bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnosing comorbidity: concepts, criteria, and methods
Authors: Samet S. , Nunes E. V. , Hasin D. 
Published: February 2004

Background:The clinical and etiologic implications of comorbid psychiatric and substance-use disorders are relevant across countries and cultures. The DSM-IV now places greater emphasis on the clinical and research utility of the substance-induced disorders classification, and clarifies several important diagnostic issues specific to primary and substance-induced disorders. However, no research consensus exists over the core problem of identifying and differentiating the drug and alcohol intoxication and withdrawal symptoms that can mimic psychiatric symptoms in heavy drinkers and drug users.Objective:To investigate how various diagnostic instruments have measured comorbid psychiatric and substance-use disorders and how each instrument operationalizes the DSM-IV classification.Method:We review the evolution of the concept of comorbidity beginning with its formalization as the ‘primary–secondary’ distinction in the Feighner Criteria. We address the ‘organic–non-organic’ distinction found in the RDC, DSM-III, and DSM-III-R; and finally, review the ‘primary’ and ‘substance-induced’ categories of DSM-IV, DSM-IV-TR and ICD-10. We describe how these distinctions have been operationalized in widely used diagnostic instruments.Conclusion:Further understanding of these classifications and the relationship of co-occurring psychiatric and substance disorders can be accomplished with the range of available measures, particularly the Psychiatric Research Interview for Substance and Mental Disorders (PRISM), which reliably utilizes and refines DSM-IV classification distinctions.
Consistent Cytotoxic-T-Lymphocyte Targeting of Immunodominant Regions in Human Immunodeficiency Virus across Multiple Ethnicities
Authors: Frahm Nicole , Korber B. T. , Adams C. M. , Szinger J. J. , Draenert R. , Addo M. M. , Feeney M. E. , Yusim K. , Sango K. , Brown N. V. , SenGupta D. , Piechocka-Trocha A. , Simonis T. , Marincola F. M. , Wurcel A. G. , Stone D. R. , Russell C. J. , Adolf P. , Cohen D. , Roach T. , StJohn A. , Khatri A. , Davis K. , Mullins J. , Goulder P. J. R. , Walker B. D. , Brander C. 
Published: February 2004

ABSTRACTAlthough there is increasing evidence that virus-specific cytotoxic-T-lymphocyte (CTL) responses play an important role in the control of human immunodeficiency virus (HIV) replication in vivo, only scarce CTL data are available for the ethnic populations currently most affected by the epidemic. In this study, we examined the CD8+-T-cell responses in African-American, Caucasian, Hispanic, and Caribbean populations in which clade B virus dominates and analyzed the potential factors influencing immune recognition. Total HIV-specific CD8+-T-cell responses were determined by enzyme-linked immunospot assays in 150 HIV-infected individuals by using a clade B consensus sequence peptide set spanning all HIV proteins. A total of 88% of the 410 tested peptides were recognized, and Nef- and Gag-specific responses dominated the total response for each ethnicity in terms of both breadth and magnitude. Three dominantly targeted regions within these proteins that were recognized by >90% of individuals in each ethnicity were identified. Overall, the total breadth and magnitude of CD8+-T-cell responses correlated with individuals' CD4 counts but not with viral loads. The frequency of recognition for each peptide was highly correlated with the relative conservation of the peptide sequence, the presence of predicted immunoproteasomal cleavage sites within the C-terminal half of the peptide, and a reduced frequency of amino acids that impair binding of optimal epitopes to the restricting class I molecules. The present study thus identifies factors that contribute to the immunogenicity of these highly targeted and relatively conserved sequences in HIV that may represent promising vaccine candidates for ethnically heterogeneous populations.
THE EFFECT OF H ON THE ELECTRONIC STRUCTURE OF AN Fe(110)–Pd(100) INTERFACE
Authors: JASEN PAULA V. , GONZALEZ ESTELA A. , NAGEL OSCAR A. , JUAN ALFREDO 
Published: February 2004

The ion-driven mechanism in hydrogen permeation is substantially modified when iron is coated with palladium. A detailed knowledge of the electronic structure at the metal–metal interfaces is a prerequisite for understanding the process of H permeation. We have selected two low-Miller-index surfaces as a simple model for the interface. The system under consideration has 148 metallic atoms forming an Fe–Pd cluster distributed in six metallic layers. We have investigated the interaction of atomic hydrogen with the Fe (110)– Pd (100) interface using the semiempirical atom superposition and electron delocalization (ASED-MO) method. The changes in the electronic structures, density of states (DOS) and crystal overlap orbital population (COOP) in two different Fe–Pd interfaces were compared with the bulk ground states of both metals. The interfacial Fe–Pd distance results in about 1.74 Å, whereas for the Fe–Pd first neighbors distance it is about 1.85 Å. An important conclusion is that the metal–metal bonds at the interface are stronger than those bonds in the pure metal bulk. A favorable metal adhesion is observed, as revealed by the energetic stabilization of the composite metal system. H is stabilized near the FePd interface and stopped at the first Pd layer. A H–metal bond is developed with both Fe and Pd atoms while Fe–Pd bonding at the interface remains unaltered.
Field Physiology: Physiological Insights from Animals in Nature
Authors: Costa Daniel P. , Sinervo Barry 
Published: February 2004

▪ Abstract  Whereas comparative physiology documents the range of physiological variation across a range of organisms, field physiology provides insight into the actual mechanisms an organism employs to maintain homeostasis in its everyday life. This requires an understanding of an organism's natural history and is prerequisite to developing hypotheses about physiological mechanisms. This review focuses on a few areas of field physiology that exemplify how the underlying physiology could not have been understood without appropriate field measurements. The examples we have chosen highlight the methods and inference afforded by an application of this physiological analysis to organismal function in nature, often in extreme environments. The specific areas examined are diving physiology, the thermal physiology of large endothermic fishes, reproductive physiology of air breathing vertebrates, and endocrine physiology of reproductive homeostasis. These areas form a bridge from physiological ecology to evolutionary ecology. All our examples revolve around the central issue of physiological limits as they apply to organismal homeostasis. We view this theme as the cornerstone of physiological analysis and supply a number of paradigms on homeostasis that have been tested in the context of field physiology.
The Cytochrome bc1 Complex: Function in the Context of Structure
Authors: Crofts Antony R. 
Published: February 2004

▪ Abstract  The bc 1 complexes are intrinsic membrane proteins that catalyze the oxidation of ubihydroquinone and the reduction of cytochrome c in mitochondrial respiratory chains and bacterial photosynthetic and respiratory chains. The bc 1 complex operates through a Q-cycle mechanism that couples electron transfer to generation of the proton gradient that drives ATP synthesis. Genetic defects leading to mutations in proteins of the respiratory chain, including the subunits of the bc 1 complex, result in mitochondrial myopathies, many of which are a direct result of dysfunction at catalytic sites. Some myopathies, especially those in the cytochrome b subunit, exacerbate free-radical damage by enhancing superoxide production at the ubihydroquinone oxidation site. This bypass reaction appears to be an unavoidable feature of the reaction mechanism. Cellular aging is largely attributable to damage to DNA and proteins from the reactive oxygen species arising from superoxide and is a major contributing factor in many diseases of old age. An understanding of the mechanism of the bc 1 complex is therefore central to our understanding of the aging process. In addition, a wide range of inhibitors that mimic the quinone substrates are finding important applications in clinical therapy and agronomy. Recent structural studies have shown how many of these inhibitors bind, and have provided important clues to the mechanism of action and the basis of resistance through mutation. This paper reviews recent advances in our understanding of the mechanism of the bc 1 complex and their relation to these physiologically important issues in the context of the structural information available.
Thrombin activatable fibrinolysis inhibitor (TAFI) and markers of endothelial cell injury in dialyzed patients with diabetic nephropathy
Authors: Małyszko Jacek , Hryszko Tomasz , Myśliwiec Michał , Małyszko Jolanta 
Published: February 2004

SummaryPatients dialyzed due to diabetic nephropathy are at a higher risk of death due to cardiovascular complications than dialyzed non-diabetic patients. Disturbances in hemostasis may play a role in the vascular complications of diabetes mellitus. It has been postulated that TAFI-thrombin activatable fibrinolysis inhibitor, which couples two opposite systems: coagulation and fibrinolysis, may be involved in the mechanism of vascular endothelial damage in diabetic patients. We assessed: TAFI and TAFIa, markers of ongoing coagulation: thrombin-antithrombin complexes, prothrombin fragments 1+2, a marker of ongoing fibrinolysis: plasmin-antiplasmin complexes in diabetic and non-diabetic patients on hemodialyses-HD, peritoneal dialysesCAPD, patietns with chronic renal failure with and without diabetic nephropathy on conservative treatment. Both groups of dialyzed diabetic patients have a higher concentration of markers of ongoing coagulation and TAFI activity when compared to dialyzed non-diabetic patients. Linear regression analysis showed that TAFI concentration was directly related to albumin in HD and CAPD patients without diabetic nephropathy, whereas TAFIa correlated with triglycerides, fibrinogen and leukocytes count in this group. When evaluated separately (HD, CAPD), significant correlations between TAFIa and triglycerides and fibrinogen were found only in diabetic CAPD patients. Multivariate analysis showed no correlation between TAFI and other parameters studied. In conclusion, elevated circulating TAFI and TAFIa might be a new link in the pathogenesis of impaired fibrinolysis in diabetic nephropathy, and thus atherosclerosis progression, particularly in CAPD patients. Hypercoagulable state observed in diabetic patients on conservative treatment and maintained on dialyses may contribute to the higher cardiovascular mortality in this population. In these patients there is also evidence of endothelial injury, and probably secondary activation of the coagulation cascade.
Autologous transplantation of peripheral blood stem cells as an effective therapeutic approach for severe arteriosclerosis obliterans of lower extremities
Authors: Huang Ping , Li Shan , Han Ming , Xiao Zhi , Yang Ren , Qiu Lu , Han Zhong 
Published: February 2004

SummaryTreatment of severe arteriosclerosis obliterans of lower extremities (ASOLE) remains a clinical challenge. To develop a more effective approach, we evaluated the clinical efficacy of autologous transplantation of mobilized peripheral blood stem cells (PBSCs) in 5 patients with ASOLE. The patients received recombinant human granulocyte colony-stimulating factor (rhG-CSF, 600 μg/day) for 5 consecutive days. On day 5, PBSCs were collected, sorted from blood circulation of patients, and then intramuscularly injected into their ischemic lower limbs. A significant improvement of clinical manifestations including severe pain, skin temperature and ulcer, was observed, without obvious adverse effect. The patient’s limb was successfully saved. Satisfactory remission was obtained 3 months after transplantation as shown by significant improvement in anklebrachial pressure index (ABI), blood flow in personal vascular laboratory (PVL), laser Doppler blood perfusion, and the angiographic scores. Our data suggest for the first time that autologous transplantation of mobilized PBSCs provides a practical, safe, and effective method of treatment for lower limb ischemia.
Expression of tissue factor pathway inhibitor-2 in murine and human liver regulation during inflammation
Authors: Hisaka Toru , Lardeux Bernard , Lamireau Thierry , Wüestefeld Torsten , Lalor Patricia , Neaud Véronique , Maurel Patrick , Desmoulière Alexis , Kisiel Walter , Trautwein Christian , Rosenbaum Jean 
Published: February 2004

SummaryTissue factor pathway inhibitor-2 (TFPI-2) is a recently described serine proteinase inhibitor. Human and murine TFPI-2 share about 50% homology. The aim of this study was to investigate the cellular localization of human and murine TFPI-2 in the liver and the regulation of their expression during acute inflammation. Northern blot, in situ hybridization and studies on isolated hepatocytes demonstrated a high-level expression of TFPI-2 in murine hepatocytes. On the other hand, very little TFPI-2 mRNA expression could be detected in human liver. Studies with isolated human liver cells suggested that TFPI-2 expression in human liver was mainly observed in liver sinusoidal endothelial cells rather than hepatocytes. Liver murine TFPI-2 expression was greatly increased after lipopolysaccharide administration with a delayed kinetics as compared to α1-acid glycoprotein, a classical acute-phase reactant. Accordingly, studies with isolated cells showed that the increase in TFPI-2 transcripts occurred in non-hepatocytic cells. Moreover, the LPS response was abolished in mice with a hepatocyte-specific KO for the gp130 receptor, thus indicating that a mediator from hepatocytes is involved in the up-regulation of TFPI-2 in non-parenchymal cells. In conclusion, murine TFPI-2 is highly expressed in hepatocytes in the normal murine liver and is upregulated in non-parenchymal cells in the context of inflammation. The large difference in the level of liver expression of human and murine TFPI-2 suggests that despite significant sequence similarities, these proteins presumably have different functions in the two species.
Platelet kinetics and scintigraphic imaging in thrombocytopenic malaria patients
Authors: Zedwitz-Liebenstein Konstantin , Eidherr Harald , Schuetz Matthias , Sauerman Robert , Dudczak Robert , Winkler Stefan , Pabinger Ingrid , Kletter Kurt , Karanikas Georgios 
Published: February 2004

SummaryThrombocytopenia is a common occurrence in acute malaria. It is attributed, among other factors, to excessive splenic platelet pooling and a shortened platelet lifespan. The aim of our study was to evaluate the platelet kinetics and sequestration site by isotopic studies in uncomplicated malaria-induced thrombocytopenia. Seven thrombocytopenic malaria patients (74,000±36,000 platelets/µl) were included in the study. Autologous 111In-labeled platelet scintigraphy was performed up to 96 hours (h) post injection (p.i.) to evaluate the platelet sequestration site. Late sequestration for the spleen (S) and the liver (L) was analyzed according to the following activity ratios: S (spleen count on the last day of the platelet lifespan / spleen count at 30 min) and L (liver count on the last day of the platelet lifespan / liver count at 30 min). Additionally, platelet survival studies were performed. A normal late sequestration (S: 0.95±0.06 and L: 1.04±0.08; normal values, S and L: 1 ± 0.2.) was observed in all of our patients. The platelet lifespan was reduced (1 to 4 days; normal range, 7-9 days), recovery was normal (mean, 63±6%; normal range, 55-75%), and the turnover rate was enhanced (mean, 95,000±80,000/µl/day; normal value, 35,000±4,500/µl/ day). According to the results of scintigraphy, the sequestration site by uncomplicated malaria-induced thrombocytopenia appears to be non-splenic and/or hepatic, yet diffuse.
Serum albumin predicts cardiac adverse events in patients with advanced atherosclerosis – interrelation with traditional cardiovascular risk factors
Authors: Exner Markus , Mlekusch Wolfgang , Amighi Jasmin , Sabeti Schila , Schlager Oliver , Wagner Oswald , Minar Erich , Schillinger Martin 
Published: February 2004

SummaryLow serum albumin is a powerful predictor of cardiovascular adverse events in healthy subjects and patients with subclinical atherosclerosis. We investigated the association between serum albumin, traditional cardiovascular risk factors, markers of inflammation and cardiovascular outcome in 515 patients with advanced atherosclerosis and severe peripheral artery disease. Cardiovascular risk profile, serum albumin, serum amyloid A (SAA) and fibrinogen were obtained at baseline, and patients were followed for median 21 months (interquartile range 12 to 25) for the occurrence of major adverse cardiac events (MACE: myocardial infarction, percutaneous coronary interventions, coronary artery bypass graft, and death). We observed 135 MACE in 109 patients (21%). Cumulative event-free survival rates at 6, 12, and 24 months were 95%, 91%, and 80%, respectively. Low albumin predicted MACE independently of SAA and fibrinogen. Adjusted hazard ratios for the occurrence of MACE, any death, and the composite of death and MI according to increasing quartiles of albumin were 2.40, 1.14 and 1.09 (p<0.001), 2.94, 1.34 and 1.11 (p=0.003) and 3.63, 1.86 and 1.29 (p<0.001), respectively, as compared to the highest quartile. Considering albumin in conjunction with traditional cardiovascular risk factors (smoking, hyperlipidemia, hypertension and diabetes), we found that low albumin predicted MACE only in patients with a low risk profile (less than 3 risk factors) (p<0.001), whereas low albumin was not associated with MACE in patients with three or more risk factors (p=0.66). We conclude that low serum albumin is associated with cardiovascular outcome of patients with advanced atherosclerosis adding to the prognostic information of other inflammatory markers, and may be particularly useful for risk prediction in patients with few traditional risk factors.
Impaired brain angiogenesis and neuronal apoptosis induced by conditional homozygous inactivation of vascular endothelial growth factor
Authors: Raab Sabine , Beck Heike , Gaumann Andreas , Yüce Ali , Gerber Hans-Peter , Plate Karl , Hammes Hans-Peter , Ferrara Napoleone , Breier Georg 
Published: February 2004

SummaryVascular endothelial growth factor (VEGF) is essential for the differentiation of the primitive embryonic vascular system and has been implicated in the vascularization of organs. Recently, VEGF has also been proposed to play a role in neural development, neuroprotection, and adult neurogenesis. Here we have investigated the function of VEGF in the developing brain by cre-lox technology. We show that VEGF produced by the embryonic neuroectoderm is required for the vascularization and the development of the brain. Both the invasion and the directed growth of capillaries were severely impaired in the fore-, midand hindbrain of VEGFlox/lox/nestin-cre mouse embryos homozygous for a VEGF mutation in the neural tube. These observations demonstrate thatVEGF, via local secretion by neural progenitors, induces brain angiogenesis and guides the growth of capillaries toward the ventricular zone. VEGF deficiency led to developmental retardation and progressive destruction of neural tissue in all brain regions.The defect was most pronounced in telencephalic structures, such as the hippocampus, and caused microcephaly.Taken together, the findings establish the critical importance of neuroectoderm-derived VEGF in the morphogenesis of the brain. VEGF acts as a key regulator of brain angiogenesis and provides instructive cues for the correct spatial organization of the vasculature.
Age- and sex-specific incidence, risk, and latency period of a perioperative acute thromboembolism syndrome (PATS)
Authors: Takada Tomosue , Sato Shigehito , Kikura Mutsuhito 
Published: February 2004

SummaryWe investigated age- and sex-specific incidence, risk factors, and latency period of a perioperative acute thromboembolism syndrome (PATS) in a large cohort study. We prospectively analyzed data on 21903 consecutive surgery patients to determine the incidence of myocardial infarction, pulmonary embolism, deep venous thrombosis, stroke, and cardiovascular death within 30 postoperative days. Among 255 (1.2 percent) patients with thromboembolism, 105 (0.48 percent) suffered myocardial infarction (mean latency: 5 days), 30 (0.14 percent) suffered pulmonary embolism (6 days), 23 (0.11 percent) suffered deep venous thrombosis (10 days), 97 (0.44 percent) suffered stroke (11 days), and 13 (0.06 percent) died (12 days). The critical period was postoperative week 1 for myocardial infarction and pulmonary embolism, and postoperative week 1 and 2 for deep venous thrombosis, stroke, and death. Risk of all events increased with age (P<0.0001), particularly for over 70 years (odds ratio: 12.5; 95 percent confidence interval, 7.8 to 19.9). Males had an increased risk (P<0.0001) of myocardial infarction (odds ratio; 1.5; 95 percent confidence interval, 1.0 to 2.3). Females had an increased risk (P<0.0001) of pulmonary embolism (odds ratio: 2.7; 95 percent confidence interval, 1.3 to 5.9) and deep venous thrombosis (odds ratio: 9.8; 95 percent confidence interval, 3.3 to 29.3). Risk of thromboembolic event was higher (P<0.0001) in patients with a history of arterial thrombotic events or cancer. Trend analysis indicates that thromboembolic events will increase 3-fold over the next decade. Our findings enable identification of higher risk patients for prophylactic anti-thromboembolic treatment and awareness of the critical postoperative period.
Treatment with anticoagulants in cerebral events (TRACE)
Authors: Woessner Ralph , Grauer Markus , Bianchi Oliver , Mueller Martin , Moersdorf Stefan , Berlit Peter , Goertler Michael , Grotemeyer Karl-Heinz , Sliwka Ulrich , Stoll Martin , Treib Johannes 
Published: February 2004

Summary90 patients with acute stroke and a concomitant cardiac embolism source or a symptomatic high-grade stenosis of an extraor intracranial vessel received in a mulitcenter, randomized, controlled study either Enoxaparin 1 mg/kg BW s.c. b.i.d. or i.v. heparin aPTT-adjusted daily for 8 +/−2 days as secondary prophylaxis. There were no significant differences between the two groups regarding cerebral and systemic embolic events, bleeding complications, length of hospital stay, number of diagnostic and therapeutic measures and outcome after three months. This suggests that Enoxaparin, which is easier to administer and monitor, is a safe drug in patients with acute cerebral events.
The structural basis for the pathophysiological relevance of PAI-1 in cardiovascular diseases and the development of potential PAI-1 inhibitors
Authors: Gils Ann , Declerck Paul 
Published: February 2004

SummaryPlasminogen activator inhibitor-1 (PAI-1) is an important component of the plasminogen/plasmin system as it is the main inhibitor of tissue-type and urokinase-type plasminogen activator. Consequently, PAI-1 plays an important role in cardiovascular diseases (mainly through inhibition of t-PA), and in cell migration and tumor development (mainly through inhibition of u-PA and interaction with vitronectin). As a member of the serpin superfamily, PAI-1 shares important structural properties with other serpins. However, PAI-1 also exhibits unique conformational and functional properties. The current review provides an overview of the knowledge on PAI-1 gathered since its discovery two decades ago. We discuss (a) its structural properties of the protein and their subsequent relation to functional activities, (b) its role in a wide variety of (patho) physiological processes and (c) a number of strategies to interfere with its functional properties eventually aiming at pharmacological modulation of this risk factor.