bluuebunny/crossref_metadata_2025_split huggingface dataset:
Empty nest or revolving door? A prospective study of women's quality of life in midlife during the phase of children leaving and re-entering the home
Authors: DENNERSTEIN L. , DUDLEY E. , GUTHRIE J. 
Published: October 2002

Background. This study documents changes in household composition and effects on women's quality of life of children leaving and returning home.Methods. A 9-year annual prospective study of a population-based sample of mid-aged Australian-born women who were premenopausal at baseline (N = 438) was conducted. Documentation was made of household composition and change, well-being, bothersome symptoms, daily hassles, feelings for partner and frequency of sexual activities.Results. There was an increase in the number of women living alone, and a reduction in number of households in which there were children or parents. Each year >25% of women reported a change in household composition. In the first year after the last child departed (N = 155), there was an improvement in women's positive mood and total well-being and a reduction in negative mood and the number of daily hassles. This improvement in mood was confined to those women who at baseline were not worried about children leaving home. In the first year after children return home there was a trend towards reduced frequency of sexual activities but no mood changes.Conclusions. For the majority of women, the departure of the last child from the household leads to positive changes in women's mood state and a reduced number of daily hassles. Return of offspring may have an adverse effect on sexual relating of the parents.
Inter-episodic morbidity and drop-out under carbamazepine and lithium in the maintenance treatment of bipolar disorder
Authors: KLEINDIENST N. , GREIL W. 
Published: October 2002

Background. Evaluation of mood-stabilizing treatment strategies usually focuses on their efficacy in preventing recurrences. The aim of this study is to supplement evaluation by two important aspects: inter-episodic morbidity and drop-out.Methods. Using a global outcome measure, response to prophylactic lithium and carbamazepine was evaluated in N = 171 bipolar patients (DSM-IV) participating in a randomized controlled trial with an observation period of 2½ years (MAP study).Results. The rates of re-hospitalization were similar for both treatments. However, the percentage of good clinical response (i.e. patients with a low score of inter-episodic morbidity and without both re-hospitalization and drop-out during the observation period) was significantly higher in patients randomized to lithium (40% v. 24%). This superiority of lithium resulted essentially from a lower drop-out rate in patients without re-hospitalization (17% v. 42%). Regarding severity of inter-episodic morbidity, no clear difference between the drugs was found. For both medications the predominant symptomatology was minor depressive (but not manic, mixed or schizoaffective) symptoms. In the lithium group, inter-episodic morbidity in patients without re-hospitalization significantly decreased during the first 10 months and remained on the lower level for the rest of the observation period. For carbamazepine, reduction of inter-episodic morbidity over time did not reach statistical significance. Inter-episodic morbidity was significantly related to drop-out and to re-hospitalization for both medications.Conclusion. Taking inter-episodic morbidity, drop-out and re-hospitalization into consideration, the response rate in bipolar patients (DSM-IV) was higher for prophylactic lithium than for carbamazepine. The global outcome parameter used appears to be a valuable measure of clinical response to mood stabilizing drugs.
Reversed lateralization of temporal activation during speech production in thought disordered patients with schizophrenia
Authors: KIRCHER T. T. J. , LIDDLE P. F. , BRAMMER M. J. , WILLIAMS S. C. R. , MURRAY R. M. , McGUIRE P. K. 
Published: October 2002

Background. Formal thought disorder is a core symptom of schizophrenia. It is associated with a reversed lateralization of the superior temporal cortex volume, an area that is implicated in lexical retrieval. We investigated the neural correlates of word retrieval during continuous speech in patients with formal thought disorder using functional magnetic resonance imaging (fMRI).Methods. Blood oxygenation level dependent (BOLD) contrast was measured with fMRI while six patients with schizophrenia and six healthy control subjects spoke about seven Rorschach inkblots for 3 min each. Subjects produced varying amounts of speech during each run. In a within subject design, the number of words produced was correlated with the BOLD contrast in the two runs in each participant who showed the highest variance of speech output.Results. In control subjects, the amount of speech produced was mainly correlated with activation in the left superior temporal gyrus. In the patient group, the main correlations were in the right superior temporal gyrus.Conclusions. During the production of continuous speech, patients with formal thought disorder showed a reversed laterality of activation in the superior temporal cortex. This is consistent with findings of perturbed hemispheric interaction in schizophrenia, particularly in patients with formal thought disorder.
Heavy users of acute psychiatric beds: randomized controlled trial of enhanced community management in an outer London borough
Authors: HARRISON-READ P. , LUCAS B. , TYRER P. , RAY J. , SHIPLEY K. , SIMMONDS S. , KNAPP M. , LOWIN A. , PATEL A. , HICKMAN M. 
Published: October 2002

Background. Heavy users of psychiatric services, often defined as the population that uses the most beds, consume a large part of the resources used by the whole service, despite being relatively small in number. Any intervention that reduces heavy use is therefore likely to lead to significant savings, and enhancement of standard care using a form of intensive case management akin to assertive community treatment was thought to be a pragmatic strategy for testing in this group.Methods. The effectiveness of enhanced community management (ECM) was compared with standard care alone in heavy users, who represented the 10% of patients with the highest number of hospital admissions and occupied bed days over the previous 6·5 years in an outer London borough. One hundred and ninety-three patients were randomly assigned to ECM or standard care and their use of services was determined after 1 and 2 years, with assessments of costs, clinical symptoms, needs, and social function made before entry into the study and after 1 and 2 years.Results. Despite a 2·4 fold increase in community contacts in the study group, there were no significant differences between the two groups in any of the main outcome measures. Small savings on in-patient and day-hospital service costs were counterbalanced by the increased costs of outpatient and community care for the subjects assigned to ECM. Clinical outcome data derived from interviews in two-thirds of the subjects were similar in both groups.Conclusions. Providing additional intensive community – focused care to a group of heavy users of psychiatric in-patient services in an outer London borough does not lead to any important clinical gains or reduced costs of psychiatric care.
The concordance of ICD-10 acute and transient psychosis and DSM-IV brief psychotic disorder
Authors: PILLMANN F. , HARING A. , BALZUWEIT S. , BLÖINK R. , MARNEROS A. 
Published: October 2002

Background. ICD-10 acute and transient psychotic disorder (ATPD; F23) and DSM-IV brief psychotic disorder (BPD; 298.8) are related diagnostic concepts, but little is known regarding the concordance of the two definitions.Method. During a 5-year period all in-patients with ATPD were identified; DSM-IV diagnoses were also determined. We systematically evaluated demographic and clinical features and carried out follow-up investigations at an average of 2·2 years after the index episode using standardized instruments.Results. Forty-two (4·1%) of 1036 patients treated for psychotic disorders or major affective episode fulfilled the ICD-10 criteria of ATPD. Of these, 61·9% also fulfilled the DSM-IV criteria of brief psychotic disorder; 31·0%, of schizophreniform disorder; 2·4%, of delusional disorder; and 4·8%, of psychotic disorder not otherwise specified. BPD showed significant concordance with the polymorphic subtype of ATPD, and DSM-IV schizophreniform disorder showed significant concordance with the schizophreniform subtype of ATPD. BPD patients had a significantly shorter duration of episode and more acute onset compared with those ATPD patients who did not meet the criteria of BPD (non-BPD). However, the BPD group and the non-BPD group of ATPD were remarkably similar in terms of sociodemography (especially female preponderance), course and outcome, which was rather favourable for both groups.Conclusions. DSM-IV BPD is a psychotic disorder with broad concordance with ATPD as defined by ICD-10. However, the DSM-IV time criteria for BPD may be too narrow. The group of acute psychotic disorders with good prognosis extends beyond the borders of BPD and includes a subgroup of DSM-IV schizophreniform disorder.
Different negative priming impairments in schizophrenia and subgroups of obsessive–compulsive disorder
Authors: HOENIG K. , HOCHREIN A. , MÜLLER D. J. , WAGNER M. 
Published: October 2002

Background. Inhibitory functioning is assumed to be deficient in some psychiatric disorders, most notably in patients with schizophrenia and obsessive–compulsive disorder (OCD). In order to investigate inhibitory functioning, priming tasks are commonly used. The present paradigm offers the opportunity to isolate specific distractor features (identity, location) for independent examination.Methods. Negative priming (NP) for stimulus identity and location was examined in patients with schizophrenia (N = 16), patients with OCD (N = 15) and matched controls (N = 16). All groups performed a referent size-selection task in which they were instructed successively to select the larger one of two cardinal numbers. The deeper processing of both stimuli was expected to yield large NP effects that allow the detection of subtle group differences.Results. Large NP effects were found for stimulus identity in all three groups. Schizophrenic patients differed from normal controls with respect to the amount of incidental location priming. Subgroup analyses of OCD patients showed NP impairments for checkers when the response–stimulus interval (RSI) was short, but large identity NP when the RSI was long. OCD non-checkers showed normal NP patterns with short RSI, but reduced identity NP with longer RSI.Conclusions. Schizophrenic patients do not show the ability to use spatial selective attention in order to guide their actions as shown by normal controls. Information processing was differentially impaired in OCD subgroups (checkers and non-checkers) dependent on RSI variation. This result supports those studies that found reduced NP in OCD patients and points to the necessity of differential subgroup studies.
Characterizing the effects of sertraline in post-traumatic stress disorder
Authors: DAVIDSON J. R. T. , LANDERMAN L. R. , FARFEL G. M. , CLARY C. M. 
Published: October 2002

Background. Sertraline has a proved efficacy in post-traumatic stress disorder (PTSD), but it is unknown which symptoms respond or in what sequence this occurs. Such information might be useful clinically and heuristically.Method. The study examined the effects of sertraline on the individual symptoms of PTSD. It also examined whether early changes in anger explained drug-induced change in other symptoms over time. Mixed models analysis was applied to datasets from two 12-week placebo-controlled trials of sertraline. A validated self-rating scale (DTS) was used to assess treatment efficacy.Results. Sertraline was superior to placebo on 15 of 17 symptoms, especially in the numbing and hyperarousal clusters. A strong effect was found on anger from week 1, which partly explained the subsequent effects of sertraline on other symptoms, some of which began to show significantly greater response to drug than to placebo at week 6 (emotional upset at reminders, anhedonia, detachment, numbness, hypervigilance) and week 10 (avoidance of activities, foreshortened future).Conclusions. Sertraline exercises a broad spectrum effect in PTSD. Effects are more apparent on the psychological rather than somatic symptoms of PTSD, with an early modulation of anger and, perhaps, other affects, preceding improvement in other symptoms.
Pharmacological characterization of the chemokine receptor, hCCR1 in a stable transfectant and differentiated HL‐60 cells: antagonism of hCCR1 activation by MIP‐1β
Authors: Chou Chuan‐Chu , Fine Jay S , Pugliese‐Sivo Catherine , Gonsiorek Waldemar , Davies Liza , Deno Gregory , Petro Mary , Schwarz Martin , Zavodny Paul J , Hipkin R William 
Published: October 2002

C‐C chemokine receptor‐1 (CCR1) has been implicated in mediating a variety of inflammatory conditions including multiple sclerosis and organ rejection. Although originally referred to as the MIP‐1α/RANTES receptor, CCR1 is quite promiscuous and can be activated by numerous chemokines.
We used radioligand binding and [35S]‐GTPγS exchange assays in membranes from a cell line transfected to express CCR1 (Ba/F3‐hCCR1) to characterize a panel of chemokines (HCC‐1, MIP‐1α, MIP‐1β, MIP‐1δ, MPIF‐1, MCP‐2, MCP‐3, and RANTES) as CCR1 ligands. In this recombinant model, these chemokines displaced 125I‐MIP‐1α with a wide range of potencies and, with the exception of MCP‐2, acted as full agonists in stimulating [35S]‐GTPγS exchange.
We then assessed the utility of HL‐60 cells cultured with known differentiating agents (PMA, DMSO, dibutyryl‐cAMP or retinoic acid) for investigating CCR1 pharmacology. In [35S]‐GTPγS exchange assays, membranes from cells cultured with retinoic acid (4–6 days) were the most responsive to activation by MIP‐1α and MPIF‐1. FACS analysis and comparative pharmacology confirmed that these activities were mediated by CCR1.
Using [35S]‐GTPγS exchange assays, intracellular calcium flux and/or whole cell chemotaxis assays in HL‐60(Rx) cells, we validated that MIP‐1α was the most potent CCR1 ligand (MIP‐1α>MPIF‐1>RANTESMIP‐1β) although the ligands differed in their efficacy as agonists. MPIF‐1 was the more efficacious (MPIF‐1>RANTES=MIP‐1α>>MIP‐1β). 125I‐MIP‐1β binding in Ba/F3‐hCCR1 and HL‐60(Rx) membranes was competitively displaced by MIP‐1α, MPIF‐1 and MIP‐1β. The binding Ki for these chemokines with 125I‐MIP‐1β were essentially identical in the two membrane systems.
Lastly, MIP‐1β antagonized [35S]‐GTPγS exchange, Ca2+ flux and chemotaxis in HL‐60(Rx) cells in response to robust agonists such as MIP‐1α, RANTES and MPIF‐1. Based on our results, we propose that MIP‐1β could function as an endogenous inhibitor of CCR1 function.

British Journal of Pharmacology (2002) 137, 663–675. doi:10.1038/sj.bjp.0704907
A novelβ‐sheet breaker, RS‐0406, reverses amyloidβ‐induced cytotoxicity and impairment of long‐term potentiationin vitro
Authors: Nakagami Yasuhiro , Nishimura Satoko , Murasugi Takako , Kaneko Isao , Meguro Masaki , Marumoto Shinji , Kogen Hiroshi , Koyama Kazuo , Oda Tomiichiro 
Published: October 2002

Fibril formation of amyloid β peptide (Aβ) is considered to be responsible for the pathology of Alzheimer's disease (AD). The Aβ fibril is formed by a protein misfolding process in which intermolecular β‐sheet interactions become stabilized abnormally. Thus, to develop potential anti‐AD drugs, we screened an in‐house library to find compounds which have a profile as a β‐sheet breaker.We searched for a β‐sheet breaker profile in an in‐house library of approximately 113,000 compounds. From among the screening hits, we focused onN,N′‐bis(3‐hydroxyphenyl)pyridazine‐3,6‐diamine (named RS‐0406), which had been newly synthesized in our laboratory. This compound (10–100 μg ml−1) was found to be capable of significantly inhibiting 25 μMAβ1–42fibrillogenesis and, furthermore, disassembling preformed Aβ1–42fibrilsin vitro.We then investigated the effect of RS‐0406 on 111 nMAβ1–42‐induced cytotoxicity in primary hippocampal neurons, and found that 0.3–3 μg ml−1RS‐0406 ameliorates the cytotoxicity. Moreover, 3 μg ml−1RS‐0406 reversed 1 μMAβ1–42‐induced impairment of long‐term potentiation in hippocampal slices.In this study, we have succeeded in identifying RS‐0406 which has potential to inhibit Aβ1–42fibrillogenesis, and to protect neurons against Aβ1–42‐induced biological toxicityin vitro. These results suggest that RS‐0406 or one of the derivatives could become a therapeutic agent for AD patients.British Journal of Pharmacology(2002)137, 676–682. doi:10.1038/sj.bjp.0704911
Propofol prevents endothelial dysfunction induced by glucose overload
Authors: Karashima Yuji , Oike Masahiro , Takahashi Shosuke , Ito Yushi 
Published: October 2002

Surgical operations often induce acute hyperglycemia, which is known to affect endothelial functions. In this study, we examined the effects of propofol, a commonly used general anaesthetic, on bovine aortic endothelial cell (BAEC) dysfunction induced by glucose overload.
D‐glucose overload (23 mM) induced an accumulation of superoxide anion (O2−), assessed by MCLA chemiluminescence, to a similar extent as that generated by 233 μU ml−1 xanthine oxidase (XO) and 100 μM xanthine. Propofol inhibited this accumulation with an IC50 of 0.21 μM, whereas much higher concentrations of propofol were required to scavenge O2− generated by 250 μU ml−1 XO and 100 μM xanthine (IC50: 13.5 μM).
D‐glucose overload attenuated ATP‐induced NO production which was detected using diaminofluorescence‐2 (DAF‐2). The inhibition was reversed by propofol with an EC50 of 0.60 μM. In contrast, inhibitions caused by xanthine/XO were not altered by propofol (1 μM).
D‐glucose overload suppressed ATP‐induced Ca2+ oscillations and capacitative Ca2+ entry (CCE), which were both restored by superoxide dismutase, indicating that O2− was responsible. Propofol restored these attenuated Ca2+ oscillations and CCE with EC50 of 0.31 and 1.0 μM, respectively.
D‐glucose overload (23 mM) increased the intracellular glucose concentration 4 fold, compared with cells exposed to 5.75 mM glucose, and 1 μM propofol reduced this increase to 2.8 fold.
We conclude from these results that anaesthetic concentrations of propofol prevent the impairment of Ca2+‐dependent NO production in BAEC induced by glucose overload. This effect is mainly due to the reduction of O2− accumulation, and involves, at least in part, the inhibition of cellular glucose uptake.

British Journal of Pharmacology (2002) 137, 683–691. doi:10.1038/sj.bjp.0704912
Is urotensin‐II the new endothelin?
Authors: Maguire Janet J , Davenport Anthony P 
Published: October 2002

Urotensin‐II (U‐II), a peptide isolated from the urophysis of teleost fish 35 years ago, is the endogenous ligand of the mammalian orphan receptor GPR14/SENR. Recently, human homologues of both the receptor (UT‐II) and the peptide (hU‐II) have been discovered. Following de‐orphanization, hU‐II was declared the ‘new endothelin’ as initial studies suggested similarities between the peptides, and in isolated arteries of cynomolgus monkey U‐II was a more potent constrictor than endothelin‐1 (ET‐1), with equal efficacy. However, effects of U‐II in vascular tissue from other mammalian species are variable and although potent, U‐II exhibits a lesser maximal response than ET‐1. In contrast, in humans U‐II has emerged as a ubiquitious constrictor of both arteries and veins in vitro and elicits a reduction in blood flow in the forearm and skin microcirculation in vivo. In addition to direct vasoconstrictor activity on smooth muscle receptors, endothelium‐dependent U‐II‐mediated vasodilatation has also been observed. Non‐vascular, peripheral actions of U‐II include potent inotropy and airway smooth muscle constriction and U‐II and its receptor are present throughout rat brain implying a possible neurotransmitter or neuromodulatory role in the central nervous system. U‐II is proposed to contribute to human diseases including atherosclerosis, cardiac hypertrophy, pulmonary hypertension and tumour growth. The development of selective receptor antagonists should help to clarify the relative importance of hU‐II as a multifunctional peptide in mammalian systems and its role in disease. What is clear is that U‐II is emerging as a new and potentially important mammalian transmitter.British Journal of Pharmacology (2002) 137, 579–588. doi:10.1038/sj.bjp.0704924
Sequence analysis of an artificial family of RNA‐binding peptides
Authors: Barrick Jeffrey E. , Roberts Richard W. 
Published: October 2002

AbstractDiverse peptide sequences recognizing the λ boxB RNA hairpin were previously isolated from a library encoding the 22‐residue λ N peptide with random amino acids at positions 13–22 using mRNA display. We have statistically analyzed amino acid distributions in 65 unique sequences from rounds 11 and 12 of this selection and evaluated the resulting structural and functional predictions by alanine‐scanning mutagenesis and circular dichroism spectrometry. This artificial sequence family has a consensus structure that continues the bent α helix of λ N up to position 17 when bound to λ boxB. A charge pair (E14R15) and hydrophobic patch (A21L22or V21L22) have important functional roles in this context. Notably, amino acid covariance reveals six specific pairs of random region positions with >95% significant linkage and strong overall helical (i+1, i+3, and i+4) couplings. The covariance analysis suggests that (1) the sequence context of every residue in each insert has been optimized, (2) selected sequences are local optima on a rugged fitness landscape, and (3) it is possible to detect more subtle structural features with artificial protein sequence families than natural homologs. Our results provide a framework for investigating the structures of in vitro selected proteins by functional minimization, reselection, and covariance analysis.
α‐Crystallin and ATP facilitate the in vitro renaturation of xylanase: enhancement of refolding by metal ions
Authors: Nath Devyani , Rawat Urmila , Anish Ramakrishnan , Rao Mala 
Published: October 2002

Abstractα‐Crystallin is a multimeric protein that functions as a molecular chaperone and shares extensive structural homology to small heat shock proteins. For the functional in vitro analysis of α‐crystallin, the xylanase Xyl II from alkalophilic thermophilic Bacillus was used as a model system. The mechanism of chaperone action of α‐crystallin is less investigated. Here we studied the refolding of Gdn HCl‐denatured Xyl II in the presence and absence of α‐crystallin to elucidate the molecular mechanism of chaperone‐mediated in vitro folding. Our results, based on intrinsic tryptophan fluorescence and hydrophobic fluorophore 8‐anilino‐1‐naphthalene sulfonate binding studies, suggest that α‐crystallin formed a complex with a putative molten globule‐like intermediate in the refolding pathway of Xyl II. The α‐crystallin•Xyl II complex exhibited no functional activity. Addition of ATP to the complex initiated the renaturation of Xyl II with 30%–35% recovery of activity. The nonhydrolyzable analog 5′‐adenylyl imidodiphosphate (AMP‐PNP) was capable of reconstitution of active Xyl II to a lesser extent than ATP. Although the presence of Ca2+ was not required for the in vitro refolding of Xyl II, the renaturation yield was enhanced in its presence. Experimental evidence indicated that the binding of ATP to the α‐crystallin•Xyl II complex brought about conformational changes in α‐crystallin facilitating the dissociation of xylanase molecules. This is the first report of the enhancement of α‐crystallin chaperone functions by metal ions.