bluuebunny/crossref_metadata_2025 huggingface dataset:
APP knockout attenuates microglial activation and enhances neuron survival in substantia nigra compacta after axotomy
Authors: De Giorgio Lorraine A. , Shimizu Yoshinori , Chun Hong S. , Cho Byung‐Pil , Sugama Shuei , Joh Tong H. , Volpe Bruce T.
Published: August 2002

Focal microglial activation and progressive dopaminergic neurodegeneration in substantia nigra compacta (SNc) have characterized Parkinson's disease (PD). We have hypothesized that the microglial response may be provoked by molecular signals from chronically stressed SNc neurons. To test whether amyloid precursor protein (APP) could serve as such a signal, we evaluated microglial activation in SN after unilateral transection of the medial forebrain bundle (MFB) in mice either wild‐type (WT) or null (KO) for APP. WT and KO mice displayed comparable microglial response at the MFB transection site. In WT mice microglial activation was first apparent in the ipsilateral SN at 3 days postlesion (dpl), marked by morphological change and increased isolectin immunoreactivity. The microglial response intensified at 7 dpl and persisted in the medial nigra through 14 dpl. In contrast, in KO mice activated microglia appeared predominantly at 7 dpl, with little activation at 3 dpl and none at 14 dpl. Neuron number in affected WT SNc at 14 dpl was significantly reduced compared with loss in affected KO SNc. The delayed and limited local microglial activation and increased neuron survival in response to distal axotomy of SNc neurons in APP KO mice are consistent with the important role APP in neuronal stress responses in vivo. GLIA 38:174–178, 2002. © 2002 Wiley‐Liss, Inc.
Expression of β‐chemokines and chemokine receptors in human fetal astrocyte and microglial co‐cultures: Potential role of chemokines in the developing CNS
Authors: Rezaie P. , Trillo‐Pazos G. , Everall I.P. , Male D.K.
Published: August 2002

Chemokines play specific roles in directing the recruitment of leukocyte subsets into inflammatory foci within the central nervous system (CNS). The involvement of these cytokines as mediators of inflammation is widely accepted. Recently, it has become evident that cells of the CNS (astrocytes, microglia, and neurons) not only synthesize, but also respond functionally or chemotactically to chemokines. We previously reported developmental events associated with colonization of the human fetal CNS by mononuclear phagocytes (microglial precursors), which essentially takes place within the first two trimesters of life. As part of the array of signals driving colonization, we noted specific anatomical distribution of chemokines and chemokine receptors expressed during this period. In order to further characterize expression of these molecules, we have isolated and cultured material from human fetal CNS. We demonstrate that unstimulated subconfluent human fetal glial cultures express high levels of CCR2 and CXCR4 receptors in cytoplasmic vesicles. Type I astrocytes, and associated ameboid microglia in particular, express high levels of surface and cytoplasmic CXCR4. Of the chemokines tested (MIP‐1α, MIP‐1β, MCP‐1, MCP‐3, RANTES, SDF‐1, IL‐8, IP‐10), only MIP‐1α, detected specifically on microglia, was expressed both constitutively and consistently. Low variable levels of MCP‐1, MIP‐1α, and RANTES were also noted in unstimulated glial cultures. Recombinant human chemokines rhMCP‐1 and rhMIP‐1α also displayed proliferative effects on glial cultures at [10 ng/ml], but displayed variable effects on CCR2 levels on these cells. rhMCP‐1 specifically upregulated CCR2 expression on cultured glia at [50 ng/ml]. It is gradually becoming evident that chemokines are important in embryonic development. The observation that human fetal glial cells and their progenitors express specific receptors for chemokines and can be stimulated to produce MCP‐1, as well as proliferate in response to chemokines, supports a role for these cytokines as regulatory factors during development. GLIA 37:64–75, 2002. © 2002 Wiley‐Liss, Inc.
Improvement of cognitive functions after cobalamin/folate supplementation in elderly patients with dementia and elevated plasma homocysteine
Authors: Nilsson Karin , Gustafson Lars , Hultberg Björn
Published: August 2002

Objectives

To investigate the effect of cobalamin/folate supplementation on cognitive function in elderly patients with dementia.

Method

The cobalamin/folate status of the patients was evaluated by measuring plasma homocysteine, serum methylmalonic acid, serum cobalamin and blood folate. Thirty‐three patients were studied and repeatedly assessed with the Mini‐Mental State Examination (MMSE) and ‘A short cognitive performance test for assessing memory and attention’ (SKT) during vitamin substitution.

Results

Patients with mild–moderate dementia and elevated plasma homocysteine levels improved clinically with increased test scores after vitamin substitution, while severely demented patients and patients with normal plasma homocysteine levels did not improve clinically.

Conclusions

Plasma homocysteine may be the best marker for detecting treatable cobalamin/folate deficiency in patients with dementia. Copyright © 2001 John Wiley & Sons, Ltd.
Pharmacological treatment of depression in older primary care patients: the PROSPECT algorithm
Authors: Mulsant Benoit H. , Alexopoulos George S. , Reynolds Charles F. , Katz Ira R. , Abrams Robert , Oslin David , Schulberg Herbert C. ,   the PROSPECT Study Group
Published: August 2002

PROSPECT (Prevention of Suicide in Primary care Elderly–Collaborative Trial) is testing whether a trained clinician (the ‘health specialist’) can work in close collaboration with a primary care physician to implement a comprehensive depression management program and improve outcomes in older depressed patients. An algorithm guiding the selection and use of antidepressant medications has been developed to assist PROSPECT health specialists. This algorithm is presented and the rationale underlying the proposed treatment sequence is discussed. The PROSPECT algorithm builds upon existing guidelines after updating them and adapting them to the special circumstances of older primary care patients. Special attention has been paid to the tolerability and the target doses of the recommended antidepressant agents and to the duration of antidepressant trials. Patients who are unable to tolerate or do not respond to an antidepressant can be switched to another agent or be treated with interpersonal psychotherapy. Agents that produce only a partial response can be combined with other antidepressants or with interpersonal psychotherapy. Treatments for which empirical evidence exists are favored. However, treatments that are often poorly tolerated by elderly patients are given lower priority than treatments more likely to be tolerated. Similarly, trials that are simpler to implement in primary care are favored. Copyright © 2001 John Wiley & Sons, Ltd.
A system for the generation of curves on 3D brain images
Authors: Bartesaghi Alberto , Sapiro Guillermo
Published: August 2002

In this study, a computational optimal system for the generation of curves on triangulated surfaces representing 3D brains is described. The algorithm is based on optimally computing geodesics on the triangulated surfaces following Kimmel and Sethian ([1998]: Proc Natl Acad Sci 95:15). The system can be used to compute geodesic curves for accurate distance measurements as well as to detect sulci and gyri. These curves are defined based on local surface curvatures that are computed following a novel approach presented in this study. The corresponding software is available to the research community. Hum. Brain Mapping 14:1–15, 2001. © 2001 Wiley‐Liss, Inc.
Paradigms and research programmes: is it time to move from health care economics to health economics?
Authors: Edwards Rhiannon Tudor
Published: August 2002

As an applied subdiscipline of economics, health economics has flourished, defining itself as the study of how scarce health care resources may be used to meet our needs. This evolutionary pathway has led to health economists adopting a very ‘medical’ model of health, in which the predominant production function for health is health care. This paper sets out policy challenges to health economics which have arisen in light of growing recognition by governments of the socioeconomic determinants of health and their stated commitment to tackle inequalities in health. It reviews Thomas Kuhn's theory of paradigm shift and Imre Lakatos' theory of scientific research programmes in the natural sciences, favouring the latter as an explanation of the evolution of the subdiscipline of health economics. The paper brings together four recently published visions of the future of health economics—visions that are almost exclusively focused on the production, organization and distribution of health care. In contrast to these visions, in Lakatosian terms, this paper challenges the subdiscipline's core ‘positive heuristic’, i.e. the set of imperatives which determines how the research programme should unfold, how it may be defended, its scope and boundaries. This paper argues that health economics will need to evolve to embrace a more socioeconomic model of health and, to this end, offers for debate an expansion of Williams’ diagrammatic representation of the subdiscipline. It concludes by asking whether the magnitude and the magnetism of health care policy issues will continue to prove too strong to allow health economists, should they wish, to steer their research and educational programmes more directly towards ‘health’ rather than ‘health care’ as the relevant social want. Copyright © 2001 John Wiley & Sons, Ltd.
Measuring willingness‐to‐pay for risk reduction: an application of conjoint analysis
Authors: Telser Harry , Zweifel Peter
Published: August 2002

This study applies conjoint analysis (CA) to estimate the marginal willingness‐to‐pay (MWTP) of elderly individuals for a reduction of the risk of fracture of the femur. The good in question is a hypothetical hip protector which lowers the risk of a fracture by different amounts. Other attributes are ease of handling, wearing comfort, and out‐of‐pocket cost, which are traded off against risk reduction. In 500 face‐to‐face interviews, pensioners stated whether or not they would buy the product.

Results suggest that MWTP for wearing comfort exceeds that for risk reduction. Indeed, willingness‐to‐pay for the product as a whole is negative, indicating that it should not be included as a mandatory benefit in health insurance. Copyright © 2002 John Wiley & Sons, Ltd.
Preoperative assessment for and outcomes of mandibular conservation surgery
Authors: Werning John W. , Byers Robert M. , Novas Mark A. , Roberts Dianna
Published: August 2002

Introduction

The role of marginal mandibulectomy and other conservative resective procedures for patients with early cortical mandibular invasion from squamous carcinoma of the oral cavity remains poorly defined. The purpose of this retrospective study was to evaluate the efficacy of preoperative assessment for bone invasion and the outcomes of different mandibular resective procedures that preserve mandibular continuity.

Methods

The charts of 222 patients treated at the University of Texas M. D. Anderson Cancer Center between 1960 and 1990 were reviewed. All patients had a biopsy‐confirmed diagnosis of squamous carcinoma involving either the lower gingiva, floor of mouth, oral tongue, or retromolar trigone. All patients had a surgical resection that involved removing less than a segment of the mandible. Patient data were analyzed to determine the usefulness of preoperative assessment and outcomes of therapy.

Results

Clinical evaluation of mandibular bone invasion was more sensitive than radiologic evaluation, whereas radiologic assessment was more specific and had a higher reliability index. The overall local and regional recurrence and distant metastasis rates for all T stages were 14.4%, 18.0%, and 2.7%, respectively. Sixty‐nine point eight percent of all patients were without evidence of disease 2 years after treatment.

Conclusions

Mandibular conservation surgery is oncologically safe for patients with early mandibular invasion. Accurate preoperative assessment that combines clinical examination and radiographic evaluation is better than either modality alone, but clinical judgment is still necessary for proper patient selection. © 2001 John Wiley & Sons, Inc. Head Neck 23: 1024–1030, 2001.
Prognostic significance of serum p53 protein and p53 antibody in patients with surgical treatment for head and neck squamous cell carcinoma
Authors: Chow Vivian , Yuen Anthony Po Wing , Lam King Yin , Ho Wai Kuen , Wei William Ignace
Published: August 2002

Objectives

This study aims at investigating the prognostic values of serum p53 protein and anti‐p53 antibody in patients undergoing surgical treatment for head and neck squamous cell carcinoma (HNSCC).

Methods

Serum p53 protein and anti‐p53 antibody concentrations were determined by an enzyme‐linked immunosorbent assay (ELISA) in 75 patients with HNSCC and 28 healthy controls. In 28 patients, formalin‐fixed tumor tissues were also available for immunohistochemical staining by an anti‐p53 DO7 monoclonal antibody. The results were correlated with the clinicopathologic parameters.

Results

The mean preoperative serum concentration of p53 protein in patients with HNSCC was significantly higher than healthy controls (59.45 pg/mL vs 16.4 pg/mL, p = .007). Preoperative serum p53 antibody was present in 23 (31%) patients and was present in one healthy control. Eighteen (62%) tumor tissues showed p53 overexpression by immunohistochemistry. The presence of serum anti‐p53 antibody before operation was associated with a significantly higher incidence (65%) of nodal metastasis compared with 27% nodal metastasis in patients with absence of serum anti‐p53 antibody (p = .002).

Conclusion

Preoperative serum p53 antibody was a significant prognostic factor for nodal metastasis of HNSCC. © 2001 John Wiley & Sons, Inc. Head Neck 23: 286–291, 2001.
Hyperexcitability and epilepsy associated with disruption of the mouse neuronal‐specific K–Cl cotransporter gene
Authors: Woo Nam‐Sik , Lu Jianming , England Roger , McClellan Robert , Dufour Samuel , Mount David B. , Deutch Ariel Y. , Lovinger David M. , Delpire Eric
Published: August 2002

Four genes encode electroneutral, Na+‐independent, K–Cl cotransporters. KCC2, is exclusively expressed in neurons where it is thought to drive intracellular Cl− to low concentrations and shift the reversal potential for Cl− conductances such as GABAA or glycine receptor channels, thus participating in the postnatal development of inhibitory mechanisms in the brain. Indeed, expression of the cotransporter is low at birth and increases postnatally, at a time when the intracellular Cl− concentration in neurons decreases and γ‐aminobutyric acid switches its effect from excitatory to inhibitory. To assert the significance of KCC2 in neuronal function, we disrupted the mouse gene encoding this neuronal‐specific K–Cl cotransporter. We demonstrate that animals deficient in KCC2 exhibit frequent generalized seizures and die shortly after birth. We also show upregulation of Fos, the product of the immediate early gene c‐fos, and the significant loss of parvalbumin‐positive interneurons, both indicative of brain injury. The regions most affected are the hippocampus and temporal and entorhinal cortices. Extracellular field potential measurements in the CA1 hippocampus exhibited hyperexcitability. Application of picrotoxin, a blocker of the GABAA receptor, further increased hyperexcitability in homozygous hippocampal sections. Pharmacological treatment of pups showed that diazepam relieved the seizures while phenytoin prevented them between postnatal ages P4–P12. Finally, we demonstrate that adult heterozygote animals show increased susceptibility for epileptic seizure and increased resistance to the anticonvulsant effect of propofol. Taken together, these results indicate that KCC2 plays an important role in controlling CNS excitability during both postnatal development and adult life. Hippocampus 2002;12:258–268. © 2002 Wiley‐Liss, Inc.
Tuberculosis in blood and marrow transplant recipients
Authors: Yuen K. Y. , Woo P. C. Y.
Published: August 2002

Although one third of the world's population is infected with tuberculosis (TB), TB in blood and marrow transplant (BMT) recipients is relatively less well studied, as the incidence of TB is relatively low in developed countries with BMT units. Since the report of the first two cases in 1983, 52 cases of TB complicating BMT have been reported in the English literature from BMT centers in ten different countries. Not unexpectedly, the two largest series were reported from areas with a high incidence of TB in the general population, with about 45 cases per 105 inhabitants per year in Spain and about 100 cases per 105 inhabitants per year in Hong Kong respectively. The overall frequency of occurrence of TB in BMT recipients was 0.4% (52 cases among 13 881 BMT recipients), with a male:female ratio of 11:9 and median age of 33 (range 7‒57). The incidence of TB in the general population is a major predictor of a higher frequency of occurrence in BMT recipients. Moreover, allogeneic transplantation, graft‒versus‒host disease, and total body irradiation were found to be risk factors associated with TB. Among the 48 cases in whom the time of manifestation were reported, only one case manifested during the neutropenic period (day 11). On the other hand, 11 cases (23%) manifest after engraftment but before day 100, and 36 (75%) manifest after day 100. The most important aspect towards making the diagnosis is a high index of suspicion, as TB occurred in relatively low frequencies especially in developed countries, and the clinical patterns usually mimic other more common infectious and non‒infectious complications after BMT. As the incidence of drug resistant TB is increasing, we prefer to treat our patients for at least one year (as compared with six months in immunocompetent hosts) with four drugs in the first six months and two or three drugs for another six months. In those patients who could not tolerate oral medication, we used an intravenous regimen of rifampicin, ciprofloxacin, and amikacin until oral therapy could be instituted. The absence of relapse after termination of treatment in our patients suggested that secondary prophylaxis would not be necessary as long as immune function has been restored. With the rising incidence of TB in countries that previously enjoyed a very low prevalence of TB, attributed to the growing population of HIV‒infected subjects with TB, and the changing patterns of population migration, it is important to bear a high index of suspicion of Mycobacterium tuberculosis as a pathogen in BMT recipients. Copyright © 2001 John Wiley & Sons, Ltd.
Heat transfer for flow boiling of water and critical heat flux in a half‐heated round tube under low‐pressure conditions
Authors: Kobayashi Toshiyuki , Mishima Kaichiro
Published: August 2002

Heat transfer for flow boiling of water and critical heat flux (CHF) experiments in a half‐circumferentially heated round tube under low‐pressure conditions were carried out. To clarify the flow patterns in the heated section, experiments in the round tube under the same conditions were also carried out, and their results were compared. The experiments were conducted with atmospheric‐pressure water in test sections with inner diameter D = 6 mm, heated length L = 360 mm, inlet water subcooling ΔTin = 80 K, and mass velocity G from 0 to 2000 kg/(m2·s) for the half‐circumferentially heated round tube and from 0 to 7000 kg/(m2·s) for the full‐circumferentially heated tube. The experimental data demonstrated that the wall temperature near the outlet of the half‐circumferentially heated tube remained almost the same until CHF. It was found that burnout occurred when the flow regime changed from churn flow to annular flow, and the liquid film on the heated wall dried out although liquid film on the unheated wall remained. © 2002 Wiley Periodicals, Inc. Heat Trans Asian Res, 31(3): 149–164, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/htj.10022
Using numerical modelling to address hydrologic forest management issues in British Columbia
Authors: Alila Younes , Beckers Jos
Published: August 2002

This paper outlines how long‐term statistical–deterministic physically based hydrologic modelling utilizing data from experimental watersheds in British Columbia (BC) can be used to fill knowledge gaps related to forest management in the BC Forest Practices Code, and discusses data and modelling issues that need to be considered in this context. Developing hydrologic model applications for these experimental watersheds will further provide insight regarding priorities for future data collection and will also advance our understanding of capabilities and limitations of physically based hydrologic models in addressing watershed management concerns in BC. Experience and expertise obtained in this fashion is a prerequisite for successful use of these hydrologic models in evaluating site‐specific forest management issues at catchments with fewer data resources. Copyright © 2001 John Wiley & Sons, Ltd.
Density‐dependent surface water–groundwater interaction and nutrient discharge in the Swan–Canning Estuary
Authors: Smith Anthony J. , Turner Jeffrey V.
Published: August 2002

Salinity in the Swan–Canning Estuary, Western Australia, varies seasonally from freshwater conditions in winter up to the salinity of seawater in summer. Field observations show that the resulting seasonal density contrasts between the estuary and the adjacent fresh groundwater system are sufficient to drive mixed‐convection cells that give rise to circulation of river water in the aquifer. In this study, we examine the role of steady density‐driven convection as a mechanism that contributes to the exchange of dissolved nutrients, particularly ammonium, between the Swan–Canning Estuary and the local groundwater system. We present results from two‐dimensional (section) and three‐dimensional density‐coupled flow and mass transport modelling, in comparison with Glover's abrupt‐interface solution for saltwater intrusion. The modelling is focused on developing an understanding of the physical processes that influence the long‐term or mean convective behaviour of groundwater beneath the estuary. It is shown that the convective stability depends fundamentally on the interplay between two factors: (1) the downward destabilizing buoyancy effect of density contrasts between the estuary and aquifer; and (2) the upward stabilizing influence of regional groundwater discharge. The structure of convection cells beneath the estuary and recirculation rates of estuary water within the groundwater system are shown to be related to a flow‐modified Rayleigh number that depends critically on the aquifer anisotropy and estuary meander pattern. The recirculation of estuary water by these mechanisms is responsible for transport of high concentrations of ammonium, observed in pore fluids in the estuary bed sediments, into groundwater and its eventual return to the estuary. Copyright © 2001 John Wiley & Sons, Ltd.
Dysregulation of phosphatidylinositol 3‐kinase and downstream effectors in human breast cancer
Authors: Salh Baljinder , Marotta Anthony , Wagey Ravenska , Sayed Mohamed , Pelech Steven
Published: August 2002

Phosphatidylinositol 3‐kinase (PI3‐K) is a growth factor‐activated transforming lipid (and protein) kinase, involved in cell motility and invasion, that has multiple effectors. Relatively little is known about its expression and enzymatic activity in human breast cancer. Since growth factor receptors are amplified in breast cancer, and the tumor suppressor PTEN may be mutated in human breast cancer, it was hypothesized that PI3‐K and its downstream effectors would be activated in this disease. In 11 resected tumors analyzed for expression of this kinase, a mean 3‐fold increase in protein expression was observed over the corresponding adjacent control tissue. Using an in vitro lipid kinase assay of the immunoprecipitated PI3‐K protein, a greater than 2‐fold increase in activation was observed. These changes were observed in the absence of an activation of either protein kinase B (PKB, akt1) or p70 S6 kinase (p70 S6K). However, p21‐activated kinase (Pak), p38 mitogen‐activated protein kinase (p38 MAPK) and mitogen‐activated protein kinase‐activated protein kinase 2 (MAPKAPK 2) were all overexpressed and demonstrated increased enzyme activity. It may be concluded that aberrant mitogenic signaling in human breast cancer in vivo involves Pak, p38 MAPK and MAPKAPK2 downstream of PI3‐K, but neither of PKB or p70 S6K. It is proposed that this pathway may serve as a useful targeting nexus for investigation of small molecule inhibitors in human breast cancer. © 2001 Wiley‐Liss, Inc.
Food‐derived polyphenols inhibit pancreatic cancer growth through mitochondrial cytochrome C release and apoptosis
Authors: Mouria Michelle , Gukovskaya Anna S. , Jung Yoon , Buechler Peter , Hines Oscar J. , Reber Howard A. , Pandol Stephen J.
Published: August 2002

There is increasing evidence that food‐derived polyphenols have a beneficial effect for cancers. Our purpose was to determine the effect and mechanism of action of these compounds on pancreatic cancer. We measured effects of quercetin on pancreatic cancer in a nude mouse model. We also investigated the effects of quercetin, rutin, trans‐resveratrol and genistein on apoptosis and underlying signaling in pancreatic carcinoma cells in vitro. Quercetin decreased primary tumor growth, increased apoptosis and prevented metastasis in a model of pancreatic cancer. In vitro quercetin and trans‐resveratrol, but not rutin, markedly enhanced apoptosis, causing mitochondrial depolarization and cytochrome c release followed by caspase‐3 activation. In addition, the effect of a combination of quercetin and trans‐resveratrol on mitochondrial cytochrome c release and caspase‐3 activity was greater than the expected additive response. The inhibition of mitochondrial permeability transition prevented cytochrome c release, caspase‐3 activation and apoptosis caused by polyphenols. Nuclear factor‐κB activity was inhibited by quercetin and trans‐resveratrol, but not genistein, indicating that this transcription factor is not the only mediator of the polyphenols' effects on apoptosis. The results suggest that food‐derived polyphenols inhibit pancreatic cancer growth and prevent metastasis by inducing mitochondrial dysfunction, resulting in cytochrome c release, caspase activation and apoptosis. © 2002 Wiley‐Liss, Inc.
Diagnostic accuracy of stereotactic large‐core needle biopsy for nonpalpable breast disease: Results of a multicenter prospective study with 95% surgical confirmation
Authors: Verkooijen Helena M.
Published: August 2002

Stereotactic large‐core needle biopsy is increasingly applied for the diagnosis of nonpalpable breast disease. Our study examines whether this minimally invasive technique is sufficiently accurate to replace surgical breast biopsy. In a prospective multicenter study, 973 consecutive women with 1,029 nonpalpable breast lesions were offered stereotactic 14‐gauge needle biopsy. If the needle biopsy yielded breast cancer, the patient was offered therapeutic surgery. Surgical biopsy was proposed in cases of needle biopsies without malignancy. An expert panel reviewed all discrepancies in histologic diagnosis between the needle biopsy and open biopsy. Forty‐five patients withdrew from participation and 113 (11%) planned needle biopsy procedures were cancelled. Of the 871 successful biopsy procedures, 95% were confirmed surgically. In 13 cases (1.5%), insufficient material was obtained for histologic assessment. Fifty‐five percent of the needle biopsies were diagnosed as malignant (290 invasive cancers, 190 ductal carcinoma in situ). Thirteen of the 322 lesions (4%, 95% CI 2–7%) with a benign needle biopsy diagnosis contained malignancy after surgery. Six of the 26 (23%, 95% CI 9–44%) lesions with a high‐risk diagnosis (atypical ductal or lobular hyperplasia or lobular carcinoma in situ) were diagnosed as malignant after surgery. Five of the 30 lesions containing normal breast tissue held malignancy (17%, 95% CI 6–35%). Guidelines for the management of different categories of needle biopsy diagnoses were made. Application of these guidelines to the present findings resulted in sensitivity and specificity rates of 97% (95% CI 95–98%) and 99% (95% CI 97–100%), respectively. Stereotactic large‐core needle biopsy is an accurate diagnostic instrument for nonpalpable breast disease. It may safely replace needle localised open‐breast biopsy provided that high‐risk and normal breast tissue diagnoses are followed by needle or open‐breast biopsy. © 2002 Wiley‐Liss, Inc.
A validity and reliability study of assessment and screening for sustained withdrawal reaction in infancy: The Alarm Distress Baby scale
Authors: Guedeney Antoine , Fermanian Jacques
Published: August 2002

Sustained withdrawal behavior in infancy is an important alarm signal to draw attention to both organic and relationship disorders. A withdrawal scale, the Alarm Distress Baby scale (ADBB), for infants between 2 and 24 months of age was built. This article describes the construction of the scale and the assessment of its psychometric properties. The ADBB has good content validity, based on the advice of seven experts. The scale has good criterion validity: first, as a measure of the infant's withdrawal reaction, with a very good correlation between nurse and pediatrician on the ADBB (rs = 0.84), and second, as a screening procedure for detecting the developmental risk of the infant. The cutoff score of 5 with a sensitivity of 0.82 and a specificity of 0.78 was determined to be optimal for screening purposes. The scale has good construct validity, with good convergent validity with both the Spitz (1951) and the Herzog & Rathbun (1982) lists of symptoms of infant depression (rs = 0.61 and 0.60, respectively). Exploratory factor analysis showed two different factors, consistent with the scale's construct. Reliability was satisfactory with good internal consistency for both subscales (the Cronbach α = 0.80 for the first subscale and 0.79 for the second) and for the global scale (α = 0.83). The test‐retest procedure showed good stability over time (rs = 0.90 and 0.84 for the two different raters). The scale could be used in different clinical settings, provided a sufficient level of social stimulation is given to the infant in a relatively brief period of time. The scale can be used by nurses and psychologists or by medical doctors after a short period of training.

 © 2001 Michigan Association for Infant Mental Health.
Decision‐making capabilities of a hybrid system applied to the auditor's going‐concern assessment
Authors: Lenard Mary Jane , Alam Pervaiz , Booth David , Madey Gregory
Published: August 2002

The purpose of this study is to evaluate a hybrid system as a decision support model to assist with the auditor's going‐concern assessment. The going‐concern assessment is often an unstructured decision that involves the use of both qualitative and quantitative information. An expert system that predicts the going‐concern decision has been developed in consultation with partners at three of the Big Five accounting firms. This system is combined with a statistical model that predicts bankruptcy, as a component of the auditor's decision, to form a hybrid system. The hybrid system, because it combines the use of quantitative and qualitative information, has the potential for better prediction accuracy than either the expert system or statistical model predicting separately. In addition, testing of the system provides some insight into the characteristics of firms that experience problems, but do not necessarily receive a going‐concern modification. Further investigation into those firms that have problems could reveal factors that may be incorporated into decision support systems for auditors, in order to improve accuracy and reliability of these decision tools. © 2001 John Wiley & Sons, Ltd.
Cluster analysis using a validated self‐organizing method: cases of problem identification
Authors: Wang Shouhong
Published: August 2002

Kohonen's self‐organizing feature maps (SOFM) are commonly used in cluster analysis for problem solving. However, given a set of sample data, the cluster analysis results obtained by using the standard SOFM method can vary depending on the setting of the parameters of the SOFM. To validate the cluster analysis results, information in addition to the data for the SOFM is required. This paper reports practical cases of cluster analysis using SOFM in conjunction with a measure of validation. In these cases, multivariate data of survey were used to identify problems through validated SOFM cluster analyses. Copyright © 2001 John Wiley & Sons, Ltd.
The demand for M3 in the euro area
Authors: Coenen G. , Vega J.‐L.
Published: August 2002

In this paper, an empirically stable money demand model for M3 in the euro area is constructed. Starting with a multivariate system, three cointegrating relationships with economic content are found: (i) the spread between the long‐term and the short‐term nominal interest rates, (ii) the long‐term real interest rate, and (iii) a long‐run demand for broad money M3. There is evidence that the determinants of M3 money demand are weakly exogenous with respect to the long‐run parameters. Hence, following a general‐to‐specific modelling approach, a parsimonious conditional error‐correction model for M3 money demand is derived which can be interpreted economically. For the conditional model, long‐run and short‐run parameter stability is extensively tested and not rejected. Copyright © 2001 John Wiley & Sons, Ltd.
Chronic toxicity/oncogenicity study of styrene in cd‐1 mice by inhalation exposure for 104 weeks
Authors: Cruzan George , Cushman Janette R. , Andrews Larry S. , Granville Geoffrey C. , Johnson Keith A. , Bevan Christopher , Hardy Colin J. , Coombs Derek W. , Mullins Pamela A. , Brown W. Ray
Published: August 2002

Groups of 70 male and 70 female Charles River CD‐1 mice were exposed whole body to styrene vapor at 0, 20, 40, 80 or 160 ppm 6 h per day 5 days per week for 98 weeks (females) or 104 weeks (males). The mice were observed daily; body weights, food and water consumption were measured periodically, a battery of hematological and clinical pathology examinations were conducted at weeks 13, 26, 52, 78 and 98 (females)/104 (males). Ten mice of each gender per group were pre‐selected for necropsy after 52 and 78 weeks of exposure and the survivors of the remaining 50 of each gender per group were necropsied after 98 or 104 weeks. An extensive set of organs from the control and high‐exposure mice were examined histopathologically, whereas target organs, gross lesions and all masses were examined in all other groups.

Styrene had no effect on survival in males. Two high‐dose females died (acute liver toxicity) during the first 2 weeks; the remaining exposed females had a slightly higher survival than control mice. Levels of styrene and styrene oxide (SO) in the blood at the end of a 6 h exposure during week 74 were proportional to exposure concentration, except that at 20 ppm the SO level was below the limit of detection. There were no changes of toxicological significance in hematology, clinical chemistry, urinalysis or organ weights. Mice exposed to 80 or 160 ppm gained slightly less weight than the controls. Styrene‐related non‐neoplastic histopathological changes were found only in the nasal passages and lungs. In the nasal passages of males and females at all exposure concentrations, the changes included respiratory metaplasia of the olfactory epithelium with changes in the underlying Bowman's gland; the severity increased with styrene concentration and duration of exposure. Loss of olfactory nerve fibers was seen in mice exposed to 40, 80 or 160 ppm. In the lungs, there was decreased eosinophilia of Clara cells in the terminal bronchioles and bronchiolar epithelial hyperplasia extending into alveolar ducts. Increased tumor incidence occurred only in the lung. The incidence of bronchioloalveolar adenomas was significantly increased in males exposed to 40, 80 or 160 ppm and in females exposed to 20, 40 and 160 ppm. The increase was seen only after 24 months. In females exposed to 160 ppm, the incidence of bronchiolo‐alveolar carcinomas after 24 months was significantly greater than in the controls. No difference in lung tumors between control and styrene‐exposed mice was seen in the intensity or degree of immunostaining, the location of tumors relative to bronchioles or histological type (papillary, solid or mixed). It appears that styrene induces an increase in the number of lung tumors seen spontaneously in CD‐1 mice. Copyright © 2001 John Wiley & Sons, Ltd.
Selective vulnerability to kainate‐induced oxidative damage in different rat brain regions
Authors: Candelario‐Jalil Eduardo , Al‐Dalain Saied Mohammed , Castillo Rubén , Martínez Gregorio , León Fernández Olga Sonia
Published: August 2002

Some markers of oxidative injury were measured in different rat brain areas (hippocampus, cerebral cortex, striatum, hypothalamus, amygdala/piriform cortex and cerebellum) after the systemic administration of an excitotoxic dose of kainic acid (KA, 9 mg kg−1 i.p.) at two different sampling times (24 and 48 h). Kainic acid was able to lower markedly (P < 0.05) the glutathione (GSH) levels in hippocampus, cerebellum and amygdala/piriform cortex (maximal reduction at 24 h). In a similar way, lipid peroxidation, as assessed by malonaldehyde and 4‐hydroxyalkenal levels, significantly increased (P < 0.05) in hippocampus, cerebellum and amygdala/piriform cortex mainly at 24 h after KA. In addition, hippocampal superoxide dismutase (SOD) activity decreased significantly (P < 0.05) with respect to basal levels by 24 h after KA application. On the other hand, brain areas such as hypothalamus, striatum and cerebral cortex seem to be less susceptible to KA excitotoxicity. According to these findings, the pattern of oxidative injury induced by systemically administered KA seems to be highly region‐specific. Further, our results have shown that a lower antioxidant status (GSH and SOD) seems not to play an important role in the selective vulnerability of certain brain regions because it correlates poorly with increases in markers of oxidative damage. Copyright © 2001 John Wiley & Sons, Ltd.
Biocompatibility and in vivo gentamicin release from bioactive sol–gel glass implants
Authors: Meseguer‐Olmo L. , Ros‐Nicolás M. J. , Clavel‐Sainz M. , Vicente‐Ortega V. , Alcaraz‐Baños M. , Lax‐Pérez A. , Arcos D. , Ragel C. V. , Vallet‐Regí M.
Published: August 2002

Biomaterial pieces, with suitable osteogenic properties for use in the treatment of bone defects and the capability to avoid bone infections, have been synthesized. These materials are composed exclusively of gentamicin sulfate and bioactive SiO2‐CaO‐P2O5 sol–gel glass (previously synthesized). Implant processing was achieved by uniaxial and isostatic pressure of the components mixture. After implanting the pieces into rabbit femur, we studied (i) the antibiotic release, determining the concentration in proximal and distal bone, liver, kidney, and lung as a function of time; and (ii) the bone growth resulting from the glass reactivity in the biologic environment. The results indicate that the implants are good carriers for local gentamicin release in the osseous tissue, exhibiting excellent biocompatibility and bone integration. Moreover, these implants are able to promote bone growth during their resorption process. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 61: 458–465, 2002
Adhesion behavior of monocytes, macrophages, and foreign body giant cells on poly (N‐isopropylacrylamide) temperature‐responsive surfaces
Authors: Collier Terry O. , Anderson James M. , Kikuchi Akihiko , Okano Teruo
Published: August 2002

Monocyte and macrophage adhesion and foreign body giant cell (FBGC) formation has been observed on surfaces with a wide range of properties. In this study we have utilized novel, temperature‐responsive surfaces (TRS) with dynamic surface properties to investigate inflammatory cell adhesion behavior. With temperature changes, grafted chains of poly‐N‐isopropylacrylamide pass through their lower critical solution temperature (LCST) and can either extend (hydrate), creating a hydrophilic surface at 20°C, or contract (dehydrate), creating a hydrophobic surface at 37°C. Isolated human monocytes and monocyte‐derived macrophages were able to adhere, spread, and form FBGC on the hydrophobic surface. Decreasing the temperature below the lower critical solution temperature induced a change in the surface wettability, creating a hydrophilic surface, that induced a differential detachment of adherent cells that decreased with time, ranging from 98% after 2 h of culture to 30% at day 10. These detached cells remained viable, and were recultured onto TCPS for 3, 7, and 10 days. These novel surfaces allow investigation of the adhesive behavior of adherent inflammatory cells in a temporal manner, and the effects of surface conformation and wettability changes on cell adhesion and detachment. © 2001 Wiley Periodicals, Inc. J Biomed Mater Res 59: 136–143, 2002
Hydroxylapatite with substituted magnesium, zinc, cadmium, and yttrium. II. Mechanisms of osteoblast adhesion
Authors: Webster Thomas J. , Ergun Celaletdin , Doremus Robert H. , Bizios Rena
Published: August 2002

The present in vitro study investigated osteoblast adhesion on hydroxylapatite (HA) doped with either cadmium (Cd), zinc (Zn), magnesium (Mg), or yttrium (Y). Compared with any other dopant tested in the present study, osteoblast adhesion was significantly (p < 0.05) greater on HA doped with Y after 4 h; in addition, osteoblast adhesion increased with concentration (2–7 mol%) of Y in HA. The findings that HA doped with greater amounts of Y adsorbed higher concentrations of calcium and, subsequently, of vitronectin and collagen (proteins known to mediate osteoblast adhesion), but not of albumin, laminin, and fibronectin, may explain the observed enhanced adhesion of osteoblasts on these substrates. Interactions (i.e., adsorption and configuration/bioactivity) of vitronectin and collagen may have been promoted by increased porosity of doped HA. Through doping with Y, the present study provided the first evidence that HA can be synthesized and processed with improved cytocompatibility properties for osteoblast adhesion, and thus offered essential information for the design of novel proactive bioceramics. Proactive bioceramics which elicit specific, timely, and desired responses from surrounding cells and tissues are necessary for improving bonding of orthopaedic/dental implants to juxtaposed bone; such osseointegration will, undoubtedly, enhance implant efficacy. © 2001 Wiley Periodicals, Inc. J Biomed Mater Res 59: 312–317, 2002
A comparison of 60, 70, and 90 kDa stress protein expression in normal rat NRK‐52 and human HK‐2 kidney cell lines following in vitro exposure to arsenite and cadmium alone or in combination
Authors: Madden Emily F. , Akkerman Miriam , Fowler Bruce A.
Published: August 2002

Arsenite and cadmium are two potent nephrotoxicants and common Superfund site elements. These elements are included among the stress protein inducers, but information regarding relationships between toxicity produced by combinations of these agents to the stress protein response is lacking. In this study, the immortalized cell lines normal rat kidney NRK‐52E and human kidney HK‐2 were exposed in vitro to arsenite (As3+), cadmium (Cd2+), or to equimolar As3+ plus Cd2+ mixture combinations for 3 and 5 h over a concentration range of 0.1–100 μM. After a 12‐h recovery period, cultured cells were then evaluated for expression of the 60, 70, and 90 kDa major stress protein families. Results indicated that expression of stress proteins varied depending on the species of kidney cells exposed, the exposure concentrations, and the length of exposure to each element on an individual basis and for combined mixtures. For the HK‐2 kidney cell line, increased levels of the 70 kDa stress protein was observed for single and combined element exposures whereas there was no change or a decrease of stress proteins 60 and 90 kDa. Increased 70 kDa expression was observed for 10‐μM doses of single elements and for a lower dose of 1 μM of the As plus Cd mixture at 3‐ and 5‐h exposures. NRK‐52 kidney cells exposed to equivalent doses of As3+ and Cd2+ alone or in combination showed increased levels of all stress proteins 60, 70, and 90 kDa. This increase was seen for 10 μM of the As plus Cd mixture at 3 h whereas for single element exposures, increased stress protein levels were generally observed for the 100‐μM doses. At 5 h‐ exposure, 60 and 90 kDa levels increased for 10 μM of Cd2+ and 60 kDa levels increased for 1 μM of As3+. However, exposures to 10 μM of the As plus Cd mixture decreased 60 kDa protein expression to control levels at 5 h. For both kidney cell lines, there was a decrease in the stress protein expression levels for all three stress protein families for 100‐μM doses of the mixture combination for 3‐ and 5‐h exposures. These data indicate a dose‐ and combination‐related correlation between depression of the stress protein response and the onset of overt cellular toxicity and/or cell death. The threshold for these changes was cell line specific. © 2002 Wiley Periodicals, Inc. J Biochem Mol Toxicol 16:24–32, 2002; DOI 10.1002/jbt.10015
Mammalian DNA methyltransferases show different subnuclear distributions
Authors: Margot Jean B. , Cardoso M. Cristina , Leonhardt Heinrich
Published: August 2002

In mammalian cells, DNA methylation patterns are precisely maintained after DNA replication with defined changes occurring during development. The major DNA methyltransferase (Dnmt1) is associated with nuclear replication sites during S‐phase, which is consistent with a role in maintenance methylation. The subcellular distribution of the recently discovered de novo DNA methyltransferases, Dnmt3a and Dnmt3b, was investigated by immunofluorescence and by epitope tagging. We now show that both Dnmt3a and Dnmt3b are distributed throughout the nucleoplasm but are not associated with nuclear DNA replication sites during S‐phase. These results suggest that de novo methylation by Dnmt3a and Dnmt3b occurs independently of the replication process and might involve an alternative mechanism for accessing the target DNA. The different subcellular distribution of mammalian DNA methyltransferases might thus contribute to the regulation of DNA methylation. J. Cell. Biochem. 83: 373–379, 2001. © 2001 Wiley‐Liss, Inc.
A fast pairwise evaluation of molecular surface area
Authors: Vasilyev Vladislav , Purisima Enrico O.
Published: August 2002

A fast and general analytical approach was developed for the calculation of the approximate van der Waals and solvent‐accessible surface areas. The method is based on three basic ideas: the use of the Lorentz transformation formula, a rigid‐geometry approximation, and a single fitting parameter that can be refitted on the fly during a simulation. The Lorentz transformation equation is used for the summation of the areas of an atom buried by its neighboring contacting atoms, and implies that a sum of the buried pairwise areas cannot be larger than the surface area of the isolated spherical atom itself. In a rigid‐geometry approximation we numerically calculate and keep constant the surface of each atom buried by the atoms involved in 1‐2 and 1‐3 interactions. Only the contributions from the nonbonded atoms (1‐4 and higher interactions) are considered in terms of the pairwise approximation. The accuracy and speed of the method is competitive with other pairwise algorithms. A major strength of the method is the ease of parametrization. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 737–745, 2002