bluuebunny/crossref_metadata_2025 huggingface dataset:
Diabetic Foot Complications: Diagnosis and Management
Authors: Giurini John M. , Lyons Thomas E.
Published: August 2005

Foot complications in patients with diabetes mellitus are a challenge to the health care industry. A great deal of expenditure is due to the management of diabetic foot complications. This places a great burden on the health care industry. It also places a great burden on those diabetic patients with foot complications and their families. Therefore, their effective management in an efficient manner is crucial to our patients. To deal with these problems, a dedicated, knowledgeable, and experienced multidisciplinary team is key. Intervention at the earliest possible time yields the best outcome. Prevention is the focus for those with no ulcerations. For those with ulcerations, prompt recognition and treatment is key. The importance of classifying ulcerations according to size, depth, presence or absence of infection, and vascular status can not be overstated. Proper offloading is vital for those with neuropathic lesions. Recognition of patients with a component of ischemia and vascular intervention to increase perfusion will aid in wound healing. Of course deep infection requires immediate drainage. All efforts of those in the multidisciplinary team are directed at the restoration and maintenance of an ulcer-free foot which is important in enabling our patients to maintain their ambulatory status.
The Charcot Foot: A Clinical Challenge
Authors: Stefansky Stacey A. , Rosenblum Barry I.
Published: August 2005

The Charcot foot (CF) is a clinical challenge. The CF occurs in the presence of sensory neuropathy; its etiology and pathogenesis are constantly debated. The aim of this short article is to examine therapeutic options from the perspective of experienced podiatrists.
Abnormalities of Vasomotor Regulation in the Pathogenesis of the Acute Charcot Foot of Diabetes Mellitus
Authors: Jeffcoate William J.
Published: August 2005

The acute Charcot foot complicates distal symmetrical neuropathy but is remarkably rare. This article reviews the multiple processes that may complicate both diabetes and neuropathy and might, in turn, explain the association of features that are typical of this disorder: osteolysis, vascular calcification in association with intact lower limb blood flow, and uncontrolled inflammation. Specifically, it is suggested that the disorder arises because of abnormal expression of the nuclear transcription factor, NFkappaB, in diabetic neuropathy and that this is further enhanced at the onset of the acute arthropathy as a result of the release of proinflammatory cytokines, such as tumor necrosis factor-α and interleukin-1. These proinflammatory cytokines and RANKL may then enter a cycle of mutual augmentation, and this is a factor that underlies the continuing inflammation that characterizes the disorder. If this hypothesis is confirmed, it would suggest the option of new effective treatments for this sometimes devastating disorder.
Up-regulated expression in nonhematopoietic tissues of the BCL2A1-derived minor histocompatibility antigens in response to inflammatory cytokines: relevance for allogeneic immunotherapy of leukemia
Authors: Kloosterboer Freke M. , van Luxemburg-Heijs Simone A. P. , van Soest Ronald A. , van Egmond H. M. Esther , Willemze Roel , Falkenburg J. H. Frederik
Published: August 2005

T cells directed against hematopoietic-restricted minor histocompatibility antigens (mHags) may mediate graft-versus-leukemia (GVL) reactivity without graft-versus-host disease (GVHD). Recently, the HLA-A24–restricted mHag ACC-1 and the HLA-B44–restricted mHag ACC-2 encoded by separate polymorphisms within the BCL2A1 gene were characterized. Hematopoietic-restricted expression was suggested for these mHags. We demonstrate BCL2-related protein A1 (BCL2A1) mRNA expression in mesenchymal stromal cells (MSCs) that was up-regulated by the inflammatory cytokines tumor necrosis factor α (TNF-α) and/or interferon γ (IFN-γ). Analysis of cytotoxicity and IFN-γ production illustrated that ACC-2–specific T cells did not recognize untreated MSCs or IFN-γ–treated MSCs but showed specific recognition and killing of MSCs treated with TNF-α plus IFN-γ. We hypothesize that under steady-state circumstances BCL2A1-specific T cells may exhibit relative specificity for hematopoietic tissue, but reactivity against nonhematopoietic cells may occur when inflammatory infiltrates are present. Thus, the role of BCL2A1-specific T cells in differential induction of GVL reactivity and GVHD may depend on the presence of inflammatory responses that may occur during GVHD.
Endogenous NGF regulates CGRP expression in human monocytes, and affects HLA-DR and CD86 expression and IL-10 production
Authors: Bracci-Laudiero Luisa , Aloe Luigi , Caroleo Maria Cristina , Buanne Pasquale , Costa Nicola , Starace Giuseppe , Lundeberg Thomas
Published: August 2005

Our recent results on autocrine nerve growth factor (NGF) synthesis in B lymphocytes, which directly regulates the expression and release of calcitonin gene-related peptide (CGRP), a neuropeptide known to down-regulate immune response, led us to propose an anti-inflammatory action of NGF. In the present work, we investigated whether the endogenous synthesis of NGF can regulate the expression of CGRP in other antigen-presenting cells, such as monocytes, and whether this may have a functional effect. Our data indicate that human monocytes synthesize basal levels of NGF and CGRP and that, following lipopolysaccharide (LPS) stimulation, NGF and CGRP expression are both up-regulated. When endogenous NGF is neutralized, the up-regulation of CGRP expression induced by LPS is inhibited. The expression of membrane molecules involved in T-cell activation such as human leukocyte antigen-DR (HLA-DR) and CD86 is affected by endogenous NGF, and similar effects were obtained using a CGRP1 receptor antagonist. In addition, NGF deprivation in LPS-treated monocytes significantly decreases interleukin 10 (IL-10) synthesis. Our findings indicate that endogenous NGF synthesis has a functional role and may represent a physiologic mechanism to down-regulate major histocompatibility complex (MHC) class II and CD86 expression and alter the development of immune responses.
A crucial role for T-bet in selectin ligand expression in T helper 1 (Th1) cells
Authors: Underhill Greg H. , Zisoulis Dimitrios G. , Kolli K. Pallav , Ellies Lesley G. , Marth Jamey D. , Kansas Geoffrey S.
Published: August 2005

Proinflammatory T helper 1 (Th1) cells express high levels of carbohydrate ligands for the endothelial selectins, but the molecular basis for this phenotype is incompletely understood. We document here a significant role in selectin ligand formation for the recently described Th1 transcription factor T-bet. Th1 cells generated from T-bet-/- mice showed significantly lower levels of ligands for both E-selectin and P-selectin, compared with wild-type (WT) Th1 cells. Enforced expression of T-bet in WT Th0 cells only modestly up-regulated P-selectin ligands and had no effect on E-selectin ligands. To define a mechanism for the defects observed in T-bet-/- mice, we examined expression of glycosyltransferases involved in selectin ligand biosynthesis. T-bet-/- Th1 cells expressed significantly lower levels of core 2 β1,6 N-acetylglucosaminyltransferase I (C2GlcNAcT-I), but no differences in levels of α 2,3-sialyltransferase IV (ST3Gal-IV). Further, we show that T-bet is responsible for the signal transducer and activator of transcription 4 (Stat4)–independent increase in Th1 cells of fucosyltransferase VII (FucT-VII). We also identify ST3Gal-VI, which is thought to play an important role in E- and P-selectin ligand formation, as an interleukin 12 (IL-12)–regulated, T-bet–dependent gene. These data show that T-bet controls selectin ligand formation in Th1 cells via control of expression of multiple key enzymes in response to IL-12 signaling and establishes an independent transcriptional pathway for control of Th1 cell traffic.
Secretion of IFN-γ and not IL-2 by anergic human T cells correlates with assembly of an immature immune synapse
Authors: Carlin Leo M. , Yanagi Kumiko , Verhoef Adrienne , Hoen Esther N. M. Nolte-'t , Yates John , Gardner Leanne , Lamb Jonathan , Lombardi Giovanna , Dallman Margaret J. , Davis Daniel M.
Published: August 2005

We report differences in the supramolecular organization of the immunologic synapse (IS) formed by resting and anergic human T cells with agonist peptide-loaded antigen-presenting cells (APCs). T cells reactive to influenza A hemagglutinin peptide or Fel d 1 peptide 4 were rendered both anergic and regulatory by incubation with high doses of agonist peptide in the absence of APCs. At the IS between resting T cells and peptide-loaded APCs, both CD3ϵ and CD3ζ initially accumulate within a ring or arc before redistributing within 30 minutes to single or multiple foci more central to the contact. In contrast, at synapses formed by anergized T cells, CD3ϵ and CD3ζ remained organized within an arc or ring and failed to redistribute centrally. However, intercellular communication between anergic human T cells and agonist peptide-loaded APCs was not a null event, since it triggered secretion of T-cell interferon γ (IFN-γ) but not, for example, interleukin 2 (IL-2). Thus, distinct organizations of CD3 at the T-cell IS correlate with different cytokine profiles; the mature IS formed by resting T cells correlates with their production of both IFN-γ and IL-2, whereas the immature IS formed by anergic T cells seems able to facilitate IFN-γ but not IL-2 production.
Risk factors and kinetics of thrombocytopenia associated with bortezomib for relapsed, refractory multiple myeloma
Authors: Lonial Sagar , Waller Edmund K. , Richardson Paul G. , Jagannath Sundar , Orlowski Robert Z. , Giver Cynthia R. , Jaye David L. , Francis Dixil , Giusti Sara , Torre Claire , Barlogie Bart , Berenson James R. , Singhal Seema , Schenkein David P. , Esseltine Dixie-Lee W. , Anderson Jessica , Xiao Hugh , Heffner Leonard T. , Anderson Kenneth C. ,   for the SUMMIT/CREST Investigators
Published: August 2005

Bortezomib, a proteasome inhibitor with efficacy in multiple myeloma, is associated with thrombocytopenia, the cause and kinetics of which are different from those of standard cytotoxic agents. We assessed the frequency, kinetics, and mechanism of thrombocytopenia following treatment with bortezomib 1.3 mg/m2 in 228 patients with relapsed and/or refractory myeloma in 2 phase 2 trials. The mean platelet count decreased by approximately 60% during treatment but recovered rapidly between treatments in a cyclic fashion. Among responders, the pretreatment platelet count increased significantly during subsequent cycles of therapy. The mean percent reduction in platelets was independent of baseline platelet count, M-protein concentration, and marrow plasmacytosis. Plasma thrombopoietin levels inversely correlated with platelet count. Murine studies demonstrated a reduction in peripheral platelet count following a single bortezomib dose without negative effects on megakaryocytic cellularity, ploidy, or morphology. These data suggest that bortezomib-induced thrombocytopenia is due to a reversible effect on megakaryocytic function rather than a direct cytotoxic effect on megakaryocytes or their progenitors. The exact mechanism underlying bortezomib-induced thrombocytopenia remains unknown but it is unlikely to be related to marrow injury or decreased thrombopoietin production.
PALSSE: A program to delineate linear secondary structural elements from protein structures
Authors: Majumdar Indraneel , Krishna S Sri , Grishin Nick V
Published: August 2005

Background

The majority of residues in protein structures are involved in the formation of α-helices and β-strands. These distinctive secondary structure patterns can be used to represent a protein for visual inspection and in vector-based protein structure comparison. Success of such structural comparison methods depends crucially on the accurate identification and delineation of secondary structure elements.

Results

We have developed a method PALSSE (Predictive Assignment of Linear Secondary Structure Elements) that delineates secondary structure elements (SSEs) from protein Cα coordinates and specifically addresses the requirements of vector-based protein similarity searches. Our program identifies two types of secondary structures: helix and β-strand, typically those that can be well approximated by vectors. In contrast to traditional secondary structure algorithms, which identify a secondary structure state for every residue in a protein chain, our program attributes residues to linear SSEs. Consecutive elements may overlap, thus allowing residues located at the overlapping region to have more than one secondary structure type.

Conclusion

PALSSE is predictive in nature and can assign about 80% of the protein chain to SSEs as compared to 53% by DSSP and 57% by P-SEA. Such a generous assignment ensures almost every residue is part of an element and is used in structural comparisons. Our results are in agreement with human judgment and DSSP. The method is robust to coordinate errors and can be used to define SSEs even in poorly refined and low-resolution structures. The program and results are available at http://prodata.swmed.edu/palsse/.
A screen for proteins that interact with PAX6: C-terminal mutations disrupt interaction with HOMER3, DNCL1 and TRIM11
Authors: Cooper Simon T , Hanson Isabel M
Published: August 2005

Background

The PAX6 protein is a transcriptional regulator with a key role in ocular and neurological development. Individuals with heterozygous loss-of-function mutations in the PAX6 gene have malformations of the eye and brain. Little is known about the interactions of PAX6 with other proteins, so we carried out a systematic screen for proteins that interact with PAX6.

Results

We used bioinformatics techniques to characterise a highly conserved peptide at the C-terminus of the PAX6 protein. Yeast two-hybrid library screens were then carried out to identify brain-expressed proteins that interact with the C-terminal peptide and with the entire PAX6 proline-serine-threonine-rich domain. Three novel PAX6-interacting proteins were identified: the post-synaptic density (PSD) protein HOMER3, the dynein subunit DNCL1, and the tripartite motif protein TRIM11. Three C-terminal PAX6 mutations, previously identified in patients with eye malformations, all reduced or abolished the interactions.

Conclusion

Our preliminary data suggest that PAX6 interacts with HOMER3, DNCL1 and TRIM11. We propose that the interaction of PAX6 with HOMER3 and DNCL1 is a mechanism by which synaptic activation could lead to changes in neuronal transcriptional activity, and that some of the neural anomalies in patients with PAX6 mutations could be explained by impaired protein-protein interactions.
Suicidal tendencies and attitude towards freedom to choose suicide among Lithuanian schoolchildren: results from three cross-sectional studies in 1994, 1998, and 2002
Authors: Zemaitiene Nida , Zaborskis Apolinaras
Published: August 2005

Background

Suicidal behaviour is increasingly becoming a phenomenon associated with young people and an important public health issue in Lithuania. However, there are very few studies evaluating impact of young peoples' attitudes towards suicide to their suicidal behaviour. A better understanding of the relations among the variables associated with suicidal ideation and threats in the normal population of adolescents may eventually result in a better understanding of the more serious forms of adolescent suicidal behaviour. The aim of the present study was to evaluate prevalence of suicidal tendencies among Lithuanian schoolchildren and to estimate its association with an attitude towards suicide in 1994 – 2002.

Methods

Three country representative samples of schoolchildren, aged 11, 13 and 15, were surveyed in 1994 (n = 5428), 1998 (n = 4513), and 2002 (n = 5645) anonymously in conformity with the methodology of the World Health Organization Cross – National study on Health Behaviour in School-aged Children (HBSC).

Results

About one third of respondents reported about suicidal ideation, plans or attempts to commit suicide. In the study period of eight years, the percentage of adolescents who reported sometime suicidal ideation decreased but the percentage of adolescents who declared serious suicidal behaviour remained on the same high level (8.1%, 9.8% and 8.4% correspondingly in 1994, 1998 and 2002). Moreover, the number of suicidal attempts changed from 1.0% in 1994 to 1.8% in the year 1998 and to 1,7% in the year 2002. The schoolchildren's attitude towards suicide became more agreeable: 36.6%, 41.9% and 62.5% of respondents, correspondingly in 1994, 1998 and 2002, answered that they agree with a person's freedom to make a choice between life and suicide. A multiple logistic regression analysis with low level of suicidality and high level of suicidality versus non suicidal behaviour as dependent variables for gender, age, year of the survey and attitude towards freedom to choose suicide as independent variables approved a significant association between studied covariates over the entire study period.

Conclusion

Suicidal tendencies are quite frequent among Lithuanian adolescents. An increasing number of schoolchildren are expressing an agreeable attitude towards suicide. The approving attitude towards suicide among adolescents correlates with suicidal ideation and behaviour.
Pretest probability assessment derived from attribute matching
Authors: Kline Jeffrey A , Johnson Charles L , Pollack Charles V , Diercks Deborah B , Hollander Judd E , Newgard Craig D , Garvey J Lee
Published: August 2005

Background

Pretest probability (PTP) assessment plays a central role in diagnosis. This report compares a novel attribute-matching method to generate a PTP for acute coronary syndrome (ACS). We compare the new method with a validated logistic regression equation (LRE).

Methods

Eight clinical variables (attributes) were chosen by classification and regression tree analysis of a prospectively collected reference database of 14,796 emergency department (ED) patients evaluated for possible ACS. For attribute matching, a computer program identifies patients within the database who have the exact profile defined by clinician input of the eight attributes. The novel method was compared with the LRE for ability to produce PTP estimation <2% in a validation set of 8,120 patients evaluated for possible ACS and did not have ST segment elevation on ECG. 1,061 patients were excluded prior to validation analysis because of ST-segment elevation (713), missing data (77) or being lost to follow-up (271).

Results

In the validation set, attribute matching produced 267 unique PTP estimates [median PTP value 6%, 1st–3rd quartile 1–10%] compared with the LRE, which produced 96 unique PTP estimates [median 24%, 1st–3rd quartile 10–30%]. The areas under the receiver operating characteristic curves were 0.74 (95% CI 0.65 to 0.82) for the attribute matching curve and 0.68 (95% CI 0.62 to 0.77) for LRE.

The attribute matching system categorized 1,670 (24%, 95% CI = 23–25%) patients as having a PTP < 2.0%; 28 developed ACS (1.7% 95% CI = 1.1–2.4%). The LRE categorized 244 (4%, 95% CI = 3–4%) with PTP < 2.0%; four developed ACS (1.6%, 95% CI = 0.4–4.1%).

Conclusion

Attribute matching estimated a very low PTP for ACS in a significantly larger proportion of ED patients compared with a validated LRE.
Assessing poisoning risks related to storage of household hazardous materials: using a focus group to improve a survey questionnaire
Authors: Kaufman Martin M , Smolinske Susan , Keswick David
Published: August 2005

Background

In fall of 2004, the authors began an investigation to characterize the correlations between the storage of Household Hazardous Materials and the associated health risks, particularly to children. The study area selected was Genesee County, Michigan, near Flint, with data to be collected by a phone survey of residents and through the acquisition of county hospital records containing procedure codes indicating treatment for poison emergencies, and review of poison control center data.

Methods

A focus group was used to identify key topics and relationships within these data for improving the phone survey questionnaire and its analysis.

Results

The focus group was successful in identifying the key issues with respect to all the data collection objectives, resulting in a significantly shorter and more topically focused survey questionnaire. Execution time of the phone survey decreased from 30 to 12 minutes, and useful relationships between the data were revealed, e.g., the linkage between reading food labels and reading labels on containers containing potentially harmful substances.

Conclusion

Focus groups and their preparatory planning can help reveal data interrelationships before larger surveys are undertaken. Even where time and budget constraints prevent the ability to conduct a series of focus groups, one successful focus group session can improve survey performance and reduce costs.
Prevalence of ultrasonography proved polycystic ovaries in North Indian women with type 2 diabetes mellitus
Authors: Zargar Abdul H , Gupta Vipin K , Wani Arshad I , Masoodi Shariq R , Bashir Mir I , Laway Bashir A , Ganie Mohammad A , Salahuddin Mohammad
Published: August 2005

Background

Polycystic ovaries (PCO) and their clinical expression (the polycystic ovary syndrome [PCOS]) as well as type 2 diabetes mellitus (T2DM) are common medical conditions linked through insulin resistance. We studied the prevalence of PCO and PCOS in women with diet and/or oral hypoglycemic treated T2DM and non-diabetic control women.

Design

Prospective study.

Methods

One hundred and five reproductive age group women with diet and /or oral hypoglycemic treated T2DM were the subjects of the study. Sixty age-matched non-diabetic women served as controls. Transabdominal ultrasonographic assessment of the ovaries was used to diagnose PCO. Clinical, biochemical and hormonal parameters were also noted.

Results

Ultrasonographic prevalence of PCO was higher in women with diabetes than in non-diabetic subjects (61.0% vs. 36.7%, P < 0.003) whereas that of PCOS was 37.1% in diabetic subjects and 25% in non-diabetic controls (P > 0.1). Diabetic women with PCO had diabetes of significantly longer duration than those without PCO (4.19±2.0 versus 2.9±1.6 yrs; p < 0.05). Among both diabetic and non-diabetic women, those with PCO had significantly higher plasma LH, LH/FSH ratio, total testosterone and androstenedione levels.

Conclusion

This study demonstrates a higher prevalence of PCO in women with T2DM as compared to non-diabetic subjects.
Three subsets of sequence complexity and their relevance to biopolymeric information
Authors: Abel David L , Trevors Jack T
Published: August 2005

Genetic algorithms instruct sophisticated biological organization. Three qualitative kinds of sequence complexity exist: random (RSC), ordered (OSC), and functional (FSC). FSC alone provides algorithmic instruction. Random and Ordered Sequence Complexities lie at opposite ends of the same bi-directional sequence complexity vector. Randomness in sequence space is defined by a lack of Kolmogorov algorithmic compressibility. A sequence is compressible because it contains redundant order and patterns. Law-like cause-and-effect determinism produces highly compressible order. Such forced ordering precludes both information retention and freedom of selection so critical to algorithmic programming and control. Functional Sequence Complexity requires this added programming dimension of uncoerced selection at successive decision nodes in the string. Shannon information theory measures the relative degrees of RSC and OSC. Shannon information theory cannot measure FSC. FSC is invariably associated with all forms of complex biofunction, including biochemical pathways, cycles, positive and negative feedback regulation, and homeostatic metabolism. The algorithmic programming of FSC, not merely its aperiodicity, accounts for biological organization. No empirical evidence exists of either RSC of OSC ever having produced a single instance of sophisticated biological organization. Organization invariably manifests FSC rather than successive random events (RSC) or low-informational self-ordering phenomena (OSC).
Selective Androgen Receptor Modulator Treatment Improves Muscle Strength and Body Composition and Prevents Bone Loss in Orchidectomized Rats
Authors: Gao Wenqing , Reiser Peter J. , Coss Christopher C. , Phelps Mitch A. , Kearbey Jeffrey D. , Miller Duane D. , Dalton James T.
Published: August 2005

The partial agonist activity of a selective androgen receptor modulator (SARM) in the prostate was demonstrated in orchidectomized rats. In the current study, we characterized the full agonist activity of S-3-(4-acetylamino-phenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-propionamide (a structurally related SARM referred to in other publications and hereafter as S-4) in skeletal muscle, bone, and pituitary of castrated male rats. Twelve weeks after castration, animals were treated with S-4 (3 or 10 mg/kg), dihydrotestosterone (DHT) (3 mg/kg), or vehicle for 8 wk. S-4 (3 and 10 mg/kg) restored soleus muscle mass and strength and levator ani muscle mass to that seen in intact animals. Similar changes were also observed in DHT-treated (3 mg/kg) animals. Compared with the anabolic effects observed in muscle, DHT (3 mg/kg) stimulated prostate and seminal vesicle weights moire than 2-fold greater than that observed in intact controls, whereas S-4 (3 mg/kg) returned these androgenic organs to only 16 and 17%, respectively, of the control levels. S-4 (3 and 10 mg/kg) and DHT (3 mg/kg) restored castration-induced loss in lean body mass. Furthermore, S-4 treatment caused a significantly larger increase in total body bone mineral density than DHT. S-4 (3 and 10 mg/kg) also demonstrated agonist activity in the pituitary and significantly decreased plasma LH and FSH levels in castrated animals in a dose-dependent manner. In summary, the strong anabolic effects of S-4 in skeletal muscle, bone, and pituitary were achieved with minimal pharmacologic effect in the prostate. The tissue-selective pharmacologic activity of SARMs provides obvious advantages over steroidal androgen therapy and demonstrates the promising therapeutic utility that this new class of drugs may hold.
Syntaxin 4 Facilitates Biphasic Glucose-Stimulated Insulin Secretion from Pancreatic β-Cells
Authors: Spurlin Beth A. , Thurmond Debbie C.
Published: August 2005

Numerous overexpression studies have recently implicated Syntaxin 4 as an effector of insulin secretion, although its requirement in insulin granule exocytosis is unknown. To address this, islets from Syntaxin 4 heterozygous (−/+) knockout mice were isolated and compared with islets from wild-type mice. Under static incubation conditions, Syntaxin 4 (−/+) islets showed a 60% reduction in glucose-stimulated insulin secretion compared with wild-type islets. Perifusion analyses revealed that Syntaxin 4 (−/+) islets secreted 50% less insulin during the first phase of glucose-stimulated insulin secretion and that this defect could be fully restored by the specific replenishment of recombinant Syntaxin 4. This essential role for Syntaxin 4 in secretion from the islet was localized to the β-cells because small interfering RNA-mediated depletion of Syntaxin 4 in MIN6 β-cells abolished glucose-stimulated insulin secretion. Moreover, immunofluorescent confocal microscopy revealed that Syntaxin 4 was principally localized to the β-cells and not the α-cells of the mouse islet. Remarkably, islets isolated from transgenic mice that express 2.4-fold higher levels of Syntaxin 4 relative to wild-type mice secreted approximately 35% more insulin during both phases of insulin secretion, suggesting that increased Syntaxin 4 may be beneficial for enhancing biphasic insulin secretion in a regulated manner. Taken together, these data support the notion that Syntaxin 4-based SNARE complexes are essential for biphasic insulin granule fusion in pancreatic β-cells.
Megalin Is a Receptor for Apolipoprotein M, and Kidney-Specific Megalin-Deficiency Confers Urinary Excretion of Apolipoprotein M
Authors: Faber Kirsten , Hvidberg Vibeke , Moestrup Søren K. , Dahlbäck Björn , Nielsen Lars Bo
Published: August 2005

Apolipoprotein (apo) M is a novel apolipoprotein belonging to the lipocalin protein superfamily, i.e. proteins binding small lipophilic compounds. Like other apolipoproteins, it is expressed in hepatocytes and secreted into plasma where it associates with high-density lipoprotein particles. In addition, apoM is expressed at high levels in the kidney tubule cells. In this study, we show that the multiligand receptor megalin, which is expressed in kidney proximal tubule cells, is a receptor for apoM and mediates its uptake in the kidney. To examine apoM binding to megalin, a recombinant apoM was expressed in Escherichia coli and used in surface plasmon resonance and cell culture studies. The results showed apoM binding to immobilized megalin [dissociation constant (Kd) ∼ 0.3–1 μm] and that the apoM was endocytosed by cultured rat yolk sac cells in a megalin-dependent manner. To examine the importance of apoM binding by megalin in vivo, we analyzed mice with a tissue-specific deficiency of megalin in the kidney. Megalin deficiency was associated with pronounced urinary excretion of apoM, whereas apoM was not detected in normal mouse, human, or rat urine. Gel filtration analysis showed that the urinary apoM-containing particles were small and devoid of apoA-I. The results suggest that apoM binds to megalin and that megalin-mediated endocytosis in kidney proximal tubules prevents apoM excretion in the urine.
Intentions to use hormonal male contraception: The role of message framing, attitudes and stress appraisals
Authors: O'Connor Daryl B. , Ferguson Eamonn , O'Connor Rory C.
Published: August 2005

Two studies are reported. Study one (N = 104) explored the extent to which male hormonal contraception is perceived as risky compared to other prevention behaviours. Study two examined the effects of message framing on intentions to use hormonal male contraception and investigated whether attitude moderates message framing effects. Three hundred and four participants read either a loss frame or gain frame message and then completed questionnaires assessing their intentions to use hormonal male contraception, stress appraisals and the theory of planned behaviour (TPB) variables. Exposure to a loss frame influenced intention to use the daily male pill in men with a more postive attitude. This suggests that attitude, but not other TPB variables or stress appraisals have the capacity to moderate framing effects. Stress appraisals, in addition to TPB variables, significantly predicted variance in behavioural intentions in men and women. These findings are discussed within the context of Prospect Theory, perceived risk and prevention/detection behaviours.
Measurement of Midregional Proadrenomedullin in Plasma with an Immunoluminometric Assay
Authors: Morgenthaler Nils G , Struck Joachim , Alonso Christine , Bergmann Andreas
Published: August 2005

Background: Adrenomedullin (ADM) is a potent vasodilatory peptide, and circulating concentrations have been described for several disease states, including dysfunction of the cardiovascular system and sepsis. Reliable quantification has been hampered by the short half-life, the existence of a binding protein, and physical properties. Here we report the technical evaluation of an assay for midregional pro-ADM (MR-proADM) that does not have these problems.

Methods: MR-proADM was measured in a sandwich immunoluminometric assay using 2 polyclonal antibodies to amino acids 45–92 of proADM. The reference interval was defined in EDTA plasma of 264 healthy individuals (117 male, 147 female), and increased MR-proADM concentrations were found in 95 patients with sepsis and 54 patients with cardiovascular disease.

Results: The assay has an analytical detection limit of 0.08 nmol/L, and the interassay CV was <20% for values >0.12 nmol/L. The assay was linear on dilution with undisturbed recovery of the analyte. EDTA-, heparin-, and citrate-plasma samples were stable (<20% loss of analyte) for at least 3 days at room temperature, 14 days at 4 °C, and 1 year at −20 °C. MR-proADM values followed a gaussian distribution in healthy individuals with a mean (SD) of 0.33 (0.07) nmol/L (range, 0.10–0.64 nmol/L), without significant difference between males or females. The correlation coefficient for MR-proADM vs age was 0.50 (P <0.001). MR-proADM was significantly (P <0.001) increased in patients with cardiovascular disease [median (range), 0.56 (0.08–3.9) nmol/L] and patients with sepsis [3.7 (0.72–25.4) nmol/L].

Conclusions: MR-proADM is stable in plasma of healthy individuals and patients. MR-proADM measurements may be useful for evaluating patients with sepsis, systemic inflammation, or heart failure.
Effects of Sarin on the Nervous System of Subway Workers Seven Years after the Tokyo Subway Sarin Attack
Authors: Miyaki Koichi , Nishiwaki Yuji , Maekawa Kazuhiko , Ogawa Yasutaka , Asukai Nozomu , Yoshimura Kimio , Etoh Norihito , Matsumoto Yukio , Kikuchi Yuriko , Kumagai Nami , Omae Kazuyuki
Published: August 2005

Effects of Sarin on the Nervous System of Subway Workers Seven Years after the Tokyo Subway Sarin Attack: Koichi Miyaki, et al. Department of Preventive Medicine and Public Health, School of Medicine, Keio University—This study was designed to assess the after effects of sarin exposure on the nervous system in victims of the Tokyo Subway Sarin Attack, which occurred on 20 March, 1995. We performed a similar study 3 yr after the disaster. This time, we newly enrolled 36 staff of the Teito Rapid Transit Authority (Tokyo Eidan subway) to assess the 7 yr after effects on the nervous system, and merged previous data including unpublished data to enhance statistical power. New subjects consisted of 23 male exposed subjects and 13 referent subjects matched for age and working types. Neurobehavioral tests for psychomotor function and memory, stabilometry, and Benton visual retention test were performed. As reported previously, the exposed group performed significantly less well in the psychomotor function test (tapping) than the referent group (117.8±1.2 vs. 105.6 ± 1.2 msec). Using merged data, this phenomenon was also observed in a dose‐dependent manner and the exposed group performed significantly less well in the backward digit span test (4.47 ± 1.17 vs. 5.11 ± 1.65 digits). These results indicate that chronic decline of psychomotor function and memory function still exist 7 yr after the sarin exposure.
Knowledge, Attitude and Practice Regarding Organic Solvents among Printing Workers in Hong Kong
Authors: Yu Ignatius Tak‐Sun , Lee Nga Lan , Wong Tze Wai
Published: August 2005

Knowledge, Attitude and Practice Regarding Organic Solvents among Printing Workers in Hong Kong: Ignatius Tak‐Sun YU, et al. Department of Community & Family Medicine, The Chinese University of Hong Kong, China—To find out the prevalence of good knowledge, appropriate attitude and safe practice among printing workers exposed to organic solvents in Hong Kong, and to see if safe practice was influenced by the knowledge of and the attitude towards the harmful effects of organic solvents as well as other factors. The survey was conducted in a sample of 501 male printing workers from 28 factories in Hong Kong. The knowledge of and attitude towards the harmful effects of organic solvents, as well as the good practices adopted by the workers when handling solvents were explored using a questionnaire. Multiple logistic regression analysis was conducted to identify the major factors that influenced the knowledge, attitude and practice of workers. The prevalence of good knowledge, appropriate attitude and safe practice was low, being 20.4%, 38.4% and 22.0% respectively. Good knowledge was positively associated with awareness of the relevant legislation and past drinking behavior and negatively associated with current smoking. Appropriate attitude depended on having good knowledge and younger age. Safe practice did not depend on knowledge and attitude, but was positively associated with being informed of safety precautions and being supplied with chemical information by supervisors. The majority of workers believed that their employers, the Government and other statutory bodies should be responsible for providing information on chemicals, but very few of them actually obtained information from these sources. More workers preferred publications and talks rather than television as the means of obtaining further knowledge on chemicals. Front line supervisors have a pivotal role to play in improving safe practices of workers by informing them of the necessary precautions and supplying the relevant chemical information.
Multiple Endocrine Neoplasia Type 2A in a Kindred With C634Y Mutation
Authors: Jackson Malaka B. , Guttenberg Marta , Hedrick Holly , Moshang Thomas
Published: August 2005

Multiple endocrine neoplasia type 2A (MEN 2A) is most frequently caused by codon 634 activating mutations. Medullary thyroid carcinoma has occurred before the age of 2, with pheochromocytomas and primary hyperparathyroidism occurring later in childhood. We report cases of 4 siblings with C634Y-positive MEN 2A (all <11 years old): 3 with medullary thyroid carcinoma (1 had nodal metastasis, and another had a parathyroid adenoma) and 1 with C-cell hyperplasia.
Non-equilibrium Microstructure and Thermal Stability of Plasma-sprayed Al–Si Coatings
Authors: Baik K.H. , Seok H.K. , Kim H.S. , Grant P.S.
Published: August 2005

A splat-quenched, thick Al–Si deposit was manufactured by low-pressure plasma spraying (LPPS) and investigated in terms of microstructural inhomogeneity, Si solid solubility in α–Al, formation of metastable phases, and thermal stability. The LPPS Al–Si deposit had an inhomogeneous, layered microstructure consisting of splat-quenched lamellae and the incorporation of unmelted or partially melted particles. The splat-quenched Al–Si lamellae were formed by deposition of a fully liquid droplet and had an almost featureless microstructure at relatively low magnifications. There was a significant reduction in the α–Al lattice parameter in the LPPS Al–Si deposit because of extended Si solubility in the α–Al matrix. Transmission electron microscopy investigations showed that the splat quenching of liquid Al–Si droplet led to (i) columnar grain growth of α–Al(Si), (ii) formation of nano-sized Si precipitates in the Al matrix which was supersaturated with Si; and (iii) formation of amorphous Si phase embedded in the crystalline Al matrix. On reheating, the amorphous Si transformed into fine crystalline Si by interdiffusion of Al and Si atoms. Simultaneously, Si precipitation occurred in the supersaturated α–Al matrix. The overall activation energy for the Si crystallization/precipitation was estimated as ∼81 kJ/mol from a modified Kissinger analysis.
Microchannel Molding: A Soft Lithography-inspired Approach to Micrometer-scale Patterning
Authors: Martin Christopher R. , Aksay Ilhan A.
Published: August 2005

A new patterning technique for the deposition of sol-gels and chemical solution precursors was developed to address some of the limitations of soft lithography approaches. When using micromolding in capillaries to pattern precursors that exhibit large amounts of shrinkage during drying, topographical distortions develop. In place of patterning the elastomeric mold, the network of capillary channels was patterned directly into the substrate surface and an elastomer membrane is used to complete the channels. When the wetting properties of the substrate surfaces were carefully controlled using self-assembled monolayers (SAMs), lead zirconate titanate thin films with nearly rectangular cross-sections were successfully patterned. This technique, called microchannel molding (μCM), also provided a method for aligning multiple layers such as bottom electrodes for device fabrication.
Comparative Study of Microstructural Properties for YBa2Cu3O7 Films on Single-crystal and Ni-based Metal Substrates
Authors: Lin Y. , Wang H. , Maiorov B. , Hawley M.E. , Wetteland C.J. , Arendt P.N. , Foltyn S.R. , Civale L. , Jia Q.X.
Published: August 2005

We conducted a comparative study of microstructural properties for YBa2Cu3O7 (YBCO) films on single-crystal MgO and polycrystalline Ni-based metal substrates with ion-beam-assisted deposited (IBAD) MgO as a template. The film grown on the metal substrate shows more crystalline imperfections with density of screw dislocations four times higher than that of the film on single-crystal MgO, as revealed by high-resolution x-ray diffraction (HRXRD). These high-density screw dislocation cores connect well and form bigger clustered grains as detected by scanning tunneling microscopy. Transmission electron microscopy studies confirm that the structural quality of YBCO on the Ni-based alloy is comparable to that on single-crystal MgO. All these factors contribute to our routine fabrication of high-quality YBCO films on metal substrates with critical current densities in self-field as high as those for the films grown on single-crystal MgO substrates. Superconducting properties in fields are also discussed.
Benefits of Mild Wet Milling of the Intermediates for the Synthesis of Phase-pure Z-type Hexaferrite
Authors: Temuujin Jadambaa , Aoyama Masami , Senna Mamoru , Masuko Taisuke , Ando Chie , Kishi Hiroshi
Published: August 2005

A comparative study on the wet and dry milling of the intermediates for the Z-type hexagonal ferrite (Ba3Co2Fe24O41, Z phase) was performed. Phase-pure Z phase was synthesized by wet milling the intermediates comprising M and Y-type hexaferrites. The intermediates were obtained by calcining the stoichiometric powder mixture at 1080 °C. Subsequent wet milling by a planetary mill for 1 h increased the crystallization rate of Z phase upon subsequent heating at 1230 °C. In contrast, dry milling the intermediates resulted in the severe surface amorphization and led to heterogeneous crystalline states. The observed favorable effect of wet milling the intermediates was explained by the particle size reduction for the decrease of diffusion distance while preserving the basic layer units common to the related hexaferrites.
Synthesis of Water-soluble Silicon Oxide Material by Sol-gel Reaction in Tetraalkoxysilane-aminoalkyltrialkoxysilane Binary System
Authors: Kaneko Yoshiro , Iyi Nobuo , Matsumoto Taki , Usami Hisanao
Published: August 2005

A series of water-soluble silicon oxide materials was synthesized by the sol-gel reaction of tetramethoxysilane (TMOS)/3-aminopropyltrimethoxysilane (APTMOS) mixtures catalyzed by hydrochloric acid with varying TMOS/APTMOS ratios. Increase in TMOS composition made the products less water-soluble, and the richest TMOS composition for the water-soluble silicon oxide materials was found to be TMOS/APTMOS = 7/3 (mol/mol). Ultraviolet-visible spectroscopy of a 10 wt% aqueous solution of the product with TMOS/APTMOS = 7/3 showed a high transmittance in the visible region. Its infrared spectrum showed an absorptionband attributable to the Si–O bond, and the 29Si dipole decoupled/magic angle spinning–nuclear magnetic resonance spectrum exhibited signals in the regions of T3, Q3, and Q4, indicating a dense siloxane network structure. A peak due to an ordered structure with a 1.76 nm periodicity was observed in the x-ray diffraction profile, and a stripe pattern was observed in the transmission electron microscopy image. These results indicate that the rodlike silicon oxide macromolecules with a 1–2-nm diameter stack parallel. Thus a silicon oxide material with nano-ordered structure was successfully formed and such a structure produced the water solubility.
Adhesion of Chemical Vapor Deposited Boron Carbo-nitride to Dielectric and Copper Films
Authors: Engbrecht E.R. , Fitzpatrick P.R. , Junker K.H. , Sun Y-M. , White J.M. , Ekerdt J.G.
Published: August 2005

The interfacial adhesion energy was studied using the four-point bend method for boron carbo-nitride (BCxNy) deposited on dielectric and copper films. Twenty-five nanometer BCxNy films were deposited by chemical vapor deposition at 360 °C and 1 Torr using dimethylamine borane with no coreactant, NH3, or C2H4, producing different composition films, BC0.37N0.15, BC0.11N0.49, BC0.92N0.07, with dielectric constants of 4.1, 4.2, and 3.8, respectively. BCxNy films were deposited on dense and porous dielectrics, and copper. BCxNy films adhered strongly to the dielectric films and the composite beams snapped before debonding, revealing that the critical debond energy Gc exceeded 10 J/m2. The adhesion of BCxNy to oxidized copper increased with carbon content in the film, with the BC0.92N0.07 film beams snapping, and is possibly related to covalent bonding between surface oxygen and carbon in the film.
Cell Renewing in Neuroblastoma: Electrophysiological and Immunocytochemical Characterization of Stem Cells and Derivatives
Authors: Biagiotti Tiziana , D'Amico Massimo , Marzi Ilaria , Di Gennaro Paola , Arcangeli Annarosa , Wanke Enzo , Olivotto Massimo
Published: August 2005

We explored the stem cell compartment of the SH-SY5Y neuroblastoma (NB) clone and its development by a novel approach, integrating clonal and immunocytochemical investigations with patch-clamp measurements of ion currents simultaneously expressed on single cells. The currents selected were the triad IHERG, IKDR, INa, normally expressed at varying mutual ratios during development of neural crest stem cells, from which NB derives upon neoplastic transformation. These ratios could be used as electrophysiological clusters of differentiation (ECDs), identifying otherwise indistinguishable stages in maturation. Subcloning procedures allowed the isolation of highly clonogenic substrate-adherent (S-type) cells that proved to be p75- and nestinpositive and were characterized by a nude electrophysiological profile (ECDS0). These cells expressed negligible levels of the triad and manifested the capacity of generating the two following lineages: first, a terminally differentiating, smooth muscular lineage, positive for calponin and smooth muscle actin, whose electrophysiological profile is characterized by a progressive diminution of IHERG, the increase of IKDR and INa, and the acquisition of IKIR (ECDS2); second, a neuronal abortive pathway (NF-68 positive), characterized by a variable expression of IHERG and IKDR and a low expression of INa (ECDNS). This population manifested a vigorous amplification, monopolizing the stem cell compartment at the expense of the smooth muscular lineage to such an extent that neuronal-like (N-type) cells must be continuously removed if the latter are to develop.
Conversion of Human Umbilical Cord Mesenchymal Stem Cells in Wharton's Jelly to Dopaminergic Neurons In Vitro: Potential Therapeutic Application for Parkinsonism
Authors: Fu Yu-Show , Cheng Yun-Chih , Lin Maan-Yuh Anya , Cheng Henrich , Chu Pei-Ming , Chou Shih-Chich , Shih Yang-Hsin , Ko Miau-Hwa , Sung Min-Shan
Published: August 2005

Human mesenchymal stem cells isolated from Wharton's jelly of the umbilical cord were induced to transform into dopaminergic neurons in vitro through stepwise culturing in neuron-conditioned medium, sonic hedgehog, and FGF8. The success rate was 12.7%, as characterized by positive staining for tyrosine hydroxylase (TH), the rate-limiting catecholaminergic synthesizing enzyme, and dopamine being released into the culture medium. Transplantation of such cells into the striatum of rats previously made Parkinsonian by unilateral striatal lesioning with the dopaminergic neurotoxin 6-hydroxydopamine partially corrected the lesion-induced amphetamine-evoked rotation. Viability of the transplanted cells at least 4 months after transplantation was identified by positive TH staining and migration of 1.4 mm both rostrally and caudally. These results suggest that human umbilical mesenchymal stem cells have the potential for treatment of Parkinson's disease.