in WT mice, suggesting that T reg cells may be nonfunctional when effector T cells are activated; i.e., by autoantigen-presenting B cells.
Essential role of the T cell–specific adapter protein in the activation of LCK in peripheral T cells
Authors: Marti Francesc , Garcia Gonzalo G. , Lapinski Philip E. , MacGregor Jennifer N. , King Philip D.
Published: January 2006

T cell–specific adapter protein (TSAd) is a SRC-homology-2 (SH2) domain–containing intracellular signaling molecule that is required for T cell antigen receptor (TCR)–induced cytokine synthesis in T cells. How TSAd functions in TCR signal transduction is not clear. Previous work has suggested a nuclear role for this adapter. However, other evidence suggests that TSAd also functions in the cytoplasm. Using T cells from TSAd-deficient mice, we now show that the major role of TSAd in the cytoplasm is in activation of the LCK protein tyrosine kinase at the outset of TCR signal transduction. Consequently, TSAd regulates several downstream signaling events, including intracellular calcium mobilization and activation of the Ras–extracellular signal–regulated kinase signaling pathway. TSAd regulates LCK activity directly through physical interaction with LCK SH3 and SH2 domains. These studies reveal TSAd as a positive regulator of proximal TCR signal transduction and provide important new information on the mechanism of TCR-induced LCK activation.
Block of C/EBPα function by phosphorylation in acute myeloid leukemia with FLT3 activating mutations
Authors: Radomska Hanna S. , Bassères Daniela S. , Zheng Rui , Zhang Pu , Dayaram Tajhal , Yamamoto Yukiya , Sternberg David W. , Lokker Nathalie , Giese Neill A. , Bohlander Stefan K. , Schnittger Susanne , Delmotte Marie-Hélène , Davis Roger J. , Small Donald , Hiddemann Wolfgang , Gilliland D. Gary , Tenen Daniel G.
Published: January 2006

Mutations constitutively activating FLT3 kinase are detected in ∼30% of acute myelogenous leukemia (AML) patients and affect downstream pathways such as extracellular signal–regulated kinase (ERK)1/2. We found that activation of FLT3 in human AML inhibits CCAAT/enhancer binding protein α (C/EBPα) function by ERK1/2-mediated phosphorylation, which may explain the differentiation block of leukemic blasts. In MV4;11 cells, pharmacological inhibition of either FLT3 or MEK1 leads to granulocytic differentiation. Differentiation of MV4;11 cells was also observed when C/EBPα mutated at serine 21 to alanine (S21A) was stably expressed. In contrast, there was no effect when serine 21 was mutated to aspartate (S21D), which mimics phosphorylation of C/EBPα. Thus, our results suggest that therapies targeting the MEK/ERK cascade or development of protein therapies based on transduction of constitutively active C/EBPα may prove effective in treatment of FLT3 mutant leukemias resistant to the FLT3 inhibitor therapies.
Structural Determinants for Functional Coupling Between the β and α Subunits in the Ca2+-activated K+ (BK) Channel
Authors: Orio Patricio , Torres Yolima , Rojas Patricio , Carvacho Ingrid , Garcia Maria L. , Toro Ligia , Valverde Miguel A. , Latorre Ramon
Published: January 2006

High conductance, calcium- and voltage-activated potassium (BK, MaxiK) channels are widely expressed in mammals. In some tissues, the biophysical properties of BK channels are highly affected by coexpression of regulatory (β) subunits. The most remarkable effects of β1 and β2 subunits are an increase of the calcium sensitivity and the slow down of channel kinetics. However, the detailed characteristics of channels formed by α and β1 or β2 are dissimilar, the most remarkable difference being a reduction of the voltage sensitivity in the presence of β1 but not β2. Here we reveal the molecular regions in these β subunits that determine their differential functional coupling with the pore-forming α-subunit. We made chimeric constructs between β1 and β2 subunits, and BK channels formed by α and chimeric β subunits were expressed in Xenopus laevis oocytes. The electrophysiological characteristics of the resulting channels were determined using the patch clamp technique. Chimeric exchange of the different regions of the β1 and β2 subunits demonstrates that the NH3 and COOH termini are the most relevant regions in defining the behavior of either subunit. This strongly suggests that the intracellular domains are crucial for the fine tuning of the effects of these β subunits. Moreover, the intracellular domains of β1 are responsible for the reduction of the BK channel voltage dependence. This agrees with previous studies that suggested the intracellular regions of the α-subunit to be the target of the modulation by the β1-subunit.
Activation Dependence of Stretch Activation in Mouse Skinned Myocardium: Implications for Ventricular Function
Authors: Stelzer Julian E. , Larsson Lars , Fitzsimons Daniel P. , Moss Richard L.
Published: January 2006

Recent evidence suggests that ventricular ejection is partly powered by a delayed development of force, i.e., stretch activation, in regions of the ventricular wall due to stretch resulting from torsional twist of the ventricle around the apex-to-base axis. Given the potential importance of stretch activation in cardiac function, we characterized the stretch activation response and its Ca2+ dependence in murine skinned myocardium at 22°C in solutions of varying Ca2+ concentrations. Stretch activation was induced by suddenly imposing a stretch of 0.5–2.5% of initial length to the isometrically contracting muscle and then holding the muscle at the new length. The force response to stretch was multiphasic: force initially increased in proportion to the amount of stretch, reached a peak, and then declined to a minimum before redeveloping to a new steady level. This last phase of the response is the delayed force characteristic of myocardial stretch activation and is presumably due to increased attachment of cross-bridges as a consequence of stretch. The amplitude and rate of stretch activation varied with Ca2+ concentration and more specifically with the level of isometric force prior to the stretch. Since myocardial force is regulated both by Ca2+ binding to troponin-C and cross-bridge binding to thin filaments, we explored the role of cross-bridge binding in the stretch activation response using NEM-S1, a strong-binding, non-force–generating derivative of myosin subfragment 1. NEM-S1 treatment at submaximal Ca2+-activated isometric forces significantly accelerated the rate of the stretch activation response and reduced its amplitude. These data show that the rate and amplitude of myocardial stretch activation vary with the level of activation and that stretch activation involves cooperative binding of cross-bridges to the thin filament. Such a mechanism would contribute to increased systolic ejection in response to increased delivery of activator Ca2+ during excitation–contraction coupling.
New methods in celestial mechanics and mission design
Authors: Marsden Jerrold , Ross Shane
Published: January 2006

The title of this paper is inspired by the work of Poincaré [1890, 1892], who introduced many key dynamical systems methods during his research on celestial mechanics and especially the three-body problem. Since then, many researchers have contributed to his legacy by developing and applying these methods to problems in celestial mechanics and, more recently, with the design of space missions. This paper will give a survey of some of these exciting ideas, and we would especially like to acknowledge the work of Michael Dellnitz, Frederic Gabern, Katalin Grubits, Oliver Junge, Wang-Sang Koon, François Lekien, Martin Lo, Sina Ober-Blöbaum, Kathrin Padberg, Robert Preis, and Bianca Thiere. One of the purposes of the AMS Current Events session is to discuss work of others. Even though we were involved in the research reported on here, this short paper is intended to survey many ideas due to our collaborators and others. This survey is by no means complete, and we apologize for not having time or space to do justice to many important and fundamental works. In fact, the results reported on here rely on and were inspired by important preceding work of many others in celestial mechanics, mission design and in dynamical systems. We mention just a few whose work had a positive influence on what is reported here: Brian Barden, Ed Belbruno, Robert Farquhar, Gerard Gómez, George Haller, Charles Jaffé, Kathleen Howell, Linda Petzold, Josep Masdemont, Vered Rom-Kedar, Radu Serban, Carles Simó, Turgay Uzer, Steve Wiggins, and Roby Wilson. In an upcoming monograph (see Koon, Lo, Marsden, and Ross [2005]), the dynamical systems and computational approach and its application to mission design are discussed in detail. One of the key ideas is that the competing gravitational pull between celestial bodies creates a vast array of passageways that wind around the Sun, planets and moons. The boundaries of these passageways are realized geometrically as invariant manifolds attached to equilibrium points and periodic orbits in interlinked three-body problems. In particular, tube-like structures form an interplanetary transport network which will facilitate the exploration of Mercury, the Moon, the asteroids, and the outer solar system, including a mission to assess the possibility of life on Jupiter’s icy moons. The use of these methods in problems in molecular dynamics of interest in chemistry is also briefly discussed.