bluuebunny/crossref_metadata_2025 huggingface dataset:
Diadenosine polyphosphates as extracellular signal molecules
Authors: Hoyle Charles H.V. , Hilderman Richard H. , Pintor Jesús J. , Schlüter Hartmut , King Brian F.
Published: August 2002

Dinucleoside polyphosphates are an interesting group of signalling molecules that control numerous physiological functions. Diadenosine compounds, with a backbone of anything from two to seven phosphates, are known to occur naturally. Some of them have been isolated from cerebral nerve terminals and, acting via nucleoside (P1), nucleotide (P2), or dinucleotide receptors, can affect central nervous system function. Many of them have been isolated from human blood platelet secretory granules and are potentially involved in haemostatic mechanisms and peripheral control of vascular tone. Many visceral organs respond to the application of adenine dinucleotides and, although they act on receptors in the periphery that can be mainly defined as either P1 or P2, evidence is now accumulating for discrete dinucleotide receptors. In the periphery, adenine dinucleotides can be potent agonists, with diverse functions, causing contraction or relaxation of smooth muscle. Many P2X receptor proteins and P2Y receptors have been cloned and adenine dinucleotides have a variable pharmacological profile at these receptors and may be useful tools for characterising subtypes of P2X and P2Y receptors. This review provides a broad description of the many extracellular roles of diadenosine polyphosphates as emerging, yet increasingly important, natural ligands for a plethora of structurally diverse mononucleotide and dinucleotide receptors. Drug Dev. Res. 52:260–273, 2001. © 2001 Wiley‐Liss, Inc.
Pharmacological and endocrine characterization of A‐198401, an orally active GnRH antagonist, in intact and castrate male rat models
Authors: Besecke Leslie M. , Diaz Gilbert J. , Segreti Jason A. , Mohning Kurt M. , Cybulski Van A. , Rao Mira , Bush Eugene N. , Randolph John T. , Waid Philip L. , Haviv Fortuna , Wegner Craig D. , Greer Jonathan
Published: August 2002

Gonadotropin‐releasing hormone (GnRH) stimulates the synthesis and secretion of the gonadotropins that maintain the reproductive axis in mammals. Efforts have focused on the characterization of novel, nonpeptidic orally active antagonists of the GnRH receptor. An erythromycin A derivative, A‐198401 (11‐deoxy‐11‐[carboxy (3,4‐dichlorophenethyl) amino]‐3‐O‐[4‐(S)‐methyl‐oxazolidin‐2‐one] carbamoyl‐5‐O‐(3′‐N‐desmethyl‐3′‐N‐cyclopropylmethyl) desosaminyl‐6‐O‐methyl‐erythronolide A 11,12‐(cyclic carbamate), showed nanomolar affinity for the human (CHO‐21) and rat GnRH receptors in vitro (pK values 8.7 ± 0.2 and 9.2 ± 0.14, respectively). In a functional in vitro assay, A‐198401 inhibited leuprolide‐induced release of luteinizing hormone (LH) from cultured rat pituitary cells with a pA2 value of 8.8. Intravenous (IV) dosing of A‐198401 in castrate male rats produced a significant dose‐dependent suppression of LH production with an ED80 value of 5.26 mg/kg. Sustained testosterone (T) suppression was observed after IV dosing of A‐198401 in the intact rat, with a 10‐mg/kg‐dose producing 9–24 h suppression. Analysis of the IV and PO data indicate that A‐198401 has a bioavailability of 15%. A‐198401 is a novel nonpeptide GnRH antagonist that produces significant and sustained suppression of LH and T production in animal models when dosed either IV or PO and may provide the basis for a therapeutic GnRH antagonist for the clinical treatment of reproductive hormone‐dependent diseases. Drug Dev. Res. 52:485–491, 2001. © 2001 Wiley‐Liss, Inc.
Increase of learning abilities and maturation of the vertical lobe complex during postembryonic development in the cuttlefish, Sepia
Authors: Dickel Ludovic , Chichery Marie‐Paule , Chichery Raymond
Published: August 2002

When shown prawns in a glass tube, cuttlefish quickly learn to inhibit their predatory behavior. By using a visual learning paradigm, we studied training and retention performances of cuttlefish aged from 8 to 90 days. We found an improvement in the acquisition of learning abilities during the first 2 months of life as well as an increase of 24‐hr retention performance between 30 and 90 days of age. Using morphometric measurements of different lobes of the central nervous system, we correlated the emergence of these learning abilities with the postembryonic development of related nervous structures. Our results show that only the growth of the superior frontal and vertical lobes appears to be significantly correlated with the improvement of learning and long‐term retention performances. Thus, as found in earlier data collected in Octopus, the vertical lobe complex of the cuttlefish seems to be involved in these learning processes. © 2001 John Wiley & Sons, Inc. Dev Psychobiol 40: 92–98, 2001
Severe hypoglycaemia in patients with type 1 diabetes and impaired awareness of hypoglycaemia: a comparative study of insulin lispro and regular human insulin
Authors: Ferguson Stewart C. , Strachan Mark W. J. , Janes Jonathan M. , Frier Brian M.
Published: August 2002

Objective

To assess the potential of insulin lispro to limit the frequency of severe hypoglycaemia without compromising glycaemic control in a cohort of patients with type 1 diabetes who are at a high risk of severe hypoglycemia.

Research design and methods

An open‐label, randomised, 12‐month comparative crossover study of insulin lispro and regular human insulin was performed in 33 patients with type 1 diabetes with impaired hypoglycaemia awareness. The efficacy of each treatment was evaluated by glycaemic control (HbA1c), eight‐point home blood glucose profiles, and the frequency and severity of hypoglycaemic episodes and quality of life.

Results

Eighteen (55%) patients experienced one or more episodes of severe hypoglycaemia in the 48 weeks of study. There was a trend to a lower incidence of severe hypoglycaemia during treatment with insulin lispro in comparison with regular human insulin (55 vs 84 episodes, p=0.087). This resulted principally from a 47% lower incidence of nocturnal severe hypoglycaemia with insulin lispro (25 vs 47 episodes, p=0.11). The lower frequency of severe hypoglycaemia associated with insulin lispro was not explained by differences in glycated haemoglobin between insulin treatments (HbA1c 9.1% insulin lispro vs 9.3% regular human insulin).

Conclusions

In individuals with type 1 diabetes, who have impaired awareness of hypoglycaemia, treatment with insulin lispro may be associated with a lower incidence of severe hypoglycaemia manifested predominantly through less frequent nocturnal episodes. Insulin lispro may have a beneficial role in the management of patients with diabetes at risk of severe hypoglycaemia, although a larger study is required to confirm these findings. Copyright © 2001 John Wiley & Sons, Ltd.
Composition of LDL as determinant of its susceptibility to in vitro oxidation in patients with well‐controlled type 2 diabetes
Authors: Scheffer P. G. , Bakker S. J. L. , Popp‐Snijders C. , Heine R. J. , Schutgens R. B. H. , Teerlink T.
Published: August 2002

Background

There is increasing evidence that oxidation of low‐density lipoprotein (LDL) in the vascular wall plays an important role in the development of atherosclerosis. The present study was undertaken to characterise how different constituents of LDL contribute to its in vitro oxidisability.

Methods

The LDL composition, i.e. lipids, antioxidants, fatty acids, plasmenylcholines, and baseline level of conjugated dienes (CD) of 94 well‐controlled and normolipidaemic type 2 diabetic patients was measured. Two oxidisability indices were determined: the lag time, reflecting the resistance of LDL to copper‐induced oxidation, and the amount of conjugated dienes formed during oxidation of LDL.

Results

The lag time was not related to the total level of saturated, monounsaturated, and polyunsaturated fatty acids, but a strong inverse relationship was observed with fatty acids with three or more double bonds (r=−0.56, p<0.001). In addition, an inverse relation was observed between the lag time and LDL‐plasmenylcholine (r=−0.35, p<0.001). Although not related to lag time in univariate analysis, α‐tocopherol was a significant determinant in multiple regression analysis. A multiple linear regression model with LDL polyunsaturated fatty acids with three or more double bonds, α‐tocopherol, monounsaturated fatty acids, and plasmenylcholines as determinants explained 47% of the variation in lag time. CD production was negatively correlated to oleic acid and positively to linoleic acid (r=−0.45 and r=0.73, respectively; p<0.001).

Conclusions

Fatty acids with three or more double bonds were the most important predictor of LDL lag time, whereas oleic acid and linoleic acid were major determinants of the amount of CD formed during oxidation of LDL. Copyright © 2001 John Wiley & Sons, Ltd.
Type IIA procollagen: Expression in developing chicken limb cartilage and human osteoarthritic articular cartilage
Authors: Nah Hyun‐Duck , Swoboda Bernd , Birk David E. , Kirsch Thorsten
Published: August 2002

Type IIA procollagen is an alternatively spliced product of the type II collagen gene and uniquely contains the cysteine (cys)–rich globular domain in its amino (N)–propeptide. To understand the function of type IIA procollagen in cartilage development under normal and pathologic conditions, the detailed expression pattern of type IIA procollagen was determined in progressive stages of development in embryonic chicken limb cartilages (days 5–19) and in human adult articular cartilage. Utilizing the antibodies specific for the cys‐rich domain of the type IIA procollagen N‐propeptide, we localized type IIA procollagen in the pericellular and interterritorial matrix of condensing pre‐chondrogenic mesenchyme (day 5) and early cartilage (days 7–9). The intensity of immunostaining was gradually lost with cartilage development, and staining became restricted to the inner layer of perichondrium and the articular cap (day 12). Later in development, type IIA procollagen was re‐expressed at the onset of cartilage hypertrophy (day 19). Different from type X collagen, which is expressed throughout hypertrophic cartilage, type IIA procollagen expression was transient and restricted to the zone of early hypertrophy. Immunoelectron microscopic and immunoblot analyses showed that a significant amount of the type IIA procollagen N‐propeptide, but not the carboxyl (C)–propeptide, was retained in matrix collagen fibrils of embryonic limb cartilage. This suggests that the type IIA procollagen N‐propeptide plays previously unrecognized roles in fibrillogenesis and chondrogenesis. We did not detect type IIA procollagen in healthy human adult articular cartilage. Expression of type IIA procollagen, together with that of type X collagen, was activated by articular chondrocytes in the upper zone of moderately and severely affected human osteoarthritic cartilage, suggesting that articular chondrocytes, which normally maintain a stable phenotype, undergo hypertrophic changes in osteoarthritic cartilage. Based on our data, we propose that type IIA procollagen plays a significant role in chondrocyte differentiation and hypertrophy during normal cartilage development as well as in the pathogenesis of osteoarthritis. © 2001 Wiley‐Liss, Inc.
Flanking regulatory sequences of the locus encoding the murine GDNF receptor, c‐ret, directs lac Z (β‐galactosidase) expression in developing somatosensory system
Authors: Sukumaran Madhu , Waxman Stephen G. , Wood John N. , Pachnis Vassilis
Published: August 2002

RET forms the catalytic component within the receptor complex that transmits signals from the GDNF family of neurotrophic factors. To study the mechanisms regulating the cell‐type specific expression of this gene, we have cloned and characterised the murine c‐ret locus. A cosmid contig comprising approximately 60 kb of the mouse genome encompassing the entire structural gene and flanking sequences have been isolated and the transcription initiation site identified and promoter characterised. The murine c‐ret promoter lacks a TATA initiation motif and has GC enriched DNA sequences reminiscent of CpG islands. Analysis of transgenic mice lines bearing the Lac Z (β‐galactosidase) reporter gene under the control of 5′ flanking sequences show modularity in the organisation of cis‐regulatory domains within the locus. Cloned 5′ flanking sequences comprise a distal regulatory domain directing Lac Z expression at the primitive streak, lateral mesoderm and facial ganglia and a proximal sensory neurones specific regulatory domain inducing Lac Z expression primarily within the developing somatosensory system. The spatial and temporal progression of transgene expression precisely recapitulates endogenous gene expression in developing sensory ganglia including its induction in postnatal Isolectin B4 binding nociceptive neurones. © 2001 Wiley‐Liss, Inc.
The Anorexia Nervosa Stages of Change Questionnaire (ANSOCQ): Information regarding its psychometric properties
Authors: Rieger Elizabeth , Touyz Stephen W. , Beumont Peter J. V.
Published: August 2002

Objective

The Anorexia Nervosa Stages of Change Questionnaire (ANSOCQ) was developed to assess patients' readiness to recover from anorexia nervosa. In this article we present additional findings supporting the psychometric properties of the ANSOCQ.

Method

Forty‐four inpatients with anorexia nervosa participated in the study. At the time of admission, patients were requested to complete the ANSOCQ as well as several other self‐report questionnaires assessing constructs related to readiness to change.

Results

The ANSOCQ demonstrated good construct‐related validity in that significant correlations emerged between the ANSOCQ and instruments assessing the theoretically related constructs of decisional balance and self‐efficacy.

Discussion

Having developed a reliable and valid self‐report questionnaire for the assessment of readiness to change in anorexia nervosa, the ANSOCQ provides a means of addressing motivational hypotheses which have been advanced in the context of eating disorders. © 2002 by Wiley Periodicals, Inc. Int J Eat Disord 32: 24–38, 2002.
Urine electrolytes as markers of bulimia nervosa
Authors: Crow Scott J. , Rosenberg Mark E. , Mitchell James E. , Thuras Paul
Published: August 2002

Objective

The diagnosis of bulimia nervosa (BN) is often delayed because patients are frequently secretive about the illness. Prior work has examined several potential diagnostic markers, none of which has been both highly sensitive and specific. Little is known about the utility of urine electrolytes in detecting BN symptoms.

Method

Seventy‐seven women with BN and 53 control women participated in the study. Urine and serum electrolytes and urine phenolthalein screens were obtained. Subjects with BN also completed a self‐report instrument (the Eating Behaviors IV) regarding vomiting during the week prior to assessment. Receiver operating characteristic analysis was used to examine the predictive abilities of urine and serum electrolytes.

Results

Bulimic and control subjects differed significantly on most electrolyte measures. The ratio of urine sodium to urine chloride was the best predictor of bulimic behavior; selecting individuals with a ratio of >1.16 identified 51.5% of BN subjects with a 5% false‐positive rate. Fractional excretion of sodium (FENA), urine anion gap (UAG), and serum potassium values were also predictive of BN but serum hypokalemia was not more common in BN than in control subjects (4.1% vs. 0%; p = .15). Vomiting frequency was correlated with an abnormal UAG (r2 = .2231) but not FENA, nor serum potassium.

Conclusion

The ratio of urine sodium to urine chloride is a useful predictor of bulimic behavior that appears to be more powerful in detecting BN than traditional screening measures such as serum hypokalemia. © 2001 by John Wiley & Sons, Inc. Int J Eat Disord 30: 279–287, 2001.
The growth rate of Trivelpiece–Gould modes excited in a beam–plasma system
Authors: Morimoto Toshifumi , Mori Ichiro
Published: August 2002

When an electron beam is injected into a low‐pressure gas (about 10−4 Torr), various waves are produced by the beam–plasma interactions. These waves are expressed by Trivelpiece–Gould modes that consider the boundary conditions. The growth rate has almost never been sought until now. In this paper, we explain which modes are strongly excited when the gas pressure is changed in a beam–plasma system based on the results of improving the linear dispersion relation used by Trivelpiece and Gould and performing the calculations in complex numbers. The properties of the waves found by this calculation are compared with our experimental results. © 2001 Scripta Technica, Electron Comm Jpn Pt 2, 84(4): 9–15, 2001
Parallel processing of steady‐state analysis for a power electronic system by PVM3
Authors: Kato Toshiji , Minato Hirotaka
Published: August 2002

It is important to get a steady‐state operation of a power electronic circuit for its design. The shooting method, which is one of the steady‐state analysis methods, solves a boundary value condition which equates initial values to final values after one‐period transient. This paper proposes how to process the analysis in parallel by using a Parallel Virtual Machine (PVM3) system. In particular, the multiple shooting method (MSM) which divides the shooting time into subsections is suitable because it can parallel numerical processes for the divided shooting times by using multiple CPU units independently. This parallel method is applied to converter examples which are processes by PVM3. The computed results are investigated for their convergence and CPU times to check their parallel effects. According to the MSM algorithm, CPU times are reduced almost to one‐fifth by using five computer units from a PVM3 system example. © 2001 Scripta Technica, Electr Eng Jpn, 135(2): 69–76, 2001
Characterization of mutant spectra generated by a forward mutational assay for gene A of ΦX174 from ENU‐treated transgenic mouse embryonic cell line PX‐2†
Authors: Valentine Carrie R. , Montgomery Beverly A. , Miller Scott G. , Delongchamp Robert R. , Fane Bentley A. , Malling Heinrich V.
Published: August 2002

The sensitivity of in vivo transgenic mutation assays benefits from the sequencing of mutations, although the large number of possible mutations hinders high throughput sequencing. A forward mutational assay exists for ΦX174 that requires an altered, functional ΦX174 protein and therefore should have fewer targets (sense, base‐pair substitutions) than forward assays that inactivate a protein. We investigated this assay to determine the number of targets and their suitability for detecting a known mutagen, N‐ethyl‐N‐nitrosourea (ENU). We identified 25 target sites and 33 different mutations in ΦX174 gene A after sequencing over 350 spontaneous and ENU‐induced mutants, mostly from mouse embryonic cell line PX‐2 isolated from mice transgenic for ΦX174 am3, cs70 (line 54). All six types of base‐pair substitution were represented among both the spontaneous and ENU‐treated mutant spectra. The mutant spectra from cells treated with 200 and 400 μg/ml ENU were both highly different from the spontaneous spectrum (P < 0.000001) but not from each other. The dose trend was significant (P < 0.0001) for a linear regression of mutant frequencies (R2 = 0.79), with a ninefold increase in mutant frequency at the 400 μg/ml dose. The spontaneous mutant frequency was 1.9 × 10−5 and the spontaneous spectrum occurred at 11 target base pairs with 15 different mutations. Thirteen mutations at 12 targets were identified only from ENU‐treated cells. Seven mutations had highly significant increases with ENU treatment (P < 0.0001) and 15 showed significant increases. The results suggest that the ΦX174 forward assay might be developed into a sensitive, inexpensive in vivo mutagenicity assay. Environ. Mol. Mutagen. 39:55–68, 2002 Published 2002 Wiley‐Liss, Inc.
Spontaneous mutation of the lacI transgene in rodents: Absence of species, strain, and insertion‐site influence
Authors: Zhang Shulin , Glickman Barry W. , de Boer Johan G.
Published: August 2002

Comparison of spontaneous mutation spectra derived from different transgenic constructs can provide valuable insights for interpreting the mechanisms of spontaneous mutation. In this study, spontaneous mutation frequencies and spectra of the lacI transgene are compared in the liver of C57BL/6, B6C3F1, and BC‐1 mice and F344 rats. Before correction for clonal expansion, the mutant frequency varied from 2.6 ± 0.45 to 5.0 ± 2.4 × 10−5. Correction for potential clonal expansion reduced the range in mutation frequency to between 2.3 ± 0.45 and 3.5 ± 2.0 × 10−5. There is thus no statistical difference in spontaneous mutation frequency between the different strains and species. G:C → A:T transitions and to a lesser extent, G:C → T:A transversions dominate the mutational spectra in all of these animals. In three strains of mice, G:C → A:T transitions account for 50.7–53.3% of mutation, 81.7–83.8% of which involve CpG sites, whereas G:C → T:A transversions account for 17.8–32.9% of mutations with 43.2–50.0% found at CpG sites. In rats, G:C → A:T transitions account for 38.0% of the spectra, 70.0% of which involve CpG sites, whereas G:C → T:A transversions account for 23.0% of the spectra, 70.0% of which involve CpG sites. The distribution of other classes of mutations is also very similar. We conclude that, despite reports about species and strain differences in induced mutation, spontaneous mutations in the lacI transgene appear to be similar, regardless of genomic location, rodent strain, or species. In addition to insights into spontaneous mutation, this study also provides essential data for comparison with and interpretation of induced mutations. Environ. Mol. Mutagen. 37:141–146, 2001 © 2001 Wiley‐Liss, Inc.
Transfection of nonmelanocytic cells with tyrosinase gene constructs for survival studies
Authors: Kaur Jaskiran , Hill Helene Z.
Published: August 2002

To better understand the role of melanin in the response of cells to radiation, the vector pcTYR containing the tyrosinase cDNA and a control vector pcTYW with no tyrosinase cDNA were transfected and expressed in nonpigmented CHOK1‐AL 1282B5 cells. A pigmented clone was selected from the pcTYR transfectants and an antibiotic‐resistant clone was selected from the controls. Melanin was assessed qualitatively by electron paramagnetic resonance (EPR) and quantitatively by a 14C‐based assay. The EPR signal detectable in pcTYR‐containing cells was at least twice that of pcTYW and parental CHOK1‐AL cells and the tyrosinase activity was found to be at least six times greater. Melanin was classified to be eumelanin. Survivals of the transfectants were compared to those of the parent cells after irradiation by UVC from a germicidal lamp, UVB from TL01 lamps, UVA from Alisun lamps, UVB/UVA from FS20 lamps, and by γ‐rays from a 137Cs source. Compared to the pcTYW‐containing cells, the pigmented cells were more sensitive to killing by UVC, and resistant to killing by UVA and γ‐rays. There were no significant differences in survival after the other irradiations. These results suggest that the pigment synthesized by the activity of tyrosinase alone, unmodified by the activities of TRP1 and TRP2, is protective against the types of reactive oxygen species produced by UVA and γ‐rays but not protective against lethal damage from photons in the UVB range and sensitizes to UVC photons. Environ. Mol. Mutagen. 38:216–222, 2001 © 2001 Wiley‐Liss, Inc.
DNA repair and mutagenesis in Werner syndrome
Authors: Bohr Vilhelm A. , Souza Pinto Nadja , Nyaga Simon G. , Dianov Grigory , Kraemer Kenneth , Seidman Michael M. , Brosh Robert M.
Published: August 2002

Werner syndrome (WS) is the hallmark premature aging syndrome in which the patients appear much older than their actual chronological age. The disorder is associated with significantly increased genome instability and with transcriptional deficiencies. There has been some uncertainty about whether WS cells are defective in DNA repair. We thus examined repair in vitro in nuclear and mitochondrial DNA. Whereas cellular studies so far do not show significant DNA repair deficiencies, biochemical studies with the Werner protein clearly indicate that it plays a role in DNA repair. Environ. Mol. Mutagen. 38:227–234, 2001. Published 2001 Wiley‐Liss, Inc.
Targeting environmental improvements through ecological triage
Authors: Holt Diane , Viney Howard
Published: August 2002

This paper proposes a conceptualization of the approaches taken to determine whether, and which, companies should be targeted for improvement in their environmental performance and sustainability. Based on the concept of triage the paper proposes two approaches that the present authors argue could be utilized to select which companies should be forced or assisted into improving their environmental performance. The paper has four parts. It begins by outlining the authors' perceptions of the differences between a sustainable firm and environmental management. Secondly the authors examine the concept of triage, as used in disaster or battlefield conditions, and its applicability to greening businesses. Thirdly the authors propose two distinct triage scenarios that can be applied to selectively target businesses for environmental improvement or positive discrimination. Finally, the paper concludes by examining the possibility of selective targeting of businesses to green industry. Copyright © 2001 John Wiley & Sons, Ltd. and ERP Environment
Assessment of the production and economic risks of site‐specific liming using geostatistical uncertainty modelling
Authors: Rossel R. A. Viscarra , Goovaerts P. , McBratney A. B.
Published: August 2002

Precision agriculture (PA) offers the potential to improve the efficiency and environmental impact of conventional crop production systems. However, its implementation will depend on perceptions of how the adoption of technology will increase their yields and profit, and lower their production risk. This article presents an approach to help with this type of decision making. In this instance the consequences of three management scenarios (no lime, single‐rate liming and site‐specific lime applications to acidic field soil) were assessed in terms of production and economic risks. The methodology involved modelling the uncertainty about wheat yield, accounting for the local uncertainties about soil pH and lime requirement, and the uncertainties about crop model parameters used in the simulations. Indicator kriging (IK) was used together with Latin hypercube sampling (LHS) of the probability distributions of variables and model parameters for the propagation of uncertainties through to the output yield and net profit maps. These maps, together with a sensitivity analysis, were used to aid with decision making. Comparison of the three scenarios showed that, under the economic conditions of the analysis, the optimum was reached for a single‐rate application of 3.5 Mg/ha over the entire field instead of site‐specific lime applications. Copyright © 2001 John Wiley & Sons, Ltd.
Wind speed prediction in a complex terrain
Authors: Denison D. G. T. , Dellaportas P. , Mallick B. K.
Published: August 2002

We present a novel method for analysing spatial data when response data is given at a finite number of locations and the aim is to predict the response at a new location, where only a short run of data is available. This is the type of dataset that is typically available when attempting to analyse wind velocity data. We demonstrate our method, and compare it to that introduced by Haslett and Raftery on a set of data collected from the island of Crete in Greece. Typically the distance between locations is used to define the correlation matrix between responses at distinct locations even though this cannot always be justified. The peculiarity presented in our data is that the sites are in a complex topography so differences in the local characteristics of the wind station the direction of the prevailing winds, and other unobserved covariates can all lead to unsuitable model fitting. We use a nonlinear model to avoid these problems and demonstrate its predictive power in relation to the dataset under study. Copyright © 2001 John Wiley & Sons, Ltd.
A displacement‐based seismic design procedure for RC buildings and comparison with EC8
Authors: Panagiotakos T. B. , Fardis M. N.
Published: August 2002

A procedure for displacement‐based seismic design (DBD) of reinforced concrete buildings is described and applied to a 4‐storey test structure. The essential elements of the design procedure are: (a) proportioning of members for gravity loads; (b) estimation of peak inelastic member deformation demands in the so‐designed structure due to the design (‘life‐safety’) earthquake; (c) revision of reinforcement and final detailing of members to meet these inelastic deformation demands; (d) capacity design of members and joints in shear. Additional but non‐essential steps between (a) and (b) are: (i) proportioning of members for the ULS against lateral loads, such as wind or a serviceability (‘immediate occupancy’) earthquake; and (ii) capacity design of columns in flexure at joints. Inelastic deformation demands in step (b) are estimated from an elastic analysis using secant‐to‐yield member stiffnesses. Empirical expressions for the deformation capacity of RC elements are used for the final proportioning of elements to meet the inelastic deformation demands. The procedure is applied to one side of a 4‐storey test structure that includes a coupled wall and a two‐bay frame. The other side is designed and detailed according to Eurocode 8. Major differences result in the reinforcement of the two sides, with significant savings on the DBD‐side. Pre‐test calculations show no major difference in the seismic performance of the two sides of the test structure. Copyright © 2001 John Wiley & Sons, Ltd.
Seismic behaviour of multistorey RC wall–frame system versus bare ductile frame system
Authors: Lu Yong
Published: August 2002

The wall–frame systems have many known advantages, namely increase of the system's lateral strength and stiffness thereby allowing for a good tangential inter‐storey drift control, and the retention of a satisfactory energy dissipation capacity. However, rocking of the wall could occur as a result of uplifting wall base or concentrated plastic hinge deformations. Problems arising from this phenomenon have significant impact on the system behaviour and hence require extended study. This paper focuses on the wall‐rocking phenomenon due to the concentrated plastic hinge rotation at the wall base. To facilitate a comprehensive evaluation, a six‐storey three‐bay RC wall–frame structure is investigated with comparison to a bare ductile frame by means of earthquake simulation tests. The results revealed that, despite a superior performance over the ductile frame under low to moderate seismic actions, the wall–frame structure deteriorated more rapidly than the bare frame during advanced inelastic response. The increasingly significant rocking of the wall resulted in severe material damage at localized critical regions. Mitigating the wall rocking is seen to be a key to the further improvement of the system performance, and the extent to which this may be achieved by incorporating the three‐dimensional effects is explicitly illustrated by an analytical evaluation. Copyright © 2001 John Wiley & Sons, Ltd.
Eating disorders as manifestations of developmental disorders: language and the capacity for abstract thinking in psychotherapy of eating disorders
Authors: Buhl Charlotte
Published: August 2002

The serious eating disorders are manifestations of personality disorders which are characterized by an inadequately developed ability to distinguish and understand emotional states and needs. This paper focus on the development of transitional objects and an inner language as prerequisites for the ability to use words and abstract symbols as soothing and controlling functions. The psychotherapy of patients with eating disorders, and psychosomatic disorders, should be founded on the understanding of their concrete mode of functioning. It is important to avoid misunderstanding and interpreting both the symptoms and the patients' concretistic language as metaphors and symbols of their emotions and needs, before the development of an internal, meaningful language. This is essential for a successful psychotherapeutic result. Copyright © 2001 John Wiley & Sons, Ltd and Eating Disorders Association.
The essential oil co‐distillation by superheated vapour of organic solvents from aromatic plants
Authors: Mastelić Josip
Published: August 2002

A method of essential oil co‐distillation by superheated vapour of solvents was developed and the apparatus was presented. As suitable solvents, pentane and ether (inert solvent with low boiling point) were used. The method was tested on sage, Salvia officinalis L., as an aromatic plant. The essential oil of this plant was also isolated by hydrodistillation as a standard method. The isolated volatiles obtained by two methods were analysed using gas chromatography (GC) and gas chromatography–mass spectrometry (GC–MS). The obtained results were compared. This method of distillation enables safe isolation of monoterpene and sesquiterpene compounds, as well as hydrodistillation. Copyright © 2001 John Wiley & Sons, Ltd.
Essential oil composition of the aerial parts of Cachrys sicula L.
Authors: Palá‐Paúl Jesús , Velasco‐Negueruela Arturo , Pérez‐Alonso M. José , Sanz Jesús
Published: August 2002

The oil constituents from the aerial parts of Cachrys sicula L., gathered in different locations of Spain, have been studied by GC and GC–MS. We have analysed the oil from the fruits, flowers, stems and leaves, and umbels' rays. The major constituents in the different oils analysed were found to be p‐cymene (7.3–36.7%), γ‐terpinene (1.8–27.2%), α‐pinene (3.9–21.8%), sabinene (3.1–21.3%), myrcene (6.0–18.8%), (E)‐β‐ocimene (1.8–27.2%) and (Z)‐β‐ocimene (0.1–17.2%). Copyright © 2001 John Wiley & Sons, Ltd.
Dealing with pressure: FEM solution strategies for the pressure in the time‐dependent Navier–Stokes equations
Authors: Christon Mark A.
Published: August 2002

This paper presents a survey of solution methods for calculating the pressure in the time‐dependent Navier–Stokes equations. The primary focus is on the treatment of the pressure‐Poisson equation deriving from index‐1 DAE formulations of the Navier–Stokes equations. Based on extensive operational experience with a variety of solution strategies, the combination of a stabilized pressure‐Poisson operator with an A‐conjugate projection and SSOR preconditioned conjugate gradient method has been found to yield the overall best performance relative to the resolve cost of a high performance direct solver. Copyright © 2002 John Wiley & Sons, Ltd.
Fluorescence in situ hybridization analyses of chromosome band 1p36 in neuroblastoma detect two classes of alterations
Authors: Spitz Ruediger , Hero Barbara , Westermann Frank , Ernestus Karen , Schwab Manfred , Berthold Frank
Published: August 2002

Chromosomal alterations in 1p36 were investigated in 196 neuroblastoma tumors using fluorescence in situ hybridization. Additionally, by using the same technique, it was determined whether MYCN was amplified in 149 of these. The most frequent finding was a deletion in 1p36, leading to monosomy of this region (29 cases, 15%). Furthermore, we found tumors with at least two intact copies of chromosome 1 and additional 1p36‐deleted copies. Altogether, 21 tumors (11%) displayed this imbalance of 1p36. Similar to the cases with deletion, imbalances were predominantly found in stage 4 tumors (81%), and they were significantly associated with an increased patient age (P = 0.01). Nearly all 1p‐deleted tumors showed amplification of MYCN (24/27 analyzed samples, 89%), whereas only 8 of 21 (38%) with imbalance did. Eight cases with imbalance were investigated for loss of heterozygosity (LOH) using microsatellite markers in 1p35–36. Only 4 displayed 1p36 LOH, whereas the remaining 4 were heterozygous. Both patients with deletion of 1p and with imbalance had a poor outcome [3‐year rate of event‐free‐survival (EFS): 33±15% and 41±15%], which was significantly worse compared to the outcome of patients without 1p alterations (3‐year EFS: 70±5%; P = 0.01 and P = 0.0059). We conclude that besides monosomic short arm deletions, imbalance of 1p36 is a strong marker of a poor prognosis in neuroblastoma and not necessarily associated with MYCN amplification and LOH. © 2002 Wiley‐Liss, Inc.
Molecular cytogenetic characterization of early and late renal cell carcinomas in Von Hippel‐Lindau disease
Authors: Phillips John L. , Ghadimi B. Michael , Wangsa Danny , Padilla‐Nash Hesed , Worrell Robert , Hewitt Steven , Walther McClellan , Linehan W. Marston , Klausner Richard D. , Ried Thomas
Published: August 2002

Deletions of 3p25, gains of chromosomes 7 and 10, and isochromosome 17q are known cytogenetic aberrations in sporadic renal cell carcinoma (RCC). In addition, a majority of RCCs have loss of heterozygosity (LOH) of the Von Hippel‐Lindau (VHL) gene located at chromosome band 3p25. Patients who inherit a germline mutation of the VHL gene can develop multifocal RCCs and other solid tumors, including malignancies of the pancreas, adrenal medulla, and brain. VHL tumors follow the two‐hit model of tumorigenesis, as LOH of VHL, a classic tumor suppressor gene, is the critical event in the development of the neoplastic phenotype. In an attempt to define the cytogenetic aberrations from early tumors to late RCC further, we applied spectral karyotyping (SKY) to 23 renal tumors harvested from 6 unrelated VHL patients undergoing surgery. Cysts and low‐grade solid lesions were near‐diploid and contained 1–2 reciprocal translocations, dicentric chromosomes, and/or isochromosomes. A variety of sole numerical aberrations included gains of chromosomes 1, 2, 4, 7, 10, 13, 21, and the X chromosome, although no tumors had sole numerical losses. Three patients shared a breakpoint at 2p21–22, and three others shared a dicentric chromosome 9 or an isochromosome 9q. In contrast to the near‐diploidy of the low‐grade lesions, a high‐grade lesion and its nodal metastasis were markedly aneuploid, revealed loss of VHL by fluorescence in situ hybridization (FISH), and contained recurrent unbalanced translocations and losses of chromosome arms 2q, 3p, 4q, 9p, 14q, and 19p as demonstrated by comparative genomic hybridization (CGH). By combining SKY, CGH, and FISH of multiple tumors from the same VHL kidney, we have begun to identify chromosomal aberrations in the earliest stages of VHL‐related renal cell tumors. Our current findings illustrate the cytogenetic heterogeneity of different VHL lesions from the same kidney, which supports the multiclonal origins of hereditary RCCs. Published 2001 Wiley‐Liss, Inc.
Differential regulation of glial cell line‐derived neurotrophic factor (GDNF) mRNA expression during hypoxia and reoxygenation in astrocytes isolated from stroke‐prone spontaneously hypertensive rats
Authors: Yamagata Kazuo , Tagami Motoki , Ikeda Katsumi , Tsumagari Shigehisa , Yamori Yukio , Nara Yasuo
Published: August 2002

Glial cell line‐derived neurotrophic factor (GDNF) plays several important roles in the survival and recovery of mature neurons during ischemia. We examined the possibility that the expression of GDNF mRNA and the release of GDNF protein are regulated differentially in cultured astrocytes from the stroke‐prone spontaneously hypertensive rat (SHRSP) compared with those from Wistar Kyoto rats (WKY) during hypoxia and reoxygenation (H/R) and after exposure to glutamate and hydrogen peroxide (H2O2). The mRNA expression was quantitated by reverse transcription‐polymerase chain reaction (RT‐PCR) based on the fluorescent TaqMan methodology. A new instrument capable of measuring fluorescence in real‐time was used to quantify gene amplification in astrocytes. GDNF protein was investigated by enzyme‐linked immunosorbent assay (ELISA). GDNF mRNA expression and GDNF protein release at normoxia were greater in SHRSP than in WKY astrocytes. During H/R, however, the mRNA expression and protein release tended to be reduced in SHRSP compared with WKY. Glutamate and H2O2 induced the expression of GDNF mRNA and the release of GDNF protein in both WKY and SHRSP in a dose‐dependent manner. Levels of GDNF mRNA and protein in SHRSP were significantly lower than in WKY. These findings indicate that GDNF production in SHRSP astrocytes was low in response to H/R, glutamate, and H2O2, compared with that observed in WKY. We conclude that the attenuated production of GDNF in astrocytes is involved in neuronal vulnerability in SHRSP during H/R, as GDNF production, which is stimulated by glutamate and H2O2, is closely related to the protective effect against H/R‐mediated neurotoxicity. GLIA 37:1–7, 2002. © 2002 Wiley‐Liss, Inc.
The benefits of a broader perspective in case‐finding for disease management of depression: early lessons from the PROSPECT Study†
Authors: Coyne James C. , Brown Gregory , Datto Catherine , Bruce Martha L. , Schulberg Herbert C. , Katz Ira
Published: August 2002

The PROSPECT (Prevention of Suicide in Primary Care Elderly — Collaborative Trial) Study evaluates collaborative care for the treatment of current depressive disorders in older primary care patients. Using screening data, we evaluate implications of expanding the focus to additional patients who report taking psychotropic medication or having a history of depression. Some 13.8% of the patients screened were taking a psychotropic medication and 7.3% were both taking an antidepressant and had a Center for Epidemiologic Studies — Depression Scale (CES‐D) score of > 15. Patients who reported current antidepressant use and those with a history of depression also had elevated CES‐D scores. Conversely, most patients having an elevated CES‐D score also reported taking an antidepressant or having a history of depression. These latter criteria for potential caseness yielded a larger number of patients than those identified by the CES‐D alone. More comprehensive approaches to the management of depression should attend to patients already taking psychotropic medication and symptomatic patients with a history of depression, as well as those with current syndromal depression. Copyright © 2001 John Wiley & Sons, Ltd.
A double‐blind randomised comparison of risperidone and haloperidol in the treatment of behavioural and psychological symptoms in Chinese dementia patients
Authors: Chan Wai‐chi , Lam Linda Chiu‐wa , Choy Caroline Nga‐pui , Leung Vivian Pui‐yiu , Li Siu‐wah , Chiu Helen Fung‐kum
Published: August 2002

Background

Behavioural and psychological symptoms (BPSD) are common during the course of dementia and present severe problems to patients and their caregivers.

Objectives

To assess the therapeutic efficacy and safety of haloperidol and risperidone in treating BPSD in Chinese dementia patients.

Methods

A 12‐week double‐blind randomised comparison of haloperidol and risperidone treatments was conducted in 58 patients with DSM‐IV diagnosis of dementia of Alzheimer's type or vascular dementia. They were randomly assigned to receive flexible doses (0.5 to 2 mg/day) of haloperidol or risperidone. Clinical response was evaluated using the Cohen‐Mansfield Agitation Inventory (CMAI), the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE‐AD), Simpson‐Angus Scale, Functional Assessment Staging and Cantonese version of the Mini‐Mental State Examination.

Results

The mean doses at the last week were 0.90 mg/day of haloperidol and 0.85 mg/day of risperidone. Both haloperidol and risperidone significantly reduced the severity of BPSD (scores on CMAI and BEHAVE‐AD), with no significant between‐group differences. Haloperidol‐treated patients showed a worsening on Simpson‐Angus scale while there was no significant change in this measure in risperidone‐treated patients.

Conclusions

Low‐dose haloperidol and risperidone were well tolerated and associated with reductions in the severity and frequency of behavioural symptoms in subjects with dementia. Risperidone may have a more favourable risk‐benefit profile in view of its lower propensity to induce extrapyramidal symptoms. Copyright © 2001 John Wiley & Sons, Ltd.
A facile one‐pot regioselective synthesis of [1,2,4]triazolo[4,3‐a]5(1H)‐pyrimidinones via tandem Japp–Klingemann, Smiles rearrangement, and cyclization reactions
Authors: Shawali Ahmad S. , Abdallah Magda A. , Mosselhi Mosselhi A. N. , Farghaly Thoraya A.
Published: August 2002

Coupling of active [(4‐oxo‐6‐phenyl‐3H‐pyrimidin‐2‐yl)thio]methine compounds (3) with diazotized anilines in the presence of base gave [1,2,4]triazolo[4,3‐a]pyrimidines (7). The latter products were also obtained by reactions of hydrazonoyl chlorides (10) with either 6‐phenyl‐2‐thiouracil (1) or the 2‐methylthio derivative 9. The mechanisms and the regiochemistry of the reactions studied are discussed. © 2002 Wiley Periodicals, Inc. Heteroatom Chem 13:136–140, 2002; Published online in Wiley Interscience (www.interscience.wiley.com). DOI 10.1002/hc.10008
Functionally substituted alkylbenzotriazoles: Reactivity of alkylbenzotriazoles toward electrophilic and nucleophilic reagents
Authors: Al‐Saleh Balkis , Abdel‐Khalik Mervat Mohammed , Darwich Elham , Salah Ossama Abdel‐Motaleb , Elnagdi Mohammed Hilmy
Published: August 2002

The reactivity of benzotriazolylacetone toward a variety of carbon and nitrogen electrophiles is reported. Several novel azolylbenzotriazoles as well as benzotriazolyl‐cinnolines have been synthesized. © 2002 Wiley Periodicals, Inc. Heteroatom Chem 13:141–145, 2002; Published online in Wiley Interscience (www.interscience.wiley.com). DOI 10.1002/hc.10009
Azabrendanes. III. Synthesis of stereoisomeric exo‐ and endo‐5‐acylaminomethyl‐exo‐2,3‐epoxybicyclo[2.2.1]heptanes and their reduction by lithium aluminum hydride
Authors: Kasyan Lilija I. , Tarabara Igor N. , Savel'yeva Oxana A. , Kasyan Andrey O.
Published: August 2002

A number of stereoisomeric N‐[aryl(alkyl, cycloalkyl)carbonyl]‐exo(endo)‐5‐aminomethylbicyclo[2.2.1]hept‐2‐enes have been synthesized from bicyclo[2.2.1]hept‐2‐en‐exo(endo)‐5‐carbonitrile via reduction of the latter by lithium aluminum hydride and subsequent reactions of the resulting amines with aryl(alkyl, cycloalkyl)carbonyl chlorides and anhydrides. The direction of reaction of amides with peroxy acids does not depend on orientation of substituents in the bicyclic fragment: that is, for both exo‐ and endo‐isomers the epoxidations are completed by the formation of N‐[aryl(alkyl, cycloalkyl)carbonyl]‐exo(endo)‐5‐aminomethyl‐exo‐2,3‐epoxybicyclo[2.2.1] heptanes. The reduction of stereoisomeric epoxides by lithium aluminium hydride proceeds in different directions; that is, isomers with an exo‐oriented amido group form the substituted exo‐5‐alkylaminomethyl‐exo‐2,3‐epoxybicyclo[2.2.1]heptanes and the reactions of epoxides of endo‐amides are accompanied by intramolecular cyclization and completed by the
formation of N‐[aryl(alkyl, cycloalkyl)]‐exo‐2‐hydroxy‐4‐azatricyclo[4.2.1.03,7]nonanes. The structures and stereochemical homogenity of the products have been confirmed by the analysis of 1H and 13C NMR spectra, correlation spectroscopy, and nuclear Overhauser enhancement spectroscopy experiments. We discuss the behavior of epoxides and provide an analysis of the coefficients of the atomic orbitals in the molecular orbital–linear combination of atomic orbitals equation (AM1 method). © 2001 John Wiley & Sons, Inc. Heteroatom Chem 12:119–130, 2001
Unit root properties of OECD health care expenditure and GDP data
Authors: MacDonald Garry , Hopkins Sandra
Published: August 2002

This note reconsiders the unit root properties of health care expenditure (HCE) and gross domestic product (GDP) for OECD countries. The time‐series properties of this data set has been much discussed in the literature with contrasting results from the application of a range of test procedures. We use a recently developed test to examine the relationship between the two variables. The results in this paper confirm earlier findings that when the data are considered as a panel, there is strong evidence of unit roots in both GDP and HCE data. Copyright © 2001 John Wiley & Sons, Ltd.