bluuebunny/crossref_metadata_2025 huggingface dataset:
Service provision for elderly depressed persons and political and professional awareness for this subject: a comparison of six European countries
Authors: Bramesfeld Anke
Published: May 2003

Objective

Under‐treatment of depression in late‐life is a subject of rising public health concern throughout Europe. This study investigates and compares the availability of services for depressed elderly persons in Denmark, France, Germany, Sweden, Switzerland and the UK. Additionally, it explores factors that might contribute to an adequate services supply for depressed elderly people.

Method

Review of the literature and guide supported expert interviews. Analysis of the practice of care provision for depressed elderly persons and of indicators for political and professional awareness, such as university chairs, certification processes and political programmes in gerontopsychiatry.

Results

Only Switzerland and the UK offer countrywide community‐oriented services for depressed elderly persons. Clinical experience in treating depression in late‐life is not regularly acquired in the vocational training of the concerned professionals. Indicators suggest that the ‘medical society’ and health politics in Switzerland and the UK regard psychiatric disease in the elderly more importantly than it is the case in the other investigated countries.

Conclusions

Service provision for depressed elderly persons seems to be more elaborated and better available in countries where gerontopsychiatry is institutionalised to a greater extend in the ‘medical society’ and health politics. Copyright © 2003 John Wiley & Sons, Ltd.
The early stage of vascular dementia: significance of a complete therapeutic program
Authors: Kruglov L. S.
Published: May 2003

Theory

Mild manifestations of vascular dementia are relatively widespread among the old‐age population. Drug therapy for this disorder is insufficiently effective at present, making it necessary to improve the treatment of such patients by means of an adequate psychotherapeutic and rehabilitation program.

Aims

To assess the role of psychotherapeutic and rehabilitation measures in improving outcome in the early stage of vascular dementia.

Methods

The test and control cohorts (each n = 95) were matched for characteristics found to be significant for outcome of treatment (the relevant predictors were found using Multiple Regression Analysis). The cohorts differed in the amount of the psychotherapy and rehabilitation received. To assess the effects of treatment the SCAG scale and a special scale for evaluating the level of activity in the household were used.

Results

In the test cohort the patients' condition improved significantly compared with the controls. Even in case of only slight therapeutic reduction of psychopathologic symptoms the systematic use of psychotherapeutic and rehabilitation methods favoured preserving a certain level of activity in the household and for some patients even improving it.

Conclusions

The results of therapy at the early stage of vascular dementia to a great extent depend on carrying out a full‐scale psychotherapeutic and rehabilitation program. The positive significance of the latter is connected not only with improvement of clinical indices but also with direct optimizing the every day life activity level. Copyright © 2003 John Wiley & Sons, Ltd.
CSF phosphorylated tau—does it constitute an accurate biological test for Alzheimer's disease?
Authors: Mitchell Alex , Brindle Nick
Published: May 2003

Introduction

There is considerable interest in developing a diagnostic test which could differentiate between early Alzheimer's disease (AD) and other causes of memory impairment with more than 80% sensitivity and 80% specificity.

Objective

To review the studies that have examined CSF phosphorylated tau as diagnostic test of AD vs clinically representative comparison groups.

Method

A critical review of the literature using Embase, Web of Science, Medline and Psychinfo databases supplemented by handsearching and contact with experts in the field.

Results

CSF phosphorylated tau is a marker of AD that improves upon the utility of CSF total tau and clinical examination alone. Studies have found high levels of tau phosphorylated at Threonine 231 and/or Serine 199 in AD but not in other causes of dementia, in depression or in healthy elderly controls. Of particular interest, the test appears equally valid in cases of early AD as in moderate or late stages and may also be of use in predicting future decline in subjects with mild cognitive impairment.

Conclusion

CSF phosphorylated tau is a promising diagnostic test for AD but this requires replication using pathologically confirmed cases. Copyright © 2003 John Wiley & Sons, Ltd.
Prevalence of sub‐threshold depression in elderly patients with chronic obstructive pulmonary disease
Authors: Yohannes Abebaw M. , Baldwin Robert C. , Connolly Martin J.
Published: May 2003

Objectives

We hypothesized that COPD patients with sub‐threshold depression would have levels of disability and impaired quality of life approaching that for major depression and significantly greater than for non‐depressed COPD patients.

Setting

A university teaching hospital

Method

137 outpatients (69 men), with a mean age of 73 years (range 60–89 years) with symptomatic irreversible, moderate to severe COPD were recruited. Subjects were interviewed using the Geriatric Mental State Schedule (GMS), a structured psychiatric interview schedule, along with its diagnostic algorithm AGECAT. A GMS/AGECAT score of 3 or more is indicative of a case‐level of depression, a GMS/AGECAT score of 1–2 indicates sub‐threshold depression and GMS/AGECAT of 0, no depression. Physical disability was measured by the Manchester Respiratory Activities of Daily Living questionnaire (MRADL) and quality of life was assessed by the Breathing Problems Questionnaire (BPQ).

Results

Mean (SD) one second forced expiratory volume was 0.89 (0.33) litres. The prevalence of GMS/AGECAT case‐level depression (≥ 3) was 57 cases (42%); of GMS/AGECAT sub‐threshold depression (1–2) 34 (25%); and GMS/AGECAT non‐depression (0) 46 (33%). Comparison of MRADL score in the three groups (mean, 95% confidence intervals) revealed [GMS ≥ 3 = 9.9 (8.4 to 11.3) vs GMS = 1–2, 12.9 (11.2 to 14.4) vs GMS = 0, 15.6 (14 to 16.6) p < 0.0001]. BPQ scores (mean, 95% confidence intervals) showed [GMS ≥ 3 = 54 (50 to 57) vs GMS = 1–2, 40 (36.3 to 44) GMS = 0, 33 (30.6 to 36.7) p < 0.0001]. There was no significant difference in FEV1 between the three groups.

Conclusion

Sub‐threshold depression accounted for 25% of the sample. In this study disability associated with sub‐threshold depression in patients with COPD was intermediate to that associated with case‐level depression and no with depression and significantly worse than in the latter group. Sub‐threshold depression is associated with substantial morbidity in COPD. Copyright © 2003 John Wiley & Sons, Ltd.
Phantom boarder symptom in dementia
Authors: Hwang Jen‐Ping , Yang Chen‐Hong , Tsai Shih‐Jen
Published: May 2003

Objective

Phantom boarder symptom (PBS), which has been labelled a misidentification and is commonly observed in cases of Alzheimer's disease, is the perceptual dysfunction where it is imagined that there are people in the home. It may also be encountered in cases of vascular dementia and other variants of this cognitive dysfunction. This study was undertaken to investigate PBS frequency and characteristics for a sample of dementia inpatients, and to determine the strength of the association with other psychotic symptoms.

Methods

The sample population consisted of 240 dementia patients admitted to our geropsychiatric ward. Patients with and without PBS were compared in terms of general characteristics and psychotic symptoms.

Results

Of the 240 dementia patients, PBS was identified in 56 (23.3%). There were no significant gender differences between the PBS and non‐PBS groups. Means for age and onset‐age were higher for the PBS group, and the prevalence of hallucinations and other misidentifications was greater compared to the non‐PBS analog. Occurrence of PBS was not significantly associated with delusions or physical aggression.

Conclusions

PBS is a common symptom in dementia of various etiologies. Our association findings suggest that it may be more productive to classify PBS as a type of misidentification, instead of as a delusion. Copyright © 2003 John Wiley & Sons, Ltd.
Antidepressant‐associated mania in late life
Authors: Young R. C. , Jain H. , Kiosses D. N. , Meyers B. S.
Published: May 2003

Background

Elderly patients can present with mania for the first time late in life, and some elders treated with antidepressants can present with mania. Clinical characteristics of antidepressant‐associated mania (AAM) in late life have not been examined.

Objectives

The aims of the study were to identify elders with AAM and to compare selected clinical characteristics to those of manic elders who had not been treated with an antidepressant. We hypothesized that AAM patients would have later age at presentation of bipolar disorder.

Methods

We retrospectively reviewed inpatients with manic disorder who were aged ≥60 years. The sample was selected from admissions prior to 1990.

Results

AAM patients (n = 11) were more often experiencing first manic episode, and they had later age at onset of first manic episode, compared to non‐AAM patients (n = 46). Most of the AAM patients had been treated with tricyclic agents.

Conclusions

These preliminary findings invite further investigation. Related studies may contribute to risk‐benefit analyses for the use of particular antidepressants in the elderly. Also, first episode mania in late life may prove to be a useful model of vulnerability to AAM. Copyright © 2003 John Wiley & Sons, Ltd.
Does aspirin affect outcome in vascular dementia? A retrospective case‐notes analysis
Authors: Devine M. E. , Rands G.
Published: May 2003

Background

Ischaemic vascular dementia shares risk factors with stroke. There is evidence that control of these risk factors may prevent or alter the course of vascular dementia.

Objective

To assess the effect of regular low‐dose aspirin on outcomes for patients with vascular dementia.

Design

Retrospective analysis of hospital case‐notes with further outcome information from telephone calls to general practitioners, social services and institutions. Comparison of outcomes for aspirin‐treated and untreated patients.

Setting

One North London NHS Trust.

Patients

Seventy‐eight patients with clinician's diagnosis of ischaemic vascular dementia, discharged from acute inpatient units between 1 January 1995 and 31 December 1997; 38 on aspirin.

Main outcome measures

Survival times from dementia onset to institutionalization and death.

Results

Median survival time to institutionalization was 28 months and to death was 52 months. There was no overall difference between aspirin and non‐aspirin groups for these outcomes. When data were stratified for social status, i.e. living alone or with carer when last at home, differences emerged for those living with carer. Aspirin was associated with a trend towards increased time to institutionalization (39 vs 22 months, p < 0.09) and a significant advantage in time to death (71 vs 27 months, p = 0.02). These effects were non‐significant after statistical adjustment for confounding variables.

Conclusions

The results support but do not prove a role for regular, low‐dose aspirin in improving both life expectancy and survival at home for patients with vascular dementia. Compliance may be better in those living with a carer. Larger, prospective studies should be performed to confirm these findings. Cognitive and behavioural outcomes should also be studied. Copyright © 2003 John Wiley & Sons, Ltd.
The effect of Qigong on general and psychosocial health of elderly with chronic physical illnesses: a randomized clinical trial
Authors: Tsang Hector W. H. , Mok C. K. , Au Yeung Y. T. , Chan Samuel Y. C.
Published: May 2003

Objectives

Based on the model by Tsang et al. (2002) which summarized the etiological factors and consequences of depression in elderly with chronic physical illnesses, a randomized clinical trial of a special form of Qigong (The Eight Section Brocades) was conducted to assess if it improved the biopsychosocial health of participants.

Design

50 geriatric patients in sub‐acute stage of chronic physical illnesses were recruited and randomly assigned into the intervention and control group. The intervention group was given a 12‐week period of Qigong practice while the control group was given traditional remedial rehabilitation activities.

Results

The intervention group participants expressed improvement in physical health, ADL, psychological health, social relationship, and health in general as reflected by scores of the Perceived Benefit Questionnaire and informal feedback.

Conclusion

Although results are not significant in the generalization measures, it may be due to small effect size, small sample size, and short intervention period. Although not all of the hypotheses are supported, this report shows that Qigong (the Eight Section Brocades) is promising as an alternative intervention for elderly with chronic physical illness to improve their biopsychosocial health. More systematic evaluation with larger sample size and longer period of intervention is now underway in Hong Kong. Results will be reported once available. Copyright © 2003 John Wiley & Sons, Ltd.
The impact upon extra‐pyramidal side effects, clinical symptoms and quality of life of a switch from conventional to atypical antipsychotics (risperidone or olanzapine) in elderly patients with schizophrenia
Authors: Ritchie C. W. , Chiu E. , Harrigan S. , Hall K. , Hassett A. , Macfarlane S. , Mastwyk M. , O'Connor D. W. , Opie J. , Ames D.
Published: May 2003

Background

Atypical antipsychotics are commonly used in the management of schizophrenia in late life with evidence suggesting they induce lower rates of motor disturbance, but have similar efficacy to conventional antipsychotics. Trials in the elderly have been either retrospective, small, of short duration or of a single‐arm design.

Aims

To demonstrate the effects upon motor side‐effects, efficacy, safety and quality of life (QOL) of switching elderly patients with schizophrenia from conventional antipsychotics to olanzapine or risperidone.

Methods

Elderly patients with schizophrenia were randomly allocated to olanzapine or risperidone and followed through an open‐label crossover period. Between and within group intention to treat analyses were conducted.

Results

66 patients were randomised (mean age 69.6 [SD ± 6.2]). Four (11.8%) patients on olanzapine and 8 (26.7%) patients on risperidone failed to complete the crossover because of treatment failure [Odds Ratio (OR) = 2.73[0.73–10.2] p = 0.14]. The mean doses upon completion of switching in each arm were 9.9 mg (SD = 4.2) and 1.7 mg (SD = 1.2) for olanzapine and risperidone respectively. In both arms there was improvement in Parkinsonism, though only olanzapine was associated with a reduction in dyskinetic symptoms. The Brief Psychiatric Rating Scale, Scale for the assessment of Negative Symptoms and Montgomery and Asberg Depression Rating Scale scores all improved through the crossover period in both arms with no between group differences. Treatment with olanzapine was associated with a better response over risperidone on the psychological domain of the World Health Organisation—Quality Of Life [Brief] (WHO‐QOL‐BREF) scale ( p = 0.02). Patients in the olanzapine arm also demonstrated improvement from baseline in the WHO‐QOL‐BREF physical, psychological and health satisfaction domains, but risperidone had no effect on any Quality of Life (QOL) measure.

Conclusions

After switching from a conventional antipsychotic, olanzapine and risperidone were associated with improvement in core symptoms of schizophrenia and motor side effects. Subjects switched to olanzapine were more likely to complete the switching process and show an improvement in psychological QOL. Copyright © 2003 John Wiley & Sons, Ltd.
A population based study on the intra and inter‐rater reliability of the clock drawing test in Brazil: the Bambuí Health and Ageing Study
Authors: Fuzikawa Cíntia , Lima‐Costa Maria Fernanda , Uchoa Elizabeth , Barreto Sandhi Maria , Shulman Ken
Published: May 2003

Background

Reliability should be considered when selecting a scoring system since it influences validity. CDT reliability has rarely been assessed in population based studies and in developing countries. The aim of the present study was to determine intra and inter–rater reliabilities of the CDT scored by the Shulman (2000) method, in elderly with very low formal educational level from Brazil.

Methods

CDTs performed by a random sample of 202 subjects of a population‐based cohort of elderly were scored on two occasions by the same rater and by two independent raters. Reliability was measured using the kappa statistic, weighted kappa and the intraclass correlation coefficient. Data were stratified according to gender, age and schooling level.

Results

Intra and inter–rater reliabilities were excellent when CDTs were classified as ‘normal’ (scores 4 or 5) or ‘abnormal’ (scores 0 to 3) (kappa = 0.99 and 0.94, respectively) and were in the good to excellent range when scored from 0 to 5 (kappa = 0.88 and 0.74, respectively). Difficulties in distinguishing between scores 4 and 5, and a low proportion of score 1 tests were found.

Conclusions

The CDT scored by the Shulman (2000) method appears to have good to excellent reliability in an elderly population with very low formal educational level. However, difficulties in distinguishing between scores 4 and 5, and a low proportion of score 1 tests suggest these scores may not be totally adequate for this population. Further studies are necessary to determine the consistency of our results in similar populations. Copyright © 2003 John Wiley & Sons, Ltd.
Asymmetry of the brain surface from deformation field analysis
Authors: Lancaster Jack L. , Kochunov Peter V. , Thompson Paul M. , Toga Arthur W. , Fox Peter T.
Published: May 2003

The detection of asymmetry of exposed brain surfaces is examined, and a new method, deformation‐based asymmetry (DBA), is introduced. DBA is based on analysis of two high‐resolution magnetic resonance brain images, each with features representative of the subject group from which they were derived. Warping of individual brain images to their group representative image using octree spatial normalization provides sets of displacement vectors that are used in estimating deformation variance. For DBA group‐representative left and right hemisphere images are compared. Representative hemisphere images are warped to each other and asymmetry analyzed using standardized d‐values calculated as the ratio of displacement vector magnitude to the estimated component of variance in the direction of the displacement vector for each surface voxel. D‐values were calculated within hemispheres by dividing subjects into two equal groups and comparing left‐to‐left and right‐to‐right. D‐values from this ipsilateral hemisphere grouping were pooled. D‐values from contralateral hemispheres were compared with the pooled ipsilateral hemisphere data. The proportion of d‐values above a fixed level was used to test for difference between the two groups. High‐resolution magnetic resonance (MR) images from 20 young, right‐handed males were studied using DBA. No significant differences were seen between sub‐grouped ipsilateral d‐values (P > 0.10). Highly significant asymmetries (P < 0.0001) were found between hemispheres, and in each lobe. Common right frontal and left occipital petalias were seen. The DBA method can theoretically be applied to any two groups of globally similar structures where analysis of dissimilarity of regional features is sought. Hum. Brain Mapping 19:79–89, 2003. © 2003 Wiley‐Liss, Inc.
Nonlinear synchronization in EEG and whole‐head MEG recordings of healthy subjects
Authors: Stam Cornelis J. , Breakspear Michael , van Walsum Anne‐Marie van Cappellen , van Dijk Bob W.
Published: May 2003

According to Friston, brain dynamics can be modelled as a large ensemble of coupled nonlinear dynamical subsystems with unstable and transient dynamics. In the present study, two predictions from this model (the existence of nonlinear synchronization between macroscopic field potentials and itinerant nonlinear dynamics) were investigated. The dependence of nonlinearity on the method of measuring brain activity (EEG vs. MEG) was also investigated. Dataset I consisted of 10 MEG recordings in 10 healthy subjects. Dataset II consisted of simultaneously recorded MEG (126 channels) and EEG (19 channels) in 5 healthy subjects. Nonlinear coupling was assessed with the synchronization likelihood S and dynamic itinerancy with the synchronization entropy Hs. Significance was assessed with a bootstrap procedure (“surrogate data testing”), comparing S and Hs with their distribution under the null hypothesis of stationary, linear dynamics. Significant nonlinear synchronization was detected in 14 of 15 subjects. The nonlinear dynamics were associated with a high index of itinerant behaviour. Nonlinear interdependence was significantly more apparent in MEG data than EEG. Synchronous oscillations in MEG and EEG recordings contain a significant nonlinear component that exhibits characteristics of unstable and itinerant behaviour. These findings are in line with Friston's proposal that the brain can be conceived as a large ensemble of coupled nonlinear dynamical subsystems with labile and unstable dynamics. The spatial scale and physical properties of MEG acquisition may increase the sensitivity of the data to underlying nonlinear structure. Hum. Brain Mapping 19:63–78, 2003. © 2003 Wiley‐Liss, Inc.
Effects of age and speed of processing on rCBF correlates of syntactic processing in sentence comprehension
Authors: Caplan David , Waters Gloria , Alpert Nathaniel
Published: May 2003

Positron emission tomography (PET) was used to determine the effect of age on regional cerebral blood flow (rCBF) during syntactic processing in sentence comprehension. PET activity associated with making plausibility judgments about syntactically more complex subject object (SO) sentences (e.g., The juice that the child spilled stained the rug) was compared to that associated with making judgments about synonymous syntactically simpler object subject (OS) sentences (e.g., The child spilled the juice that stained the rug). In the first study, 13 elderly (70–80‐year‐old) subjects showed increased rCBF in the left inferior parietal lobe. This result contrasted with previous studies, which have shown activation in Broca's area in this task in young subjects. Elderly subjects were noted to have longer reaction times than young subjects previously tested. A second study found that young subjects whose reaction times were as long as those of the elderly subjects tested in Experiment 1 activated left superior parietal, and not left inferior frontal, structures. A third experiment found that elderly subjects with reaction times as fast as previously tested young subjects activated left inferior frontal structures. The results suggest that the speed of syntactic processing, but not age per se is related to the neural location where one aspect of syntactic processing is carried out. Hum. Brain Mapping 19:112–131, 2003. © 2003 Wiley‐Liss, Inc.
More “mapping” in brain mapping: Statistical comparison of effects
Authors: Jernigan Terry L. , Gamst Anthony C. , Fennema‐Notestine Christine , Ostergaard Arne L.
Published: May 2003

The term “mapping” in the context of brain imaging conveys to most the concept of localization; that is, a brain map is meant to reveal a relationship between some condition or parameter and specific sites within the brain. However, in reality, conventional voxel‐based maps of brain function, or for that matter of brain structure, are generally constructed using analyses that yield no basis for inferences regarding the spatial nonuniformity of the effects. In the normal analysis path for functional images, for example, there is nowhere a statistical comparison of the observed effect in any voxel relative to that in any other voxel. Under these circumstances, strictly speaking, the presence of significant activation serves as a legitimate basis only for inferences about the brain as a unit. In their discussion of results, investigators rarely are content to confirm the brain's role, and instead generally prefer to interpret the spatial patterns they have observed. Since “pattern” implies nonuniform effects over the map, this is equivalent to interpreting results without bothering to test their significance, a practice most of the experimentally‐trained would eschew in other contexts. In this review, we appeal to investigators to adopt a new standard of data presentation that facilitates comparison of effects across the map. Evidence for sufficient effect size difference between the effects in structures of interest should be a prerequisite to the interpretation of spatial patterns of activation. Hum. Brain Mapping 19:90–95, 2003. © 2003 Wiley‐Liss, Inc.
A wavelet‐based approximation of surface coil sensitivity profiles for correction of image intensity inhomogeneity and parallel imaging reconstruction
Authors: Lin Fa‐Hsuan , Chen Ying‐Jui , Belliveau John W. , Wald Lawrence L.
Published: May 2003

We evaluate a wavelet‐based algorithm to estimate the coil sensitivity modulation from surface coils. This information is used to improve the image homogeneity of magnetic resonance imaging when a surface coil is used for reception, and to increase image encoding speed by reconstructing images from under‐sampled (aliased) acquisitions using parallel magnetic resonance imaging (MRI) methods for higher spatiotemporal image resolutions. The proposed algorithm estimates the spatial sensitivity profile of surface coils from the original anatomical images directly without using the body coil for additional reference scans or using coil position markers for electromagnetic model‐based calculations. No prior knowledge about the anatomy is required for the application of the algorithm. The estimation of the coil sensitivity profile based on the wavelet transform of the original image data was found to provide a robust method for removing the slowly varying spatial sensitivity pattern of the surface coil image and recovering full FOV images from two‐fold acceleration in 8‐channel parallel MRI. The results, using bi‐orthogonal Daubechies 97 wavelets and other members in this family, are evaluated for T1‐weighted and T2‐weighted brain imaging. Hum. Brain Mapping 19:96–111, 2003. © 2003 Wiley‐Liss, Inc.
The design and synthesis of β‐trifluoromethylenol phosphates as potential insecticides
Authors: Ding Yixiang , Huang Xiaogen
Published: May 2003

A new group of compounds, β‐trifluoromethylenol phosphates [(RO)2P(O)OCRCHCF3], has been designed and prepared by several methods. Some of them showed good insecticidal activities. In the molecular structure, the designed leaving group can rearrange to a powerful electrophilic agent, β,β‐difluorovinyl ketone, which would be a potential enzyme inhibitor. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:304–308, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10147
2,4,6‐Trialkylphenyl‐2H‐phospholes from slightly aromatic 1H‐phospholes and their use in [4 + 2] cycloaddition reactions
Authors: Keglevich György , Farkas Renáta , Imre Tímea , Ludányi Krisztina , Szöllősy Áron , Tőke László
Published: May 2003

1‐(2,4,6‐Trialkylphenyl)phospholes 1a,b possess a moderate aromatic character. Despite of that they underwent a sigmatropic rearrangement at 150°C to afford 2H‐phospholes 2a,b which by trapping with tolane, or in reaction with another unit of 2 gave [4 + 2] cycloadducts 3a,b, or in a reversible reaction, dimer 6, respectively. Dedimerization of species 6 at 150°C in the presence of tolane, or at 0°C under oxidative circumstances, led to 1‐phosphanorbornadiene 3a, or phosphole oxide dimer 8, respectively. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:316–319, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10151
Chemo‐ and regioselective allylic oxidation: Oxo‐derivatives of 2‐phospholene sugar analogs
Authors: Reddy Valluru Krishna , Rao Lakonda Nagaprasada , Maeda Motoki , Haritha Buchammagari , Yamashita Mitsuji
Published: May 2003

A convenient and facile chemo‐ and regioselective oxidation of the allylic methylene group in a 2‐phospholene ring system afforded the novel carbonyl derivatives of 2‐phospholenes (2a–i). The method gives high conversion and selectivity in the formation of allylic ketones. The advantages of this oxidation method in such a five‐membered pseudo sugar 2‐phospholene ring are mentioned, and the oxidation is examined on several substituted 2‐phospholenes (1a–i). © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:320–325, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10154
3‐Aryl‐5‐furylpyrazolines and their biological activities
Authors: Cetin A. , Cansiz A. , Digrak M.
Published: May 2003

Aryl‐furyl substituted pyrazolines 2a–c and 4a–c were prepared by the reaction of α,β‐unsaturated carbonyl compounds with hydrazine or phenyl hydrazine. N‐chloroacetyl derivatives 3a–c were obtained by the N‐acetylation of 2a–c. The antibacterial activities of synthesized pyrazolines were examined by employing the disk‐diffusion technique. All synthesized compounds showed antibacterial effects in 1200 μg concentration. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:345–347, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10159
Reactivity of diacyloxyiodobenzenes toward trivalent phosphorus nucleophiles
Authors: Makowiec Sławomir , Rachon Janusz
Published: May 2003

The reaction of diacyloxyiodobenzenes and tetravalent phosphorus nucleophiles was investigated. It was established that both H‐phosphonates and secondary phosphine oxides react with diacetoxyiodobenzene in alcohols in the presence of sodium alcoholates yielding trialkyl phosphates and alkyl phosphinates respectively. For this transformation reactive intermediate 6 is proposed. In contrast to this, the treatment of diacetoxyiodobenzene with 3 equiv of sodium diisopropyl phosphite in THF produces diisopropyl 1‐(diisopropoxyphosphinyl)ethylphosphonate with excellent yield. It was found that diacyloxyiodobenzene/PR3 system may serve as an acylating agent; the acylation process can proceed via carboxylic acid anhydride or acylphosphonium salt 17 depending on the protocol used. New very efficient method for synthesis of 2,4,6‐trimethylbenzoic anhydride was developed. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:352–359, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10161
2,2″‐Dimethoxy‐1,1′:3′,1″‐terphenyl as a novel protective group for low‐coordinated phosphorus compounds: The case of diphosphenes
Authors: Ionkin Alex S. , Marshall William J.
Published: May 2003

A synthetic approach to meta‐terphenyls iodides bearing methoxy groups in the 2 and 2′′′ positions has been described. 2,2″‐Dimethoxy‐1,1′:3′,1″‐terphenyl groups have been shown to stabilize diphosphenes in solution. The existence of conformers of the diphosphene 7 has also been recorded. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:360–360, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10162
Synthesis of tert‐butylcalix[4]arenes modified with germanium‐containing side‐chains at the lower rim
Authors: Sakurai Takayuki , Takeuchi Yoshito
Published: May 2003

Bis‐, tris‐, and tetrakis‐trimethylgermylpropanoyl esters of p‐tert‐butylcalix[4]arenes 5, 7, and 8 were synthesized and their conformations in solution were determined by 1H and 13C NMR spectroscopy. The characteristic pair of doublets from the ArCH2Ar methylene protons was observed, indicating that all the prepared calixarenes were in the cone conformation. These germylated calixarenes failed to exhibit any appreciable cation‐capturing ability, indicating that further modification is required to make these compounds to be effective ditopic hosts. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:365–373, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10164
Biphasic role of TGF‐β1 in signal transduction and crosstalk
Authors: Wenner Charles E. , Yan Shaochun
Published: May 2003

TGF‐β1 induces cell cycle activation in mouse embryonic fibroblasts by down regulation of p27Kip1 but it can also induce delay of EGF‐induced cell cycle activation in these cells under similar conditions. In an attempt to determine the basis for these responses, the study of early TGF‐β1‐induced signal transduction pathways in the presence and absence of EGF was undertaken. It is proposed that a likely target for the inhibition by TGF‐β1 of the early EGF‐induced p42/p44 MAPK is at the c‐Raf locus. The finding that the catalytic subunits of PKA are associated with Raf‐1 within minutes following application of TGF‐β1 but not EGF in fibroblasts arrested in early G1 is suggestive of a role of PKA‐Raf‐1 interaction in TGF‐β1 induced delay of EGF‐induced cell cycle kinetics. A model for TGF‐β1 induced translocation to the plasma membrane‐associated Raf‐1 is proposed. Reports that Rho‐like GTPase activity is critical for the activation of TGF‐β1 downstream pathways raises the question as to whether Rho proteins are involved in these observed TGF‐β1‐induced responses. Post‐receptor signaling mechanisms for TGF‐β1 and cross‐talk with PKA‐mediated pathways are examined in an effort to explain the modulation by TGF‐β1 of mitogen‐induced cell proliferation in mesenchymal cells. © 2003 Wiley‐Liss, Inc.
Overcoming resistance of cancer cells to apoptosis
Authors: Hersey Peter , Zhang Xu Dong
Published: May 2003

Discovery of the B cell lymphoma gene 2 (Bcl‐2 gene) led to the concept that development of cancers required the simultaneous acquisition, not only of deregulated cell division, but also of resistance to programmed cell death or apoptosis. Apoptosis is arguably the common pathway to cell death resulting from a range of therapeutic initiatives, so that understanding the basis for the resistance of cancer cells to apoptosis may hold the key to development of new treatment initiatives. Much has already been learnt about the apoptotic pathways in cancer cells and proteins regulating these pathways. In most cells, apoptosis is dependent on the mitochondrial dependent pathway. This pathway is regulated by pro‐ and anti‐apoptotic members of the Bcl‐2 family, and manipulation of these proteins offers scope for a number of treatment initiatives. Effector caspases activated by the mitochondrial pathway or from death receptor signaling are under the control of the inhibitor of apoptosis protein (IAP) family. Certain proteins from mitochondrial can, however, competitively inhibit their binding to effector caspases. Information about the structure of these proteins has led to initiatives to develop therapeutic agents to block the IAP family. In addition to development of selective agents based on these two (Bcl‐2 and IAP) protein families, much has been learnt about signal pathways that may regulate their activity. These in turn might provide additional approaches based on selective regulators of the signal pathways. © 2003 Wiley‐Liss, Inc.
BRCA1 gene in breast cancer
Authors: Rosen Eliot M. , Fan Saijun , Pestell Richard G. , Goldberg Itzhak D.
Published: May 2003

The BRCA1 gene was identified and cloned in 1994 based its linkage to early onset breast cancer and breast‐ovarian cancer syndromes in women. While inherited mutations of BRCA1 are responsible for about 40–45% of hereditary breast cancers, these mutations account for only 2‐3% of all breast cancers, since the BRCA1 gene is rarely mutated in sporadic breast cancers. However, BRCA1 expression is frequently reduced or absent in sporadic cancers, suggesting a much wider role in mammary carcinogenesis. Since BRCA1 was cloned in 1994, its molecular function has been the subject of intense investigation. These studies have revealed multiple functions of the BRCA1 that may contribute to its tumor suppressor activity, including roles in: cell cycle progression, several highly specialized DNA repair processes, DNA damage‐responsive cell cycle checkpoints, regulation of a set of specific transcriptional pathways, and apoptosis. Many of these functions are linked to protein:protein interactions involving different portions of the 1,863 amino acid (aa) BRCA1 protein. BRCA1 functions in cell cycle progression and the DNA damage response appear to be regulated by distinct and specific phosphorylation events, but the molecular pathways activated by these phosphorylations are only beginning to be unraveled. In addition, the reason that BRCA1 mutation carriers develop specific tumor types (breast and ovarian cancers in women and possibly prostate cancers in men) is not clearly understood. Elucidation of the precise molecular functions of the BRCA1 gene product will greatly enhance our understanding of the pathogenesis of hereditary as well as sporadic mammary carcinogenesis. © 2003 Wiley‐Liss, Inc.
Effect of high phosphate concentration on osteoclast differentiation as well as bone‐resorbing activity
Authors: Kanatani Masanori , Sugimoto Toshitsugu , Kano Junichi , Kanzawa Michiko , Chihara Kazuo
Published: May 2003

Although high inorganic phosphate (Pi) concentration in culture media directly inhibits generation of new osteoclasts and also inhibits bone resorption by mature osteoclasts, its precise mechanism and the physiological role have not been elucidated. The present study was performed to investigate these issues. Increase in extracellular Pi concentration ([Pi]e) (2.5–4 mM) concentration dependently inhibited 1,25‐dihydroxyvitamin D3 [1,25(OH)2D3] or parathyroid hormone (PTH)‐(1‐34)‐induced osteoclast‐like cell formation from unfractionated bone cells in the presence of stromal cells. Increase in [Pi]e (2.5–4 mM) concentration dependently inhibited 1,25(OH)2D3‐, PTH‐(1‐34)‐, or receptor activator of NF‐κB ligand (RANKL) and macrophage colony‐stimulating factor (M‐CSF)‐induced osteoclast‐like cell formation from hemopoietic blast cells in the absence of stromal cells. Increase in [Pi]e (2.5–4 mM) dose dependently stimulated the expression of osteoprotegerin (OPG) mRNA and increased the expression of OPG mRNA suppressed by PTH‐(1‐34) or 1,25(OH)2D3 in unfractionated bone cells, while it did not affect RANKL mRNA. Increase in [Pi]e (2.5‐4 mM) concentration dependently inhibited the bone‐resorbing activity of isolated rabbit osteoclasts. Increase in [Pi]e (4 mM) induced the apoptosis of isolated rabbit osteoclasts while it did not affect the apoptosis of osteoclast precursor cells and mouse macrophage‐like cell line C7 cells that can differentiate into osteoclasts in the presence of RANKL and M‐CSF. These results indicate that increase in [Pi]e inhibits osteoclast differentiation both by up‐regulating OPG expression and by direct action on osteoclast precursor cells. It is also indicated that increase in [Pi]e inhibits osteoclastic activity at least in part by the direct induction of apoptosis of osteoclasts. © 2003 Wiley‐Liss, Inc.
Adhesion‐dependent control of Akt/protein kinase B occurs at multiple levels
Authors: Le Gall Maude , Chambard Jean‐Claude , Grall Dominique , Van Obberghen‐Schilling Ellen
Published: May 2003

The protein kinase Akt, also known as Protein Kinase B, has been implicated in the survival of several cell types challenged with various apoptotic stimuli. In CCL39 lung fibroblasts, apoptosis is induced by anchorage and mitogen removal. Mitogen‐induced activation of Akt is highly anchorage dependent in these cells and removal of adhesion is accompanied by a rapid loss in responsiveness to soluble agonists followed by a significant decrease in Akt abundance. Loss of the protein appears to be independent of kinase activation since the expression of a constitutively active form, gag‐Akt, is also dependent upon cell adhesion. Although the disappearance of Akt is coincident with the induction of programmed cell death, it cannot be fully prevented by treatment of cells with the caspase inhibitor ZVAD or by sustained activation of the anti‐apoptotic Raf/ERK pathway, in cells expressing an inducible ΔRaf‐1:ER construct. In addition, a previously unrecognized decrease in Akt mRNA levels following anchorage removal occurs suggesting that anchorage‐dependent transcriptional and/or post‐transcriptional mechanisms contribute to the adhesion‐dependent regulation of Akt expression. © 2003 Wiley‐Liss, Inc.
Transgenic mice with dominant negative PKC‐theta in skeletal muscle: A new model of insulin resistance and obesity
Authors: Serra C. , Federici M. , Buongiorno A. , Senni M.I. , Morelli S. , Segratella E. , Pascuccio M. , Tiveron C. , Mattei E. , Tatangelo L. , Lauro R. , Molinaro M. , Giaccari A. , Bouché Marina
Published: May 2003

Protein kinase C θ (PKC‐θ) is the PKC isoform predominantly expressed in skeletal muscle, and it is supposed to mediate many signals necessary for muscle histogenesis and homeostasis, such as TGFβ, nerve‐dependent signals and insulin. To study the role of PKC‐θ in these mechanisms we generated transgenic mice expressing a “kinase dead” mutant form of PKC‐θ (PKC‐θK/R), working as “dominant negative,” specifically in skeletal muscle. These mice are viable and fertile, however, by the 6–7 months of age, they gain weight, mainly due to visceral fat deposition. Before the onset of obesity (4 months of age), they already show increased fasting and fed insulin levels and reduced insulin‐sensitivity, as measured by ipITT, but normal glucose tolerance, as measured by ipGTT. After the 6–7 months of age, transgenic mice develop hyperinsulinemia in the fasting and fed state. The ipGTT revealed in the transgenic mice both hyperglycemia and hyperinsulinemia. At the molecular level, impaired activation of the IR/IRS/PI3K pathway and a significant decrease both in the levels and in insulin‐stimulated activation of the serine/threonine kinase Akt were observed. Taken together these data demonstrate that over‐expression of dominant negative PKC‐θ in skeletal muscle causes obesity associated to insulin resistance, as demonstrated by defective receptor and post‐receptorial activation of signaling cascade. © 2003 Wiley‐Liss, Inc.
Threonine 308 phosphorylated form of akt translocates to the nucleus of PC12 cells under nerve growth factor stimulation and associates with the nuclear matrix protein nucleolin
Authors: Borgatti Paola , Martelli Alberto M. , Tabellini Giovanna , Bellacosa Alfonso , Capitani Silvano , Neri Luca M.
Published: May 2003

We have examined the issue of whether or not in PC12 cells it may be observed a nerve growth factor (NGF) nuclear translocation of an active (phosphorylated) Akt. Western blot analysis with antibodies to either total or phosphorylated Akt showed a maximal nuclear translocation after 15 min of NGF stimulation. NGF increased rapidly and transiently the enzymatic activity of immunoprecipitable nuclear Akt and after 45 min the values returned to a level close to the basal one. Enzyme translocation was blocked by the selective phosphoinositide 3‐kinase inhibitor, LY294002. Confocal microscopy of samples stained with antibody to Akt showed an evident increase in immunostaining intensity in the nuclear interior after NGF treatment. Treatment of cells with inhibitors of protein phosphatase PP2A, calyculin A, or okadaic acid, maintained the phosphorylation levels of nuclear Akt. Immunoprecipitation experiments revealed an association between Akt and PP2A that was maximal when nuclear Akt activity was decreased. Both total and active Akt associated with the nuclear matrix and, in particular, with the protein nucleolin, with which Akt co‐immunoprecipitated. These findings strongly suggest that the intranuclear translocation of active Akt is an important step in the signaling pathways elicited by the neurotrophin NGF and that the intranuclear control of Akt is achieved through the action of PP2A. © 2003 Wiley‐Liss, Inc.
Thrombin downregulates muscle acetylcholine receptors via an IP3 signaling pathway by activating its G‐protein‐coupled protease‐activated receptor‐1
Authors: Faraut Brice , Barbier Julien , Ravel‐Chapuis Aymeric , Doyennette Marie‐Agnès , Jandrot‐Perrus Martine , Verdière‐Sahuqué Martine , Schaeffer Laurent , Koenig Jeanine , Hantaï Daniel
Published: May 2003

Regulation of thrombin activity may be required during skeletal muscle differentiation since the thrombin tissue inhibitor protease nexin‐1 appears at the myotube stage before being localized at the neuromuscular synapse. Here, we have used a model of rat fetal myotube primary cultures to study the effect of thrombin on acetylcholine receptor (AChR) expression, which is enhanced at the myotube stage. Our results show that thrombin decreases both the number of surface AChRs (AChRn) and AChR α‐subunit gene expression. Using the agonist peptide SFLLRN, we establish that the AChRn decrease is mediated by the G protein‐coupled thrombin receptor “protease‐activated receptor‐1” (PAR‐1). Moreover, the specific thrombin inhibitor hirudin increases AChRn by inhibiting the thrombin intrinsically present in the cultures. We further demonstrate that the activation of PAR‐1 by thrombin induces intracellular calcium movements that are blocked by 2‐APB, an inhibitor of inositol 1,4,5‐triphosphate (IP3)‐induced calcium release. These calcium signals are more intense in nuclei than in the cytoplasm and are consistent with the intracellular distribution of IP3 receptor that we find in the cytoplasm in a cross‐striated pattern and at a high level in the nuclear envelope zone. Finally, we show that the blockade of these IP3‐induced calcium signals by 2‐APB prevents the AChRn decrease induced by thrombin. Our results thus demonstrate that thrombin downregulates AChR expression by activating PAR‐1 and that this effect is mediated via an IP3 signaling pathway. © 2003 Wiley‐Liss, Inc.
Primary culture model of peroxisome proliferator‐activated receptor γ activity in prostate cancer cells
Authors: Xu Yue , Iyengar Sunita , Roberts Richard L. , Shappell Scott B. , Peehl Donna M.
Published: May 2003

BRL 49653 (rosiglitazone) is a thiazolidinedione anti‐diabetic drug that activates the nuclear receptor, peroxisome proliferator‐activated receptor gamma (PPARγ). Pilot clinical trials have shown evidence of therapeutic activity of PPARγ agonists against prostate cancer. To more effectively use PPARγ ligands to treat this common and generally chemo‐resistant type of cancer, it will be necessary to better understand the nature of PPARγ activity in prostate cancer cells. Tumor suppressor effects of activation of PPARγ may include suppression of growth and/or induction of differentiation or apoptosis. We investigated responses of primary cultures of human prostatic cancer cells to BRL 49653. PPARγ was expressed in all of the cell strains examined. BRL 49653 caused dose‐ and time‐dependent growth inhibition that was associated with increased expression of the transcription repressor, transforming growth factor β‐stimulated clone 22 (TSC‐22), and markedly increased expression of the secretory differentiation‐associated gene adipophilin. Adipocyte‐type fatty acid binding protein (aFABP), neutrophil gelatinase‐associated lipocalin (NGAL), glycerol kinase (GyK), and β‐catenin, which are regulated by PPARγ ligands in certain other types of cells, were not regulated by BRL 49653 in prostate cells. Upregulation of adipophilin coincided with morphological changes and the appearance of cytoplasmic vacuoles with ultrastructural features of secondary lysosomes. These results extend previous studies with established cancer cell lines and show that PPARγ agonists can inhibit proliferation and modulate expression of secretory‐associated genes in primary cultures of prostate cancer cells, further warranting consideration of these agents as pro‐differentiating chemotherapeutic or chemoprevention agents for the treatment of prostate cancer. © 2003 Wiley‐Liss, Inc.