bluuebunny/crossref_metadata_2025 huggingface dataset:
Preliminary observations on the influence of rheumatoid alpha‐1‐acid glycoprotein on collagen fibril formation
Authors: Haston J. Louise , FitzGerald Oliver , Kane David , Smith Kevin D.
Published: August 2002

This study investigates the effect of α1‐acid glycoprotein (AGP) isolated from both normal and rheumatoid plasma on type II collagen fibril formation. Rheumatoid samples were obtained over 2 years from two patients with early arthritis. The glycosylation of each sample was analysed to establish any correlation with fibrillogenesis. Rheumatoid AGP displays increased fucosylation compared to normal AGP. In both patients the fucosylation dipped after 1 year, then rose again over year 2. It is proposed that year 1 corresponds to the acute phase of the disease and the onset of chronic inflammation after this time produces a subsequent increase in fucosylation. Rheumatoid AGP influences type II collagen fibrillogenesis. Native fibrils were produced but with differences in the rate and extent of fibrillogenesis depending on AGP concentration and fucosylation. Low concentrations produced a decrease in fibrillogenesis rate and fibril diameter. High concentrations produced fibrils at a rate and diameter dependent on fucosylation. Highly fucosylated AGP produced narrow fibrils slowly, whereas poorly fucosylated AGP produced thicker fibrils more quickly. We propose that differences in glycosylation (especially fucosylation) of AGP are responsible for differences in collagen fibrillogenesis and this phenomenon may contribute to the exacerbation of cartilage destruction in rheumatoid arthritis. Copyright­© 2002 John Wiley & Sons, Ltd.
LC‐ESI‐MS analysis of taxoids from the bark of Taxus wallichiana
Authors: Madhusudanan K. P. , Chattopadhyay S. K. , Tripathi V. K. , Sashidhara K. V. , Kukreja A. K. , Jain S. P.
Published: August 2002

LC‐ESI‐MS analysis was carried out for taxoid profiling of partially purified methanol extracts of the stem bark of Taxus wallichiana growing in different regions of the Himalayas (Kashmir, Himachal Pradesh, UP hills, Sikkim and Arunachal Pradesh). Cone voltage fragmentation of the protonated, ammonium or sodium cationized molecular species resulted in diagnostic fragment ions. Thus, information about the number and nature of substituents and the taxane skeleton (whether it is normal or rearranged) was readily available from the LC‐ESI‐MS spectra. The rearranged 11(15→1)‐abeo‐taxanes showed a characteristic elimination of the hydroxyisopropyl along with an acetoxy group. The identification of the taxoids was achieved by comparison of the ESI mass spectra with those of the authentic taxoids available to us or by interpreting the ESI mass spectra. The results were also corroborated by MS/MS analysis of the partially purified extract injected directly into the ESI source. Paclitaxel, its analogues and their xylosides are present in samples from all the regions. An interesting observation is the detection of a large number of basic taxoids having nitrogen‐containing side chains. Copyright © 2002 John Wiley & Sons, Ltd.
Anomalous muscle of the wrist
Authors: Ragoowansi R. , Adeniran A. , Moss A.L.H.
Published: August 2002

A case of an anomalous muscle found in the right wrist of a 52‐year‐old man during routine carpal tunnel decompression surgery is reported. The muscle was observed lying transversely across the carpal tunnel superficial and parallel to the flexor retinaculum. Its further definition was subsequently demonstrated by postoperative magnetic resonance imaging (MRI). No similar structure was detectable on MRI of the left wrist. Clin. Anat. 15:363–365, 2002. © 2002 Wiley‐Liss, Inc.
Correlation of Web usage and exam performance in a human anatomy and development course
Authors: Rizzolo Lawrence J. , Aden Marcus , Stewart William B.
Published: August 2002

Course materials for a Human Anatomy and Development Course were placed on the World Wide Web (WWW). The materials included a lab manual, lecture notes and slides, faculty‐generated atlases, Web links, and examinations. The lab manual, lecture notes, and atlases were also provided as black‐and‐white hardcopy. The Office of Education assigned students a code name that allowed them to use the Web site and take exams anonymously. Student Web use was tracked and correlated with their performance on the final examination. Overall use patterns revealed that most students used the Web site to prepare for examinations, but not for daily studying. Old examinations were the most accessed documents; lecture notes were the least accessed. The access patterns of the students with top 20, middle 20 (closest to the mean), and bottom 20 scores on the final examination were compared. In general, there was little difference between the middle and top groups. Students in the bottom group used computer resources significantly less than the other groups. In a second analysis, the 10 students who used the Web site most frequently scored below the mean. The study suggests that interactive exercises will be heavily used, but that the preparation of all course materials for the WWW may not be an efficient use of institutional resources. Clin. Anat. 15:351–355, 2002. © 2002 Wiley‐Liss, Inc.
Giving color to a new curriculum: Bodypaint as a tool in medical education
Authors: Op Den Akker J.W. , Bohnen A. , Oudegeest W.J. , Hillen B.
Published: August 2002

We describe a new method, bodypainting, to enhance courses in living anatomy. This novel approach was fully integrated in a course that comprised gross anatomy, living anatomy, and physical examination of the major abdominal and thoracic organs. We designed a course in which the students familiarized themselves with the surface markings and subsequently painted the full organ at the site of its projection on the body surface. Based on our first experiences, we conclude that the course is a successful and enjoyable means of teaching various aspects of anatomy in relation to physical examination. This was confirmed by an evaluation among the first groups of students. Clin. Anat. 15:356–362, 2002. © 2002 Wiley‐Liss, Inc.
Morphometric study of testis of Wistar rat after open‐ended vasectomy
Authors: Whyte J. , Cisneros A.I. , Rubio E. , Whyte A. , Mazo R. , Torres A. , Sarrat R.
Published: August 2002

The effects on the testis of open‐ended vasectomy in the Wistar rat have been assessed morphometrically and evaluated statistically at 1, 4, 12, and 24 weeks after operation, and compared to those in sham‐operated controls. The open‐ended technique, ie, without ligation of the epididymal end of the cut ductus deferens, allowed drainage of sperm into the spermatic cord. During the period of our study, it did not affect the structure of the testis; although the germinal epithelium, basement membrane, and the stroma and cells of the interstitial space all showed variations when compared to the control group, these were not statistically significant. Clin. Anat. 15:335–339, 2002. © 2002 Wiley‐Liss, Inc.
Coexistence of a pectoralis quartus muscle and an unusual axillary arch: Case report and review
Authors: Bonastre Victoria , Rodríguez‐Niedenführ Marc , Choi David , Sañudo José R.
Published: August 2002

A pectoralis quartus muscle and an unusual axillary arch were found on the left side of a female cadaver. The axillary arch was a musculoaponeurotic complex continuous with the iliacal fibers of the latissimus dorsi. The muscular part, together with the tendon of pectoralis major, inserted into the lateral lip of the bicipital groove of the humerus, whereas the aponeurotic part was formed by a fibrous band that extended deep to the pectoralis major to insert into the coracoid process between the attachments of the coracobrachialis and pectoralis minor. The pectoralis quartus originated from the rectus sheath, and joined the inferior medial border of the fibrous band of the axillary arch, at the lateral edge of the pectoralis major. The axillary arch muscle crossed anteriorly the axillary vessels and the brachial plexus. The clinical importance of these muscles is reviewed. Clin. Anat. 15:366–370, 2002. © 2002 Wiley‐Liss, Inc.
α2‐Heremans Schmid glycoprotein, a putative inhibitor of tyrosine kinase, prevents glucose toxicity associated with cardiomyocyte dysfunction
Authors: Ren Jun , Davidoff Amy J.
Published: August 2002

Background

Diabetes leads to impaired glucose metabolism and insulin signaling in the heart, which may contribute to the development of diabetic cardiomyopathy. Insulin stimulates tyrosine phosphorylation of the insulin receptor and insulin receptor substrates. A two‐fold increase in insulin‐stimulated tyrosine phosphorylation has been reported in diabetic myocardium. The aim of the present study was to examine the effect of a putative inhibitor of tyrosine kinase phosphorylation, α2‐Heremans Schmid glycoprotein (AHSG), on the mechanical dysfunction under a simulated diabetic environment.

Methods

Isolated ventricular myocytes from adult rats were maintained for 24 h in either normal glucose (NG, 5.5 mM) or high glucose (HG, 25.5 mM) medium with 10−7 M insulin, and in the absence or presence of AHSG (50 µg/ml). Contractile indices analyzed included: peak shortening (PS), time‐to‐PS (TPS), time‐to‐90% relengthening (TR90) and area underneath shortening and relengthening (Area/PS).

Results

Myocytes maintained in HG medium displayed reduced PS and prolonged TPS/TR90, with enhanced area, compared to the NG myocytes. Interestingly, these HG‐induced mechanical dysfunctions were abolished by AHSG. Removal of insulin from the culture medium did not affect the basal myocyte mechanics, but prevented AHSG from completely protecting against the HG‐induced mechanical defects (i.e. HG‐induced prolongation of TR90 and area were only partially attenuated by AHSG in the absence of insulin).

Conclusions

The present data support the notion of tyrosine phosphorylation in the pathogenesis of diabetic cardiomyopathy, and implicate the therapeutic value of tyrosine kinase phosphorylation inhibitors. Copyright © 2002 John Wiley & Sons, Ltd.
Neurovascular disease, antioxidants and glycation in diabetes
Authors: Dickinson P. J. , Carrington A. L. , Frost G. S. , Boulton A. J. M.
Published: August 2002

People with diabetes are ten to fifteen times more likely to have a lower limb amputation (LLA) than non‐diabetic individuals. Fifteen percent of people with diabetes will develop a foot ulcer during their lifetime, the rate of major amputation amongst diabetic individuals continues to rise, foot problems remain the commonest reason for diabetes‐related hospitalisation and recurrence rates in patients with previous foot ulcers are 50% or more. Hyperglycaemia‐induced oxidative stress has been shown to result in decreased nerve conduction velocity, and decreased endoneural blood flow—both precursors for neuropathy. Vitamin antioxidants have been shown to be effective therapy in experimental models in reducing free radical species and inhibiting the oxidative process in diabetes subjects. Little work has been published, however, regarding the dietary use of antioxidants from foods, and their specific effects on neurovascular disease and glycation within the diabetes population. Aetiological and prevention studies with dietary antioxidants from foods aimed at the complex nature of foot problems in diabetes are needed. Copyright © 2002 John Wiley & Sons, Ltd.
The influence of teacher expectations on student achievement in physical education classes: Pygmalion revisited
Authors: Trouilloud David O. , Sarrazin Philippe G. , Martinek Thomas J. , Guillet Emma
Published: August 2002

The main purpose of this study was to explore the relation between teacher expectations and student achievement in physical education classes, in the light of three complementary hypotheses. Student achievement may confirm teacher expectations because these expectations create self‐fulfilling prophecies, create perceptual biases, or accurately predict, without influencing, student achievement (Jussim,1989). Another purpose was to examine the mediating role played by students' perceived ability in the teacher expectancy process. Study data were obtained from 173 students and 7 teachers. Path analysis revealed that teacher expectations have weak self‐fulfilling effects, strongly predicted student achievement mainly because they are accurate, and have no biasing effects on teacher judgements. Results also show evidence concerning the role of partial mediator of perceived student ability in the confirmation process of teacher expectations. Copyright © 2002 John Wiley & Sons, Ltd.
Relative effectiveness of differently framed health messages: the influence of ambivalence
Authors: Broemer Philip
Published: August 2002

The present studies test the hypothesis that the degree of experienced ambivalence toward health behaviors moderates the impact of differently framed messages. In line with prospect theory, it is argued that positive frames can either involve attaining desirable outcomes or avoiding undesirable outcomes, and negative frames can either emphasize the presence of undesirable outcomes or the absence of desirable outcomes. The results of three studies are supportive of the hypothesis that highly ambivalent individuals are more persuaded by negatively framed messages whereas individuals low in ambivalence are more persuaded by positively framed messages. The greater persuasiveness of negatively framed messages at higher levels of ambivalence can be explained by a negativity bias involved in ambivalence. Several preventive behaviors such as eating a low‐fat diet or using condoms were addressed. Theoretical and practical implications of these findings are discussed in light of current theories on health behavior. Copyright © 2002 John Wiley & Sons, Ltd.
Moderator effects of attitudinal ambivalence on attitude–behaviour relationships
Authors: Conner Mark , Sparks Paul , Povey Rachel , James Rhiannon , Shepherd Richard , Armitage Christopher J.
Published: August 2002

Attitudinal ambivalence is generally construed as existing when the same attitude object is evaluated simultaneously as both positive and negative. The present research examined the moderating role of attitudinal ambivalence (as assessed by split‐semantic differential measure) on the relationship between bipolar semantic differential measures of attitude and subsequent behaviour using moderated regression analysis. In Study 1, higher levels of attitudinal ambivalence were shown to result in weaker attitude–behaviour relationships for eating a low‐fat diet (N = 140) and eating 5 portions of fruit and vegetables per day (N = 142). Study 2 (N = 361) replicated this effect when also including a measure of past behaviour for eating a low‐fat diet. Implications for understanding the relationship between attitudes and behaviour are discussed. Copyright © 2002 John Wiley & Sons, Ltd.
Attachment styles in everyday social interaction
Authors: Kafetsios Konstantinos , Nezlek John B.
Published: August 2002

For seven days, participants described the important interactions they had using a variant of the Rochester Interaction Record and reported their attachment style using Bartholomew's four‐category system. A series of multilevel random coefficient analyses found that across all interactions securely attached participants, compared to those who were insecurely attached, found their interactions to be more intimate and more positive emotionally. Secure participants also felt that others were more responsive to them and their needs. Secure–insecure differences were most pronounced when secure and dismissive avoidant participants were compared. Differences between secure and fearful types were minimal. In contrast, differences in reactions to interactions with close and not close friends were more pronounced for fearful types than for secures, dismissing, or preoccupied types. These results highlight the importance of distinguishing fearful and dismissive avoidance. Copyright © 2002 John Wiley & Sons, Ltd.
Towards a direct collapse–load method of design for concrete frames subjected to severe ground motions
Authors: Griffith M. C. , Kawano A. , Warner R. F.
Published: August 2002

Most current methods of design for concrete structures under earthquake loads rely on highly idealized ‘equivalent’ static representations of the seismic loads and linear‐elastic methods of structural analysis. With the continuing development of non‐linear methods of dynamic analysis for the overload behaviour and collapse of complete concrete structures, a more direct and more accurate design procedure becomes possible which considers conditions at system collapse. This paper describes an evaluation procedure that uses non‐linear dynamic collapse–load analysis together with global safety coefficients. A back‐calibration procedure for evaluating the global safety coefficients is also described. The aim of this paper is to open up discussion of alternative methods of design with improved accuracy which are necessary to move towards a direct collapse–load method of design. Copyright © 2002 John Wiley & Sons, Ltd.
Defining phases of bedload transport using piecewise regression
Authors: Ryan Sandra E. , Porth Laurie S. , Troendle C. A.
Published: August 2002

Differences in the transport rate and size of bedload exist for varying levels of flow in coarse‐grained channels. For gravel‐bed rivers, at least two phases of bedload transport, with notably differing qualities, have been described in the literature. Phase I consists primarily of sand and small gravel moving at relatively low rates over a stable channel surface. Transport rates during Phase II are considerably greater than Phase I and more coarse grains are moved, including material from both the channel surface and subsurface. Transition from Phase I to Phase II indicates initiation and transport of grains comprising the coarse surface layer common in steep mountain channels. While the existence of different phases of transport is generally acknowledged, the threshold between them is often poorly defined. We present the results of the application of a piecewise regression analysis to data on bedload transport collected at 12 gravel‐bed channels in Colorado and Wyoming, USA. The piecewise regression recognizes the existence of different linear relationships over different ranges of discharge. The inflection, where the fitted functions intersect, is interpreted as the point of transition from Phase I to Phase II transport; this is termed breakpoint. A comparison of grain sizes moved during the two phases shows that coarse gravel is rarely trapped in the samplers during Phase I transport, indicating negligible movement of grains in this size range. Gravel larger than about D16 of the channel surface is more consistently trapped during Phase II transport. The persistence of coarse gravel in bedload samples provides good evidence that conditions suitable for coarse grain transport have been reached, even though the size of the sediment approaches the size limits of the sampler (76 mm in all cases). A relative breakpoint (Rbr) was defined by the ratio between the discharge at the breakpoint and the 1·5‐year flow (a surrogate for bankfull discharge) expressed as a percentage. The median value of Rbr was about 80 percent, suggesting that Phase II begins at about 80 percent of the bankfull discharge, though the observed values of Rbr ranged from about 60 to 100 percent. Variation in this value appears to be independent of drainage area, median grain size, sorting of bed materials, and channel gradient, at least for the range of parameters measured in 12 gravel‐bed channels. Published in 2002 by John Wiley & Sons, Ltd.
Sediment yield and storage variations in the Négron River catchment (south western Parisian Basin, France) during the Holocene period
Authors: Macaire Jean‐Jacques , Bellemlih Saïda , Di‐Giovanni Christian , De Luca Patrick , Visset Lionel , Bernard Jacques
Published: August 2002

In the Négron River catchment area (162 km2), surface‐sediment stores are composed of periglacial calcareous ‘grèze’ (5 × 106t) and loess (21 × 106t), and Holocene alluvium (12·6 × 106t), peat (0·6 × 106t) and colluvium (18·5 × 106t). Seventy‐five per cent of the Holocene sediments is stored along the thalwegs. Present net sediment yield, calculated from solid discharge at the Négron outlet, is low (0·6 t km−2a−1) due to the dominance of carbonate rocks in the catchment. Mean sediment yield during the Holocene period is 7·0 t km−2a−1from alluvium stores and 7·6 t km−2a−1from colluvium stores. Thus, the gross sediment yield during the Holocene period is about 18·7 t km−2a−1and the sediment delivery ratio 3 per cent. The yield considerably varies from one sub‐basin to another (3·9 to 24·5 t km−2a−1) according to lithology: about 25 per cent and 50 per cent of initial stores of periglacial grèze and loess respectively were reworked during the Holocene period. Sediment yield has increased by a factor of 6 in the last 1000 years, due to the development of agriculture. The very high rate of sediment storage on the slope during that period (88 per cent of the yield) can be accounted for by the formation of cultivation steps (‘rideaux’). It is predicted that the current destruction of these steps will result in a sediment wave reaching the valley floors in the coming decades. Subboreal and Subatlantic sediments and pollen assemblages in the Taligny marsh, where one‐third of the alluvium is stored, show the predominant influence of human activity during these periods in the Négron catchment. Copyright © 2002 John Wiley & Sons, Ltd.
Organizational responses to a changing aid environment: the German Agency for Technical Cooperation (GTZ)
Authors: Hill Peter S.
Published: August 2002

As a major European donor, German government development assistance faces a series of challenges. Recent political changes have raised expectations for demonstrable health outcomes as a result of German development assistance; there has been a deepened commitment to collaboration with other bilateral and multilateral donors; and partner countries are increasingly open to new approaches to development. German development assistance also reflects a new ethos of partnership and the shift to programmatic and sector based development approaches. At the same time, its particular organizational structure and administrative framework highlight the extent of structural and systems reforms required of donors by changing development relationships, and the tensions created in responding to these.

This paper examines organizational changes within the German Agency for Technical Cooperation (Deutsche Gesellschaft für Technische Zusammenarbeit) (GTZ), aimed at increasing its Regional, Sectoral, Managerial and Process competence as they affect health and related sectors. These include the decentralization of GTZ, the trend to integration of projects, the increasing focus on policy and health systems reform, increased inter‐sectoral collaboration, changes in recruitment and training, new perspectives in planning and evaluation and the introduction of a quality management programme. Copyright © 2002 John Wiley & Sons, Ltd.
Patient based ‘burden‐of‐illness’ in Swedish primary health care. Applying the Johns Hopkins ACG case‐mix system in a retrospective study of electronic patient records
Authors: Carlsson L. , Börjesson U. , Edgren L.
Published: August 2002

Patients from one municipality in Sweden utilizing primary health care (PHC) during 1998 and 1999 have been categorized into 81 groups. The groups show each patient's own case‐mix in terms of illness. Grouping was carried out using the case‐mix instrument adjusted clinical groups (ACG), developed by the School of Hygiene and Public Health at Johns Hopkins University in Baltimore, USA. The resulting pattern provided a more adequate reflection of the scope of primary care's task than that yielded by diagnoses alone. Changes over time in terms of illness patterns for a population could be described, analysed and assessed from medical and health economic perspectives. One of the conclusions from this study was that the ACG instrument is a relevant tool in describing the outcome of work by the primary health care centre. The ACG is of interest in the improvement of the quality of primary care in Sweden. The ACG should be a driving force in the development of health indices in both national and international comparisons, as a result of its focus on the health status of patients and populations instead of on diagnoses and diseases. Copyright © 2002 John Wiley & Sons, Ltd.
The limits to patient compliance with directly observed therapy for tuberculosis: a socio‐medical study in Pakistan
Authors: Meulemans H. , Mortelmans D. , Liefooghe R. , Mertens P. , Akbar Zaidi S. , Farooq Solangi M. , De Muynck A.
Published: August 2002

Complying with the prescriptions of the directly observed therapy (DOT), one of the components of the Global Tuberculosis Programme of the WHO, is problematic for many patients. The factors leading to patient (non‐) compliance with DOT are placed in a structural equation model.

The study is based on a survey carried out in one general hospital in the Punjab province of Pakistan, amongst all sputum positive pulmonary TB patients (n = 621) who arrived at the TB unit from September 1997 to October 1998.

The tested sequence of manifest variables and latent constructs shows that the social stratification perspective has to be extended by the stigmatization perspective. The advantages of universally applying DOT will increase even further when the latter perspective is involved in the analysis of non‐compliance. There is a real danger that the patients reached by selective DOT will be stigmatized even more. Copyright © 2002 John Wiley & Sons, Ltd.
Meta‐iodobenzylguanidine induces growth inhibition and apoptosis of neuroendocrine gastrointestinal tumor cells
Authors: Höpfner Michael , Sutter Andreas P. , Beck Nikolai I. , Barthel Bettina , Maaser Kerstin , Jockers‐Scherübl Maria C. , Zeitz Martin , Scherübl Hans
Published: August 2002

Neuroendocrine gastrointestinal tumors take up, decarboxylate and store large amounts of monoamines. Radioactive‐labeled monoamines like the norepinephrine analogue meta‐iodobenzylguanidine (MIBG) have been used for the imaging of neuroendocrine tumors for many years. MIBG is selectively taken up via norepinephrine transporters (NETs) localized in the plasma membrane of neuroendocrine gastrointestinal tumor cells and thereby offers the possibility for specific and innovative therapeutic approaches. We investigated the antiproliferative, cytotoxic, cell cycle‐arresting and apoptosis‐inducing effects of MIBG in the neuroendocrine gastrointestinal tumor cell line STC‐1 and for control in the nonneuroendocrine colorectal cancer cell line HT‐29. RT‐PCR revealed the expression of NET in STC‐1 but not in HT‐29 cells. MIBG dose‐dependently induced cytotoxicity and growth inhibition of STC‐1 cells. It potently induced apoptosis in STC‐1 cells as assessed by changes in the mitochondrial membrane potential, activation of caspase‐3 and DNA fragmentation. Moreover, MIBG altered the expression of several genes involved in proliferation, apoptosis and stress responses as shown by cDNA arrays. In contrast, neither cytotoxicity, nor growth inhibition nor induction of apoptosis were detected in response to MIBG in the NET‐deficient colorectal cancer cell line HT‐29. Our data show that MIBG induces growth inhibition and apoptosis in neuroendocrine gastrointestinal tumor cells. MIBG did not arrest the cell cycle in either cell line. Thus, monoamine transporters in the plasma membrane of neuroendocrine gastrointestinal tumor cells are promising targets for innovative and specific treatment strategies of these tumors. © 2002 Wiley‐Liss, Inc.
Inhibition of the mammary carcinoma angiogenic switch in C3(1)/SV40 transgenic mice by a mutated form of human endostatin
Authors: Calvo Alfonso , Yokoyama Yumi , Smith Lois E. , Ali Iqbal , Shih Shu‐Ching , Feldman Andrew L. , Libutti Steven K. , Sundaram Ramakrishnan , Green Jeffrey E.
Published: August 2002

Cancer therapies based on the inhibition of angiogenesis by endostatin have recently been developed. We demonstrate that a mutated form of human endostatin (P125A) can inhibit the angiogenic switch in the C3(1)/Tag mammary cancer model. P125A has a stronger growth‐inhibitory effect on endothelial cell proliferation than wild‐type endostatin. We characterize the angiogenic switch, which occurs during the transition from preinvasive lesions to invasive carcinoma in this model, and which is accompanied by a significant increase in total protein levels of vascular endothelial growth factor (VEGF) and an invasion of blood vessels. Expression of the VEGF188 mRNA isoform, however, is suppressed in invasive carcinomas. The VEGF receptors fetal liver kinase‐1 (Flk‐1) and Fms‐like tyrosine kinase‐1 (Flt‐1) become highly expressed in epithelial tumor and endothelial cells in the mammary carcinomas, suggesting a potential autocrine effect for VEGF on tumor cell growth. Angiopoietin‐2 mRNA levels are also increased during tumor progression. CD‐31 (platelet‐endothelial cell adhesion molecule [PECAM]) staining revealed that blood vessels developed in tumors larger than 1 mm The administration of P125A human endostatin in C3(1)/Tag females resulted in a significant delay in tumor onset, decreased tumor multiplicity and tumor burden and prolonged survival of the animals. Endostatin treatment did not reduce the number of preinvasive lesions, proliferation rates or apoptotic index, compared with controls. However, mRNA levels of a variety of proangiogenic factors (VEGF, VEGF receptors Flk‐1 and Flt‐1, angiopoietin‐2, Tie‐1, cadherin‐5 and PECAM) were significantly decreased in the endostatin‐treated group compared with controls. These results demonstrate that P125A endostatin inhibits the angiogenic switch during mammary gland adenocarcinoma tumor progression in the C3(1)/Tag transgenic model. © 2002 Wiley‐Liss, Inc.
Cyclosporin A enhances the apoptotic effects of N‐(4‐hydroxyphenyl)retinamide in breast cancer cells
Authors: Lim Soo‐Jeong , Simeone Ann‐Marie , Kim Chong‐Kook , Tari Ana M.
Published: August 2002

4HPR, an analogue of ATRA, effectively induces growth inhibition and apoptosis in breast cancer cell lines and animal models but is ineffective against advanced human breast tumors. Different compounds, including tamoxifen, are currently being tested to increase 4HPR efficacy in the clinic. Here, we report that cyclosporin A selectively increases the ability of 4HPR, but not ATRA, to induce growth inhibition and apoptosis in ER+ and ER− breast cancer cell lines. Increased apoptosis by the 4HPR and cyclosporin A combination was correlated with increased production of the free radical nitric oxide. Thus, the 4HPR and cyclosporin A combination may potentially be a novel therapeutic modality against breast tumors. © 2002 Wiley‐Liss, Inc.
Increased risk of grade IV neutropenia after administration of 5‐fluorouracil due to a dihydropyrimidine dehydrogenase deficiency: High prevalence of the IVS14+1g>a mutation
Authors: Van Kuilenburg André B.P. , Meinsma Rutger , Zoetekouw Lida , Van Gennip Albert H.
Published: August 2002

Dihydropyrimidine dehydrogenase (DPD) is the initial and rate‐limiting enzyme in the catabolism of 5‐fluorouracil (5‐FU), and it is suggested that patients with a partial deficiency of this enzyme are at risk of developing severe 5‐FU‐associated toxicity. We evaluated the importance of DPD deficiency, gender and the presence of the IVS14+1G>A mutation in the etiology of 5‐FU toxicity. In 61% of cases, decreased DPD activity could be detected in peripheral blood mononuclear cells. Furthermore, the number of females (65%) in the total group of patients appeared to be higher than the number of males (35%) (p = 0.03). Patients with partial DPD deficiency appeared to have a 3.4‐fold higher risk of developing grade IV neutropenia than patients with normal DPD activity. Analysis of the DPYD gene of patients suffering from grade IV neutropenia for the presence of the IVS14+1G>A mutation showed that 50% of the patients investigated were heterozygous or homozygous for the IVS14+1G>A mutation. Adopting a threshold level for DPD activity of 70% of that observed in the normal population, 14% of the population is prone to the development of severe 5‐FU‐associated toxicity. Below this threshold level, 90% of individuals heterozygous for a mutation in the DPYD gene can be identified. Considering the common use of 5‐FU in the treatment of cancer, the severe 5‐FU‐related toxicities in patients with low DPD activity and the apparently high prevalence of the IVS14+1G>A mutation, screening of patients at risk before administration of 5‐FU is warranted. © 2002 Wiley‐Liss, Inc.
Prognostic significance of cytokine modulation in non‐small cell lung cancer
Authors: Neuner A. , Schindel M. , Wildenberg U. , Muley T. , Lahm H. , Fischer J.R.
Published: August 2002

Increased production of immunosuppressive interleukin‐10 (IL‐10) by non‐small cell lung cancer (NSCLC) and increased serum IL‐10 concentrations in NSCLC‐patients have recently been correlated to reduced survival. We earlier demonstrated suppression of IL‐2 secretion in whole blood cell cultures of NSCLC‐patients. We now analyzed the influence of IL‐2 secretion on survival in NSCLC‐patients and the influence of IL‐10 on IL‐2 secretion. The correlation of the IL‐2 producing ability of whole blood cells in response to PHA in 90 NSCLC‐patients at the time of diagnosis to survival was calculated by Crit‐level, the Kaplan‐Meier method and the log‐rank test. With a cut‐off value of IL‐2 production of 1,100 pg/ml by whole blood cells the difference in survival was significant with ap‐value of 0.014. In the group with high and low IL‐2, median survival was 14.1 and 9.7 months, respectively. In the subgroup of 33 surgically‐treated patients the difference in survival was significant with ap‐value of 0.011. In 14 patients with surgical resection of the tumor and high IL‐2 at diagnosis and 19 patients with surgical resection, but low IL‐2 at diagnosis, median survival was 86.2 and 11.3 months, respectively. Secretion of IL‐2 in whole blood cell cultures from healthy individuals was inhibited in a dose‐dependent manner upon addition of IL‐10. Taken together, suppression of IL‐2 secretion has prognostic significance for survival of NSCLC‐patients and may be mediated by tumor‐derived IL‐10. © 2002 Wiley‐Liss, Inc.
BXD recombinant inbred mice represent a novel T cell–mediated immune response tumor model
Authors: Grizzle William E. , Mountz John D. , Yang Ping‐Ar , Xu Xin , Sun Sheher , Van Zant Gary E. , Williams Robert W. , Hsu Hui‐Chen , Zhang Huang‐Ge
Published: August 2002

To develop a better animal model for studying the effects of the host environment in neoplasia, we injected various genetically well‐characterized H‐2d RI strains of BXD mice with syngeneic breast cancer cells (TS/A) and monitored the growth of tumors over time. There was a marked difference in the growth of the implanted breast cancer cells among the 14 BXD RI strains, with 4 patterns of tumor development being observed: in type I, the implanted tumor cells grew rapidly in the first 2 weeks, necrosis of the tumors was observed and metastases to the intestinal lymph nodes and pancreas was observed, causing death; in type II, the implanted tumor cells grew slowly and attained a size after day 50 that required killing the animal, with tumor necrosis being rare and metastases absent; in type III, the implanted tumor cells grew initially but underwent a slow decline after 4 weeks; and in type IV, the implanted tumor cells failed to develop. Apoptosis of the implanted tumor cells was responsible for the regression of tumor nodules. The T‐cell immune response minimized tumor development in types III and IV since T‐cell depletion of the BXD RI mice resulted in aggressively growing tumors in these strains. © 2002 Wiley‐Liss, Inc.
Devaluation Expectations and the Stock Market: a new measure and an application to Mexico 1994/95
Authors: Becker Torbjörn , Gelos R. Gaston , Richards Anthony J.
Published: August 2002

This paper develops a market‐based measure of devaluation expectations derived from the relative stock market performance of companies with different exposures of current and future profits to exchange‐rate changes. The measure can be viewed as a complement to measures of devaluation expectations based on interest‐rate‐parity conditions, survey data or macroeconomic models. Some of the benefits of the measure are that data are available on a timely basis and that the stock market has traditionally been free of central bank intervention. As an illustration, we examine the Mexican devaluation of 1994. Contrary to what might have been expected given the alleged peso overvaluation, high‐net‐exporting firms outperformed the market beginning in late 1993. This pattern is, on the other hand, consistent with forward‐looking stock prices that assigned an increasing probability to a devaluation benefiting exporting firms. Copyright © 2002 John Wiley & Sons, Ltd.
Financial market integration in Europe: on the effects of EMU on stock markets
Authors: Fratzscher Marcel
Published: August 2002

This paper analyses the integration process of European equity markets since the 1980s. Its central focus is on the role that EMU, and specifically, changes in exchange rate volatility, has played in this process of financial integration. Building on an uncovered interest rate parity condition to measure financial integration, a trivariate GARCH model with time‐varying coefficients yields three key results: first, European equity markets have become highly integrated only since 1996. Second, the Euro area market has gained considerably in importance in world financial markets and has taken over from the USA as the dominant market in Europe. Third, the integration of European equity markets is in large part explained by the drive towards EMU, and in particular the elimination of exchange rate volatility and uncertainty in the process of monetary unification. Copyright © 2002 John Wiley & Sons, Ltd.
The determinants of birth intervals: a qualitative approach from Punjab, India
Authors: Huber Ulli S.
Published: August 2002

The determinants of birth intervals have been a focus of attention because of the strong relationship between birth intervals, mortality and fertility. This paper criticises the conventional hazard model approach to the determinants of birth intervals on the grounds of, first, the widespread assumption that birth intervals are planned and go according to plan, and secondly, a common failure to situate birth intervals within the social structures in which they take place. In‐depth interviews with four Punjabi couples about their birth interval related experiences are used to illustrate an alternative approach, which centres on an exploration of the roots of each action influencing birth intervals. This exploration takes into account that not all human actions are planned to maximise the actor's benefit, but that they can also be normative, habitual, or emotion‐driven; and it disentangles the two‐way relationship between birth interval related actions and social structures. Birth intervals are thought to be unlikely to develop according to a master plan because of their complexity, which stems from the considerable number of actions and actors involved in creating them. Copyright © 2002 John Wiley & Sons, Ltd.
Summarizing electronic discourse
Authors: Farrell Robert
Published: August 2002

The explosion of available information on the Internet has fueled the demand for automatic methods of text summarization. Existing approaches have primarily focused on abstracting documents such as news articles or technical papers. In this article, we examine how to create summaries of on‐line asynchronous communication, in particular, discussion groups. First, we provide background on the nature of discussions as informal communication, and then we give a short history of computer conferencing and discussion systems. We then explain our approach to the problem and a set of observations and experiments we have done, putting our work in the context of research on automatic text summarization. We then describe a hierarchical discourse summarization algorithm and its implementation in system called Interactive Discussion Summarizer (IDS). We close with discussion and conclusions. Copyright © 2002 John Wiley & Sons, Ltd.
Decadal variability of the Danube river flow in the lower basin and its relation with the North Atlantic Oscillation
Authors: Rîmbu Norel , Boroneanţ Constanţa , Buţă Carmen , Dima Mihai
Published: August 2002

The decadal variability (>5 years) of the Danube river flow in the lower basin and its connection with the North Atlantic Oscillation (NAO) is analysed for the period 1931–95. Associated linkages with precipitation (PP) in the European sector, global sea surface temperature (SST) and atmospheric circulation for the period 1931–81, and the 500 hPa geopotential heights (G500) over the Northern Hemisphere for the period 1948–95 are also investigated.

The results show that there is an out‐of‐phase relationship between the time series of the Danube river flow anomalies and the NAO index. The time series of a PP index, defined as the average of normalized precipitation anomalies over a large area including the Danube basin, presents a time evolution similar to that of the river flow anomalies.

The correlation maps between the river flow anomalies and global SST show coherent large‐scale patterns. High values of the Danube river flow are associated with a tripole‐like SST structure in the North Atlantic similar to that appearing during the negative phase of the NAO, and with negative SST anomalies in the central North Pacific and positive SST anomalies in the eastern and central tropical Pacific. Physically consistent sea level pressure and 500 hPa geopotential height are obtained. Copyright © 2002 Royal Meteorological Society.
Dependence between extreme sea surge, river flow and precipitation in eastern Britain
Authors: Svensson Cecilia , Jones David A.
Published: August 2002

Flooding in estuaries may be caused by both high river flows and by high sea levels. In order to investigate whether these tend to occur simultaneously in eastern Britain, the dependence between high sea surge (observed sea level minus predicted astronomical tide), river flow and precipitation was studied using a measure of dependence specially developed for extremal dependence. Extreme events were interpreted using meteorological maps. This new analysis found that the strongest flow–surge dependence occurs between river flow on the north shore of the Firth of Forth and sea surge at Aberdeen, Wick and Lerwick. In contrast to most other catchments in eastern Britain, the area to the north of the Firth of Forth is not sheltered from south‐westerly winds by any major topographical barrier. Therefore, precipitation from this direction may be orographically enhanced as it encounters the hills on the northern side of the firth, and high river flows may ensue. Events resulting in both high river flow and surge in the northern part of the study area were found to be caused by cyclones travelling north‐eastward to the north of Scotland. High surge events, only, were associated with similar storm tracks, but without much precipitation from the fronts. High river flows, only, were associated with rain‐bearing east–west‐directed fronts over northern Britain, with slow‐moving depressions located over or to the west of the British Isles where they are unable to generate a strong surge in the North Sea. The dependence between river flow and surge was found to be stronger during winter than summer, and a lagged analysis revealed that the dependence is strongest when flow and surge occur on the same day, but was also strong for lags of plus and minus 1 day. For precipitation, the dependence with both flow and surge is strongest when precipitation precedes them by 1 day. Copyright © 2002 Royal Meteorological Society.
The contribution of a discursive view to understanding and managing organizational change
Authors: Heracleous Loizos
Published: August 2002

Effective change management is not just about the ‘hard’ structural aspects of organizations; it requires an in‐depth appreciation of the cultural, human aspects of organizations, and taking actions based on this understanding.

Organizational discourse can provide access to this conceptual world of organizations and can also be used as an avenue for influencing it.

Recent empirical research is used to illustrate the above points.

Use of metaphor by change agents is then discussed as a prime example of how discourse can help to achieve effective organizational change.

Copyright © 2002 John Wiley & Sons, Ltd.
Enterprise resource planning systems and organizational change: transforming work organization?
Authors: Hall Richard
Published: August 2002

Enterprise Resource Planning Systems (ERPs) are computer‐based technologies that integrate data across an organization and impose standardized procedures on the input, use and dissemination of that data.

This paper argues that ERPs are an increasingly important source of organizational change with major implications for the organization and management of work.

ERPs are potentially associated with the following changes in the organization of work: downsizing and delayering of organizations; decentralizing responsibilities for various tasks while further concentrating control; increasing the range and depth of skills for some jobs while deskilling and routinizing the tasks inherent in other jobs; and the intensification of work in many jobs within the organization.

ERP implementations, therefore, need to be managed carefully.

Copyright © 2002 John Wiley & Sons, Ltd.
Changing the language of change: how new contexts and concepts are challenging the ways we think and talk about organizational change
Authors: Marshak Robert J.
Published: August 2002

This article proposes that our current terminology and conceptual language for organizational change make it difficult to address the range of changes confronting contemporary organizations.

Difficulties discussed include ambiguous and imprecise ways of talking about organizational change, changing organizational contexts that require new ways to think and talk about change, and dealing with implicit assumptions about change that may not be relevant in a world of continual change.

A matrix of change scenarios is presented and the term ‘morphing’ is introduced to describe continuous whole‐system change in hyperactive business environments.

Concepts, assumptions and metaphors associated with ‘altered consciousness’ and self‐organizing ‘complex adaptive systems’ are also discussed as alternative ways to think and talk about transformational change.

Implications discussed include the need to be specific and self‐reflective when thinking and talking about organizational change, and to rethink a possible over‐reliance on mechanistic, engineering or planned movement concepts, metaphors and word imagery.

Copyright © 2002 John Wiley & Sons, Ltd.
Building visitor attractions in peripheral areas—Can uniqueness overcome isolation to produce viability?
Authors: Prideaux Bruce
Published: August 2002

Attractions are a major component of the tourism industry and often exert considerable influence over individual travel priorities. In peripheral areas the uniqueness of attractions becomes an issue of greater significance than in the core, as visitors must allocate additional time and finances to travel greater distances to participate in the experiences on offer vis à vis competing attractions located nearer to the core. This paper considers a range of issues that affect the construction and operation of visitor attractions in the periphery. Issues that are of particular importance are location and access factors, the community, supporting tourism infrastructure and viability. As the isolation factor increases, the scale of the attraction must increase as must its uniqueness factor if it is to achieve and maintain viability. The significance of these factors is illustrated by considering the development of Burra as a heritage tourism attraction located in the near periphery of Adelaide, South Australia. Copyright © 2002 John Wiley & Sons, Ltd.