bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vascular disease risk factors as determinants of incident depressive symptoms: a prospective community-based study
Authors: CERVILLA J. , PRINCE M. , RABE-HESKETH S. 
Published: May 2005

Background. The potential association between vascular disease and depression have been the focus for much clinical psychiatric research, although few epidemiological prospective studies have looked into this association.Aims. This study explores the a priori hypothesis of a prospective association between cardiovascular disease or its risk factors and incident depressive symptoms.Method. A prospective primary care based study derived from a multi-centre randomized controlled trial of moderate hypertension. 2584 moderately-hypertensive volunteers were followed-up for 54 months when five assessments of depressive symptoms, vascular disease and its risk factors were made.Results. We found an association between the dependent variable (incident depressive symptoms measured with the Self-CARE-D) and baseline smoker status, low serum cholesterol levels, poorer cognitive function (particularly executive dysfunction), female gender and increasing age. These associations were independent of all other cardiovascular risk factors (ECG evidence of ischaemia or arrythmia, systolic or diastolic blood pressure, blood pressure decline along the trial and body mass index).Conclusions. Our results do not support the hypothesis of a specific association between vascular disease or its risk factors and incident depressive symptoms.
Relationship of behavioural and symptomatic syndromes in schizophrenia to spatial working memory and attentional set-shifting ability
Authors: PANTELIS C. , HARVEY C. A. , PLANT G. , FOSSEY E. , MARUFF P. , STUART G. W. , BREWER W. J. , NELSON H. E. , ROBBINS T. W. , BARNES T. R. E. 
Published: May 2005

Background. Behavioural syndromes (thought disturbance, social withdrawal, depressed behaviour and antisocial behaviour) offer a different perspective from that of symptomatic syndromes on the disability that may be associated with schizophrenia. Few studies have assessed their relationship with neuropsychological deficits. We hypothesized that these syndromes may represent behavioural manifestations of frontal-subcortical impairments, previously described in schizophrenia.Method. Long-stay inpatients (n=54) and community patients (n=43) with enduring schizophrenia were assessed, using measures of symptoms and behaviour and tests of executive functioning. The relationship between syndromes and neuropsychological function was assessed using multiple regression and logistic regression analyses.Results. Significant associations were found between performance on the spatial working memory task and the psychomotor poverty symptomatic syndrome, and between attentional set-shifting ability and both disorganization symptoms and the thought disturbance behavioural syndrome. These results were not explained by the effect of premorbid IQ, geographical location, length of illness or antipsychotic medication. Length of illness was an independent predictor of attentional set-shifting ability but not of working memory performance.Conclusion. The specific relationship between negative symptoms and spatial working memory is consistent with involvement of the dorsolateral prefrontal cortex. The associations between difficulty with set-shifting ability and both disorganization symptoms and behaviours may reflect inability to generalize a rule that had been learned and impaired ability to respond flexibly. The specific relationship of illness duration to set-shifting ability may suggest progressive impairment on some executive tasks. The nature of these relationships and their neurobiological and rehabilitation implications are considered.
Major depression in community-dwelling middle-aged and older adults: prevalence and 2- and 4-year follow-up symptoms
Authors: MOJTABAI RAMIN , OLFSON MARK 
Published: May 2005

Background. Although major depression is a common condition across the age range, there is some evidence from clinical studies that it may be more persistent and disabling in older adults. This study examined the demographic, socio-economic and clinical factors associated with major depression and with persistence of depressive symptoms at 2- and 4-year follow-ups in a large population sample of middle-aged and older adults.Method. In a sample of 9747 participants aged over 50 in the 1996 wave of the US Health and Retirement Study, the authors assessed the 12-month prevalence of major depression using the Composite International Diagnostic Interview – Short Form (CIDI-SF). Significant depressive symptoms at the time of 1996, 1998 and 2000 interviews were assessed using a short form of the Center for Epidemiological Studies Depression Scale (CES-D).Results. The 12-month prevalence of CIDI-SF major depression was 6·6%. With age, prevalence declined, but the likelihood of significant depressive symptoms at follow-ups increased. Both prevalence and persistence of significant depressive symptoms at follow-ups were associated with socio-economic disadvantage and physical illness. Persistence of depressive symptoms at follow-ups was also associated with symptoms of anhedonia, feelings of worthlessness, and thoughts of death at baseline.Conclusions. Sociodemographic, physical health and a specific profile of depressive symptoms are associated with a poorer course of major depression in the middle-aged and older adults. These indicators may identify a subgroup of patients in need of more careful follow-up and intensive treatment.
The relation between suicidal feelings and mental disorders in the elderly: results from the Berlin Aging Study (BASE)
Authors: BARNOW S. , LINDEN M. , FREYBERGER H.-J. 
Published: May 2005

Background. The purpose of this study was to demonstrate the influence of several risk factors (particularly physical and mental disorders, loneliness and housing conditions) on the wish to die in the elderly.Method. Using data from a population-based sample of 516 senior citizens (70 to 103 years of age) in Berlin (Germany), we compared 54 persons with death wishes with 462 persons without death wishes on several psychosocial risk factors, physical health and psychiatric diagnoses. A logistic regression analysis was also conducted.Results. The data indicate that the wish to die is strongly associated with the presence of a mental disorder, especially major depression, while higher age, female gender, subjective assessment of physical health and negative living conditions were all only moderately related to death wishes.Conclusions. Our results emphasize the need for very careful diagnosis of death wishes in the very old and question the view that it is a normal and understandable phenomenon in older age.
Functional magnetic resonance imaging of the cerebral response to visual stimulation in medically unexplained visual loss
Authors: WERRING D. J. , WESTON L. , BULLMORE E. T. , PLANT G. T. , RON M. A. 
Published: May 2005

Background. Medically unexplained visual loss occurs in 1 to 5% of patients attending ophthalmology clinics and for many it runs a chronic course. A psychogenic aetiology is presumed in such cases, but little is known about the underlying neural mechanisms. Recent studies have established the value of functional magnetic resonance imaging (fMRI) in understanding the mechanisms of unexplained motor and sensory symptoms. The purpose of this study was to use a similar strategy (fMRI) to evaluate the cerebral responses to visual stimulation in a group of patients with medically unexplained visual loss, in an attempt to determine the underlying neural mechanisms.Method. Brain activation induced by periodic (monocular) 8 Hz visual stimulation was detected by fMRI in five patients with unexplained visual loss who fulfilled DSM-IV criteria for conversion disorder, and seven normal volunteers. Between-group differences in mean power of activation were estimated by fitting a one-way analysis of variance (ANOVA) model at each intracerebral voxel in standard space.Results. Compared with controls, patients showed reduced activation in visual cortices, but increased activation in left inferior frontal cortex, left insula-claustrum, bilateral striatum and thalami, left limbic structures, and left posterior cingulate cortex.Conclusions. This preliminary study has identified novel neural correlates in patients with unexplained visual loss. The abnormal pattern of activation may reflect inhibition of primary visual cortex or a shift towards non-conscious (implicit) processing.
Persecutory delusions and the determination of self-relevance: an fMRI investigation
Authors: BLACKWOOD N. J. , BENTALL R. P. , FFYTCHE D. H. , SIMMONS A. , MURRAY R. M. , HOWARD R. J. 
Published: May 2005

Background. People with persecutory delusions regard ambiguous data in the social domain as self-relevant and selectively attend to threatening information. This study aimed to characterize these social cognitive biases in functional neuroanatomical terms.Method. Eight schizophrenic patients with active persecutory delusions and eight matched normal controls underwent functional magnetic resonance imaging while determining the self-relevance of ambiguous self-relevant or unambiguous other-relevant neutral and threatening statements.Results. In determining self-relevance, the deluded subjects showed a marked absence of rostral–ventral anterior cingulate activation together with increased posterior cingulate gyrus activation in comparison to the normal subjects. The influence of threat on self-relevance determination did not yield statistically significant differences between deluded and normal subjects.Conclusions. Abnormalities of cingulate gyrus activation while determining self-relevance suggest impaired self-reflection in the persecutory deluded state. This may contribute to persecutory belief formation and maintenance.
On the evaluation of ‘saving-consumption’ plans
Authors: VANDUFFEL STEVEN , DHAENE JAN , GOOVAERTS MARC 
Published: May 2005

Knowledge of the distribution function of the stochastically compounded value of a series of future (positive and/or negative) payments is needed for solving several problems in an insurance or finance environment, see e.g. Dhaene et al. (2002a,b). In Kaas et al. (2000), convex lower-bound approximations for such a sum have been proposed. In case of changing signs of the payments however, the distribution function or the quantiles of the lower bound are not easy to determine, as the approximation for the random compounded value of the payments will in general not be a comonotonic sum.In this paper, we present a method for determining accurate and easy computable approximations for risk measures of such a sum, in case one first has positive payments (savings), followed by negative ones (consumptions).This particular cashflow pattern is observed in ‘saving–consumption’ plans. In such plans, a person saves money on a regular basis for a certain number of years. The amount available at the end of this period is then used to generate a yearly pension for a fixed number of years. Using the results of this paper we can find accurate and easy to compute answers to questions such as: ‘What is the minimal required yearly savings effort, α, during a fixed number of years, such that we will be able to meet, with a probability of at least (1−ε), a given consumption pattern during the withdrawal period?’
Community outreach to patients with AIDS at the end of life in the
inner city: Reflections from the trenches
Authors: LA FOSSE HECTOR , SCHWARTZ CHARLES E. , CARABALLO ROSA J. , GOEREN WILLIAM , SELWYN PETER A. 
Published: May 2005

Indigenous community health outreach workers (CHWs), who serve as a
bridge between underserved, difficult-to-reach minority populations and
health professionals, can play a critical role in bringing palliative care
to patients dying of AIDS and other illnesses in the inner city. Although
the contribution of CHWs in the delivery of “curative” and
preventive services has been well established, little attention has been
given to CHWs in palliative care.Integrating the medical literature with experiences of a team
providing HIV palliative care in the Bronx, a descriptive typology of
critical stages and components in the work of CHWs in end-of-life care in
the inner city is presented. A longitudinal case narrative, told from the
perspective of the CHW, is used to demonstrate the richness and complexity
of the CHW's role.The article concludes with a description of the experience of the CHW,
straddling two worlds—the world of the inner city patient and the
world of the health care providers—and explores the special
characteristics of the individuals who can fill this vital role in
palliative care.
Brain cancer and sexual health: A case report
Authors: KRYCHMAN MICHAEL L. , AMSTERDAM ALISON , CARTER JEANNE , CASTIEL MERCEDES , DeANGELIS LISA 
Published: May 2005

Objective: Cancer patients often encounter sexual concerns
during the diagnosing, treatment, and recovery phase of their illness.
However, the sexual concerns of these patients are often overlooked. Brain
cancer patients are no exception to this oversight.Methods: A case report of a 39-year-old patient with a
history of high-grade anaplastic astrocytoma presented to the Sexual
Health Program at the Memorial Sloan-Kettering Cancer Center complaining
of vaginal discharge and several months of amenorrhea. Although the
patient was administered extensive aggressive antineoplastic treatments,
her disease rapidly progressed.Results: Despite the patient's terminal illness she
continued to have normal sexual thoughts, feelings, and desires; however,
she had difficulty discussing these issues with her partner and caregiver,
who was her mother. An examination by the sexual medicine gynecologist
noted no clinical signs of genital infections; however, there was minimal
vaginal atrophy. Her sexual health laboratory evaluation was extensively
abnormal. Her treatment consisted of intravaginal non-hormonal
moisturizers and vaginal lubricants, counseling, and sexual education. The
patient successfully engaged in sexual contact with her partner by the
third counseling session.Significance of Results: Almost all oncology patients have
sexual concerns during or following cancer treatment. These patients
should be referred to comprehensive sexual health programs for treatment,
if available.
Molecular, functional and structural properties of the prolyl oligopeptidase ofTrypanosoma cruzi(POP Tc80), which is required for parasite entry into mammalian cells
Authors: BASTOS Izabela M. D. , GRELLIER Philippe , MARTINS Natalia F. , CADAVID-RESTREPO Gloria , de SOUZA-AULT Marian R. , AUGUSTYNS Koen , TEIXEIRA Antonio R. L. , SCHRÉVEL Joseph , MAIGRET Bernard , da SILVEIRA José F. , SANTANA Jaime M. 
Published: May 2005

We have demonstrated that the 80 kDa POP Tc80 (prolyl oligopeptidase of Trypanosoma cruzi) is involved in the process of cell invasion, since specific inhibitors block parasite entry into non-phagocytic mammalian host cells. In contrast with other POPs, POP Tc80 is capable of hydrolysing large substrates, such as fibronectin and native collagen. In this study, we present the cloning of the POPTc80 gene, whose deduced amino acid sequence shares considerable identity with other members of the POP family, mainly within its C-terminal portion that forms the catalytic domain. Southern-blot analysis indicated that POPTc80 is present as a single copy in the genome of the parasite. These results are consistent with mapping of POPTc80 to a single chromosome. The active recombinant protein (rPOP Tc80) displayed kinetic properties comparable with those of the native enzyme. Novel inhibitors were assayed with rPOP Tc80, and the most efficient ones presented values of inhibition coefficient Ki≤1.52 nM. Infective parasites treated with these specific POP Tc80 inhibitors attached to the surface of mammalian host cells, but were incapable of infecting them. Structural modelling of POP Tc80, based on the crystallized porcine POP, suggested that POP Tc80 is composed of an α/β-hydrolase domain containing the catalytic triad Ser548–Asp631–His667 and a seven-bladed β-propeller non-catalytic domain. Docking analysis suggests that triple-helical collagen access to the catalytic site of POP Tc80 occurs in the vicinity of the interface between the two domains.
Identification and characterization of a second 4,4′-dibenzamido-2,2′-stilbenedisulphonate (DBDS)-binding site on band 3 and its relationship with the anion/proton co-transport function
Authors: SALHANY James M. , CORDES Karen S. , SLOAN Renee L. 
Published: May 2005

Band 3 mediates both electroneutral AE (anion exchange) and APCT (anion/proton co-transport). Protons activate APCT and inhibit AE with the same pK (∼5.0). SDs (stilbenedisulphonates) bind to a primary, high-affinity site on band 3 and inhibit both AE and APCT functions. In this study, we present fluorescence and kinetic evidence showing that lowering the pH activates a second site on band 3, which binds DBDS (4,4′-dibenzamido-2,2′-stilbenedisulphonate) independently of chloride concentration, and that DBDS binding to the second site inhibits the APCT function of band 3. Activation of the second site correlated with loss of chloride binding to the transport site, thus explaining the lack of competition. The kinetics of DBDS binding at the second site could be simulated by a slow-transition, two-state exclusive binding mechanism (R0↔T0+D↔TD↔RD, where D represents DBDS, R0 and T0 represent alternate conformational states at the second DBDS-binding site, and TD and RD are the same two states with ligand DBDS bound), with a calculated overall Kd of 3.9 μM and a T0+D↔TD dissociation constant of 55 nM. DBDS binding to the primary SD site inhibited approx. 94% of the proton transport at low pH (KI=68.5±11.8 nM). DBDS binding to the second site inhibited approx. 68% of the proton transport (KI=7.27±1.27 μM) in a band 3 construct with all primary SD sites blocked through selective cross-linking by bis(sulphosuccinimidyl)suberate. DBDS inhibition of proton transport at the second site could be simulated quantitatively within the context of the slow-transition, two-state exclusive binding mechanism. We conclude that band 3 contains two DBDS-binding sites that can be occupied simultaneously at low pH. The binding kinetic and transport inhibition characteristics of DBDS interaction with the second site suggest that it may be located within a gated access channel leading to the transport site.
The transcriptional co-activator TAZ interacts differentially with transcriptional enhancer factor-1 (TEF-1) family members
Authors: MAHONEY William M. , HONG Jeong-Ho , YAFFE Michael B. , FARRANCE Iain K. G. 
Published: May 2005

Members of the highly related TEF-1 (transcriptional enhancer factor-1) family (also known as TEAD, for TEF-1, TEC1, ABAA domain) bind to MCAT (muscle C, A and T sites) and A/T-rich sites in promoters active in cardiac, skeletal and smooth muscle, placenta, and neural crest. TEF-1 activity is regulated by interactions with transcriptional co-factors [p160, TONDU (Vgl-1, Vestigial-like protein-1), Vgl-2 and YAP65 (Yes-associated protein 65 kDa)]. The strong transcriptional co-activator YAP65 interacts with all TEF-1 family members, and, since YAP65 is related to TAZ (transcriptional co-activator with PDZ-binding motif), we wanted to determine if TAZ also interacts with members of the TEF-1 family. In the present study, we show by GST (glutathione S-transferase) pull-down assays, by co-immunoprecipitation and by modified mammalian two-hybrid assays that TEF-1 interacts with TAZ in vitro and in vivo. Electrophoretic mobility-shift assays with purified TEF-1 and GST–TAZ fusion protein showed that TAZ interacts with TEF-1 bound to MCAT DNA. TAZ can interact with endogenous TEF-1 proteins, since exogenous TAZ activated MCAT-dependent reporter promoters. Like YAP65, TAZ interacted with all four TEF-1 family members. GST pull-down assays with increasing amounts of [35S]TEF-1 and [35S]RTEF-1 (related TEF-1) showed that TAZ interacts more efficiently with TEF-1 than with RTEF-1. This differential interaction also extended to the interaction of TEF-1 and RTEF-1 with TAZ in vivo, as assayed by a modified mammalian two-hybrid experiment. These data show that differential association of TEF-1 proteins with transcriptional co-activators may regulate the activity of TEF-1 family members.
A mammalian fatty acid hydroxylase responsible for the formation of α-hydroxylated galactosylceramide in myelin
Authors: ECKHARDT Matthias , YAGHOOTFAM Afshin , FEWOU Simon N. , ZÖLLER Inge , GIESELMANN Volkmar 
Published: May 2005

Hydroxylation is an abundant modification of the ceramides in brain, skin, intestinal tract and kidney. Hydroxylation occurs at the sphingosine base at C-4 or within the amide-linked fatty acid. In myelin, hydroxylation of ceramide is exclusively found at the α-C atom of the fatty acid moiety. α-Hydroxylated cerebrosides are the most abundant lipids in the myelin sheath. The functional role of this modification, however, is not known. On the basis of sequence similarity to a yeast C26 fatty acid hydroxylase, we have identified a murine cDNA encoding FA2H (fatty acid 2-hydroxylase). Transfection of FA2H cDNA in CHO cells (Chinese-hamster ovary cells) led to the formation of α-hydroxylated fatty acid containing hexosylceramide. An EGFP (enhanced green fluorescent protein)–FA2H fusion protein co-localized with calnexin, indicating that the enzyme resides in the endoplasmic reticulum. FA2H is expressed in brain, stomach, skin, kidney and testis, i.e. in tissues known to synthesize fatty acid α-hydroxylated sphingolipids. The time course of its expression in brain closely follows the expression of myelin-specific genes, reaching a maximum at 2–3 weeks of age. This is in agreement with the reported time course of fatty acid α-hydroxylase activity in the developing brain. In situ hybridization of brain sections showed expression of FA2H in the white matter. Our results thus strongly suggest that FA2H is the enzyme responsible for the formation of α-hydroxylated ceramide in oligodendrocytes of the mammalian brain. Its further characterization will provide insight into the functional role of α-hydroxylation modification in myelin, skin and other organs.
Plasmin alters the activity and quaternary structure of human plasma carboxypeptidase N
Authors: QUAGRAINE Mercy O. , TAN Fulong , TAMEI Hironori , ERDÖS Ervin G. , SKIDGEL Randal A. 
Published: May 2005

Human CPN (carboxypeptidase N) is a tetrameric plasma enzyme containing two glycosylated 83 kDa non-catalytic/regulatory subunits that carry and protect two active catalytic subunits. Because CPN can regulate the level of plasminogen binding to cell surface proteins, we investigated how plasmin cleaves CPN and the consequences. The products of hydrolysis were analysed by activity assays, Western blotting, gel filtration and sequencing. When incubated with intact CPN tetramer, plasmin rapidly cleaved the 83 kDa subunit at the Arg457–Ser458 bond near the C-terminus to produce fragments of 72 and 13 kDa, thereby releasing an active 142 kDa heterodimer, and also cleaved the active subunit, decreasing its size from 55 kDa to 48 kDa. Further evidence for the heterodimeric form of CPN was obtained by re-complexing the non-catalytic 72 kDa fragment with recombinant catalytic subunit or by immunoprecipitation of the catalytic subunit after plasmin treatment of CPN using an antibody specific for the 83 kDa subunit. Upon longer incubation, plasmin cleaved the catalytic subunit at Arg218–Arg219 to generate fragments of 27 kDa and 21 kDa, held together by non-covalent bonds, that were more active than the native enzyme. These data show that plasmin can alter CPN structure and activity, and that the C-terminal 13 kDa fragment of the CPN 83 kDa subunit is a docking peptide that is necessary to maintain the stable active tetrameric form of human CPN in plasma.