bluuebunny/crossref_metadata_2025 huggingface dataset:
Destruction of chemical warfare agents VX and soman by α‐nucleophiles as oxidizing agents
Authors: Cassagne Thierry , Cristau Henri‐Jean , Delmas Gérard , Desgranges Michel , Lion Claude , Magnaud Gilbert , Torreilles Éliane , Virieux David
Published: August 2002

Reactions of O‐ethyl S‐(2‐diisopropyl‐amino)ethyl methylphosphonothiolate, VX 1, were investigated with five oxidizing agents. In all the cases, the formation of the VX N‐oxide 7 was observed prior to the subsequent oxidation and hydrolysis into the nontoxic O‐ethyl methylphosphonate 2. Magnesium monoperoxyphthalate (MMPP) is probably one of the most active reagents to achieve the complete detoxification of VX 1. The decontamination using MMPP was also extended with success to soman 13, a G‐type agent. © 2001 John Wiley & Sons, Inc. Heteroatom Chem 12:485–490, 2001
The distribution problem in economic evaluation: income and the valuation of costs and consequences of health care programmes
Authors: Donaldson Cam , Birch Stephen , Gafni Amiram
Published: August 2002

To date, a common view in the health economics literature is that the applicability of cost–benefit analysis (CBA) is limited, due to the distribution problem which underlies its main method of valuation (e.g. willingness to pay). One view is that cost effectiveness analysis (CEA) overcomes these problems. We show that the same distributional concerns apply to non‐monetary valuations of health consequences, to measurement of costs and to the decision rules of CEA. Hence adopting CEA over CBA cannot be justified on the basis of ‘avoiding’ distributional considerations. The implications of our results are discussed, including alternative strategies for the use of ‘income‐based’ research findings in social decision‐making. Copyright © 2001 John Wiley & Sons, Ltd.
Do Medicare HMOs still reduce health services use after controlling for selection bias?
Authors: Mello Michelle M. , Stearns Sally C. , Norton Edward C.
Published: August 2002

This study models the relationship between Medicare beneficiary decisions to join Medicare HMOs and subsequent health services utilization. The relationship between health plan choice and utilization is thought to be endogenous because of favorable selection into HMOs. Previous studies found significantly lower inpatient utilization among Medicare HMO enrollees than among nonenrollees, but lacked strong controls for selection bias. Thus, a firm conclusion could not be drawn as to whether the observed differences were attributable to the HMO practice setting or to baseline differences in the illness profiles of the two groups studied. The present study uses simultaneous equations methods, including discrete factor estimation, to test the effect of Medicare HMOs on utilization when strong controls for selection bias are imposed. The model was run on a panel of 1993–1996 data from the Medicare Current Beneficiary Survey, supplemented with linked data on Medicare HMO characteristics and area supply characteristics. The study found that even when favorable selection is controlled for, Medicare HMOs significantly reduce both the probability of hospitalization and the number of inpatient days used by those who are hospitalized. Medicare HMOs do not, however, appear to reduce the use of physician services. Copyright © 2002 John Wiley & Sons, Ltd.
Management of advanced mandibular osteoradionecrosis with free flap reconstruction
Authors: Chang David W. , Oh Hee‐kyun , Robb Geoffrey L. , Miller Michael J.
Published: August 2002

Background

The purpose of this study was to assess the effectiveness of free tissue transfer for treatment of advanced mandibular osteoradionecrosis (ORN) in head and neck cancer patients.

Methods

We reviewed 29 patients who were treated for advanced mandibular ORN by radical resection and reconstruction with free flaps at our institution. All patients had either failed to respond to conservative treatment, including hyperbaric oxygen therapy and debridement or had pathological fracture due to ORN.

Results

Twenty‐four vascularized bone (17 fibula, five iliac, and two scapula), four rectus abdominis myocutaneous, and one radial forearm fasciocutaneous free flaps were used. The complications occurred in 6 of 29 patients (21%). A total of four flaps (14%) were lost. The mean follow‐up was 2 years 9 months. All patients had complete resolution of ORN symptoms. No evidence of ORN recurrence was observed in any patient.

Conclusion

For advanced osteoradionecrosis of the mandible, radical resection followed by reconstruction using free flap provides a reliable means of obtaining good wound healing with acceptable aesthetic and functional results. © 2001 John Wiley & Sons, Inc. Head Neck 23: 830–835, 2001.
Cd8+/vβ5.1+ large granular lymphocyte leukemia associated with autoimmune cytopenias, rheumatoid arthritis and vascular mammary skin lesions: successful response to 2‐deoxycoformycin.
Authors: Granjo E. , Lima M. , Correia T. , Lisboa C. , Magalhães C. , Cunha N. , Teixeira MA. , Queirós ML. , Candeias J. , Matutes E.
Published: August 2002

We report a case of CD8+/Vβ5.1+ T‐cell large granular lymphocyte leukemia (T‐LGL leukemia) presenting with mild lymphocytosis, severe autoimmune neutropenia, thrombocytopenia, polyarthritis and recurrent infections with a chronic disease course. Immunophenotyping showed an expansion of CD3+/TCRαβ+/CD8+bright/CD11c+/CD57−/CD56− large granular lymphocytes with expression of the TCR‐Vβ5.1 family. Southern blot analysis revealed a clonal rearrangement of the TCR β‐chain gene. Hematopoietic growth factors, high dose intravenous immunoglobulin and corticosteroids were of limited therapeutic benefit to correct the cytopenias. During the disease course, the patient developed a severe cutaneous leg ulcer and bilateral vascular mammary skin lesions. Treatment with 2‐deoxycoformycin resulted in both clinical and hematological complete responses, including the resolution of vascular skin lesions. Combined immuno‐staining with relevant T‐cell associated and anti‐TCR‐Vβ monoclonal antibodies proved to be a sensitive method to assess the therapeutic effect of 2‐deoxycoformicin and to evaluate the residual disease. Copyright © 2002 John Wiley & Sons, Ltd.
A study of heat transfer in high‐performance hydrogen bell‐type annealing furnaces
Authors: Zuo Yi , Wu Wen‐fei , Zhang Xin‐xin , Lin Lin , Xiang Shun‐hua , Liu Tie‐shu , Niu Long‐ying , Huang Xia‐lan
Published: August 2002

The mechanisms of heat transfer in high‐performance hydrogen bell‐type annealing furnaces are discussed in this paper. It examines two important parameters, the convective heat transfer coefficient and the equivalent radial thermal conductivity, which have large effects on the overall heat transfer in the furnace. The calculated annealing curves are in good agreement with experimental data. © 2001 Scripta Technica, Heat Trans Asian Res, 30(8): 615–623, 2001
Simulation of heat transfer in the cool storage unit of a liquid–air energy storage system
Authors: Araki Hidefumi , Nakabaru Mitsugu , Chino Kooichi
Published: August 2002

An energy storage system that stores energy in the form of liquid air was studied. In this system, the cool storage unit was the most important unit. From the viewpoint of safety and economy, it was most promising to store the cold energy as the sensitive heat of a solid such as pebbles or concrete. A simulator was developed to predict temperature variations of the solid cool storage unit. The simulator calculated unsteady heat transfer between a supercritical gas flow and the solid material. Comparison of calculated and experimental results showed that the temperature variation of the metal cool storage medium was accurate within 11%. The calculated results showed for the concrete cool storage unit that a smaller quantity of medium was required with a smaller pitch of the tube. The minimum quantity of concrete calculated at the smallest pitch was three times that of concrete, which was simply estimated from the heat capacity of concrete and air. The volume required for concrete cool storage was less than 1/100 that of reservoirs for a pumped‐hydro power station having a vertical drop of 500 m. © 2002 Wiley Periodicals, Inc. Heat Trans Asian Res, 31(4): 284–296, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/htj.10035
Prediction of groundwater characteristics in forested and harvested basins during spring snowmelt using a topographic index
Authors: Buttle J. M. , Hazlett P. W. , Murray C. D. , Creed I. F , Jeffries D. S. , Semkin R.
Published: August 2002

Consistent relationships between groundwater conditions and topographic properties in small drainage basins would assist the study and modelling of basin hydrology and hydrochemistry. Hydrochemical simulation using topographically based models would benefit in particular from the linkage of groundwater residence times to topographic indices, such as the ln(a / tan β) index of Beven and Kirkby. Hypothesized associations between this index and groundwater characteristics were tested during the spring 2000 snowmelt in two sub‐basins in the Turkey Lakes Watershed near Sault Ste Marie, ON. One sub‐basin is in mature hardwood forest, and the other was clearcut in the fall of 1997. Piezometric surface elevations were monitored in each sub‐basin throughout the melt, and the topographic index value for each piezometer was determined. The δ18O signatures of input water and groundwater were also measured. Mean groundwater residence times were obtained using the exponential system response function, which generally produced good fits to the observed groundwater δ18O time series in both sub‐basins. There were significant contrasts in groundwater conditions between the sub‐basins. The forested sub‐basin exhibited higher and more temporally variable piezometric surface elevations and a greater contrast between δ18O signatures and water residence times in shallow versus deeper groundwater relative to the harvested sub‐basin. Patterns of groundwater residence times in the sub‐basins were supported by pre‐harvest groundwater chemistry; however, data from the two sub‐basins largely failed to support the hypothesized relationships between groundwater conditions and topographic index values. Methodological limitations that may have precluded a more rigorous test of the hypotheses are reviewed, and the potential for using groundwater residence times to evaluate the impacts of forest harvesting on basin hydrochemistry is briefly discussed. Copyright © 2001 John Wiley & Sons, Ltd.
Mothers' attachment representations and choice of infant care: center care vs. home
Authors: Koren‐Karie Nina
Published: August 2002

In the debate concerning the effects of day care on infant development, insufficient attention has been paid to the potential relationship between pre‐existing emotional differences among mothers and the type of care they choose for their infants. To shed light on this issue, this study examines the attachment representations of mothers who choose day‐care centres as opposed to mothers who choose to remain at home with their infants. Participants were 76 primiparous mothers. Mothers' attachment classifications were assessed by the Adult Attachment Interview [AAI; Main M, Kaplan N, Cassidy J. 1985. Security in infancy, childhood, and adulthood: a move to the level of representation. In Growing Points of Attachment Theory and Research. Monograph of the Society for Research in Child Development, 50, (1–2, serial no. 209), Bretherton I, Waters E (eds); 66–104]. Results indicate that more Day‐care than Home‐Care mothers are classified as insecurely attached. These results highlight the contribution of maternal emotional characteristics to the effects of diverse child care arrangements on infant development. Copyright © 2001 John Wiley & Sons, Ltd.
Dietary factors and gastric cancer in Korea: A case‐control study
Authors: Kim Hyun Ja , Chang Woong Ki , Kim Mi Kyung , Lee Sang Sun , Choi Bo Youl
Published: August 2002

To assess gastric cancer (GC) risk in relation to dietary intake in Korea, a case‐control study was performed. Trained dietitians interviewed 136 patients diagnosed with GC, and the same number of controls were selected by matching sex, age and hospital. A significant decrease in GC risk was observed with increased intake of Baiechu kimchi (prepared with salted Chinese cabbage and red pepper, etc.), Baiechu kimchi‐stew, garlic, mushroom and soybean milk. On the contrary, a significant increase in the risk of GC was observed with increased intake of cooked rice with bean, charcoal grilled beef, pollack soup, Kkakduki (a kind of kimchi prepared with salted radish and red pepper, etc.), Dongchimi (a kind of kimchi prepared with radish and a large quantity of salt water) and cooked spinach. In food groups, increased intake of soybean products was associated with decreased risk of GC. Intake of citrus fruits rather than total fruits was shown to have a protective effect on the risk of GC, but was not significant. In this study, intake of total vegetables was shown to have a protective effect, whereas high nitrate‐containing vegetables increased the risk of GC. In conclusion, our study suggests that the risk of GC decreased with high consumption of fresh vegetables and fruits, whereas high consumption of foods rich in nitrate and carcinogenic substances produced during the cooking process increased the risk of GC. © 2001 Wiley‐Liss, Inc.
Impact of BCRP/MXR, MRP1 and MDR1/P‐Glycoprotein on thermoresistant variants of atypical and classical multidrug resistant cancer cells
Authors: Stein Ulrike , Lage Hermann , Jordan Andreas , Walther Wolfgang , Bates Susan E. , Litman Thomas , Hohenberger Peter , Dietel Manfred
Published: August 2002

The impact of the ABC transporters breast cancer resistance protein/mitoxantrone resistance associated transporter (BCRP/MXR), multidrug resistance‐associated protein 1 (MRP1) and multidrug resistance gene‐1/P‐glycoprotein (MDR1/PGP) on the multidrug resistance (MDR) phenotype in chemoresistance and thermoresistance was investigated in the parental human gastric carcinoma cell line EPG85‐257P, the atypical MDR subline EPG85‐257RNOV, the classical MDR subline EPG85‐257RDB and their thermoresistant counterparts EPG85‐257P‐TR, EPG85‐257RNOV‐TR and EPG85‐257RDB‐TR. Within the atypical MDR subline EPG85‐257RNOV expression of BCRP/MXR and of MRP1 were clearly enhanced (vs. parental and classical MDR lines). MDR1/PGP expression was distinctly elevated in the classical MDR subline EPG85‐257RDB (vs. parental and atypical MDR sublines). In all thermoresistant counterparts basal expression of BCRP/MXR, MRP1 and MDR1/PGP was increased relative to thermosensitive sublines. Although it could be shown that the overexpressed ABC transporters were functionally active, however, no decreased drug accumulations of doxorubicin, mitoxantrone and rhodamine 123 were observed. Thus, expression of BCRP/MXR, MRP1 and MDR1/PGP was found to be dependent on the appropriate type of chemoresistance; correlating with a classical or atypical MDR phenotype. Within the thermoresistant variants, however, the increase in ABC transporter expression did obviously not influence the MDR phenotype. © 2001 Wiley‐Liss, Inc.
Cigarette smoking and subsequent risk of lung cancer by histologic type in middle‐aged Japanese men and women: The JPHC study
Authors: Sobue Tomotaka , Yamamoto Seiichiro , Hara Megumi , Sasazuki Shizuka , Sasaki Satoshi , Tsugane Shoichiro ,   for the JPHC Study Group
Published: August 2002

In order to update the findings of relative risk associated with cigarette smoking for lung cancer by histologic type in Japan, the data from a population‐based cohort study of 91,738 men and women were analyzed. During 1990–1999, 422 lung cancer incident cases were identified. The relative risk for all incident cases associated with current smokers versus non‐smokers was 4.5 [95% confidence interval (CI): 3.0–6.8] and 4.2 (95% CI: 2.4–7.2), for men and women, respectively. When divided by histologic type, relative risk for squamous cell carcinoma and small cell carcinoma was 12.7 (95% CI: 4.7–34.7) and 17.5 (95% CI: 4.9–62.1), while for adenocarcinoma it was 2.8 (95% CI: 1.6–4.9) and 2.0 (95% CI: 0.8–5.0) for men and women, respectively. We confirmed that the lung cancer risk in men rose with increasing cigarette smoking, especially the duration of smoking among current smokers and decreased after the cessation of smoking among former smokers. Unlike the US or European countries, the relative risk did not increase in this updated study, compared with previous studies in 1960s to 1990s in Japan either for all incident cases or for specific histologic types and the magnitude of relative risks was substantially lower than that observed in the US or European countries, especially for adenocarcinoma. © 2002 Wiley‐Liss, Inc.
Rat Muc4 (sialomucin complex) reduces binding of anti‐ErbB2 antibodies to tumor cell surfaces, a potential mechanism for herceptin resistance
Authors: Price‐Schiavi Shari A. , Jepson Scott , Li Peter , Arango Maria , Rudland Philip S. , Yee Lisa , Carraway Kermit L.
Published: August 2002

Muc4 (also called sialomucin complex), the rat homolog of human MUC4, is a heterodimeric glycoprotein complex that consists of a peripheral O‐glycosylated mucin subunit, ASGP‐1, tightly but noncovalently linked to a N‐glycosylated transmembrane subunit, ASGP‐2. The complex is expressed in a number of normal, vulnerable epithelial tissues, including mammary gland, uterus, colon, cornea and trachea. Muc4/SMC is also overexpressed or aberrantly expressed on a number of human tumors including breast tumors. Overexpression of Muc4/SMC has been shown to block cell‐cell and cell‐matrix interactions, protect tumor cells from immune surveillance and promote metastasis. In addition, as a ligand for ErbB2, Muc4/SMC can potentiate phosphorylation of ErbB2 and potentially alter signals generated from this receptor. Using A375 human melanoma cells and MCF7 human breast adenocarcinoma cells stably transfected with tetracycline regulatable Muc4, we have investigated whether overexpression of Muc4/SMC can repress antibody binding to cell surface‐expressed ErbB2. Overexpression of Muc4/SMC does not affect the level of ErbB2 expression in either cell line, but it does reduce binding of a number of anti‐ErbB2 antibodies, including Herceptin. Interestingly, overexpression of ErbB2 does not block binding of other unrelated antibodies of the same isotype, suggesting that the reduction in ErbB2 antibody binding is due to complex formation of Muc4/SMC and ErbB2. Furthermore, capping of Muc4/SMC with anti‐Muc4/SMC antibodies reduces antibody binding to ErbB2 instead of increasing binding, again suggesting that reduced antibody binding to ErbB2 is due to steric hindrance from complex formation of Muc4/SMC and ErbB2. Thus, overexpression of Muc4/SMC on tumor cells may have both prognostic and therapeutic relevance. © 2002 Wiley‐Liss, Inc.
Towards a new map of European migration
Authors: King Russell
Published: August 2002

Students of European migration have been hampered by the legacy of those established forms of migration which have been historically most important – settler migrations from Europe to the Americas, guest‐worker migrations from the Mediterranean Basin to Northern Europe, and refugee migrations after the World Wars. We need to appreciate that many of the key questions that were asked to frame our understanding of the functioning of migration now have a very different array of answers from the largely economic ones which shaped our earlier analyses. Now, new mobility strategies are deployed to achieve economic and, importantly, non‐economic objectives. In the new global and European map of migration, the old dichotomies of migration study – internal versus international, forced versus voluntary, temporary versus permanent, legal versus illegal – blur as both the motivations and modalities of migration become much more diverse. In offering an overview of the new typologies and geographies of international migration in Europe, this paper will be less a rigorous cartography than a qualitative exploration of a changing typology including migrations of crisis, independent female migration, migration of skilled and professional people, student migration, retirement migration and hybrid tourism–migration. These relatively new forms of migration derive from new motivations (the retreat from labour migrations linked to production), new space–time flexibilities, globalisation forces, and migrations of consumption and personal self‐realisation. More than ever, this multiplex nature of human migration and spatial mobility demands an interdisciplinary approach, enriched wherever possible by comparative studies. Copyright © 2002 John Wiley & Sons, Ltd.
Prenatal alcohol exposure and infant negative affect as precursors of depressive features in children
Authors: O'Connor Mary J.
Published: August 2002

This study examined the continuity of negative temperamental variations from infancy to early childhood. Also examined was the association of prenatal alcohol exposure with negative affect in infancy and with depressive features in early childhood. Participants were 41 6‐year‐old children who were followed longitudinally from 1 year of age. Infant negative affect was observed and behaviorally assessed at 1 year, and child depressive symptoms were measured at 6 years using a self‐report questionnaire. Results revealed continuity between infant negative affect and early childhood depressive symptoms. In addition, prenatal alcohol exposure appeared to be a significant risk factor in the development of depressive features through both its direct association with child outcome and its indirect effect on infant negative affect. Children with higher levels of prenatal alcohol exposure, who exhibited higher levels of negative affect at 1 year, reported more depressive symptoms at 6 years. This effect was observed primarily in girls. Results suggest one mechanism by which children exposed to alcohol in utero might be predisposed to display higher levels of negative emotionality in infancy placing them at greater risk for depression in early childhood. Continuity of negative affect and depressive symptoms in prenatally exposed youngsters suggests that interventions could begin in infancy and could be targeted specifically at negative child behaviors.  © 2001 Michigan Association for Infant Mental Health.
Relation‐based intervention with at‐risk mothers: Outcome in the second year of life
Authors: Heinicke Christoph M. , Fineman Neira R. , Ponce Victoria A. , Guthrie Donald
Published: August 2002

It has been shown that the UCLA home visiting/mother–infant group intervention made a significant positive impact during the child's first 2 years of life on two indices of the mother's support and on three areas of mother–child and child development: (1) The mother's responsiveness to the needs of her child and the related development of his or her security of attachment; (2) the mother's encouragement of her child's autonomy and the related development of his or her autonomy; and (3) the mother's encouragement of her child's task involvement and the related development of his or her task orientation. By child age 2 years, the mothers experiencing the intervention, in comparison with those that did not, also used verbally persuasive as opposed to coercive intrusive methods of control and their children responded more positively to these controls. Mothers who did not experience the help of the intervention had significantly more difficulty controlling their child if it was a boy as opposed to a girl. They used the least appropriate methods of control, and the boys responded more negatively to these controls.

The nature of the development of the mother's use of appropriate controls and the child's response to that control was elucidated by determining on the total sample where 12‐month antecedents influenced the indices of control either independently of or in interaction with the intervention status. The child's endurance in the test situation was an independent predictor of mother‐appropriate control and the child's positive response to that control, while the absence of maternal intrusiveness further enhanced the impact of the intervention on that control. ©2001 Michigan Association for Infant Mental Health.
Sediment transport applications in irrigation canals
Authors: Depeweg Herman , Méndez V Néstor
Published: August 2002

Sediment transport in irrigation canals is an important issue in the design and operation of irrigation systems. Frequently observed problems in irrigation systems are, for example, clogging of turnouts and reduction of the conveyance capacity of canals by siltation, and instability of side slopes and of structures due to erosion. Each year large investments are required to maintain or to rehabilitate these systems and to keep them in an acceptable condition for irrigation purposes.

Irrigation canals are generally designed based on the assumption of uniform and steady flow of water and sediments. However, the flow is predominantly non‐uniform, due to time‐dependent discharges and constant water levels at regulation and division points. A strong relationship exists between the sediment transport and flow conditions.

The aim of this article is to present some new developments in the behaviour of sediment and associated sediment transport in irrigation canals under changing flow conditions, as well as the deposition and/or entrainment rate in time and place for various flow conditions and sediment inputs. This article will discuss an approach to compute sediment transport in irrigation canals under non‐uniform flow conditions. The sediment transport has been analysed for the flow conditions that prevail in irrigation canals. The Ackers‐White and Brownlie equations are recommended to compute the sediment transport under equilibrium conditions for prismatic canal cross‐sections. For non‐equilibrium conditions, a numerical solution of Galappatti's depth‐integrated model is applied. Copyright © 2002 John Wiley & Sons, Ltd.
Water at any price? Issues and options in charging for irrigation water1
Authors: Perry Chris
Published: August 2002

Shortage of water and inadequate funding for maintenance of irrigation works have focused attention on the potential for water charges to generate financial resources, and reduce demand for water through volume‐based charges. Examples from other utilities, and from the domestic/industrial sectors of water supply, suggest the approach could be effective.

However, in many developing countries, the facilities required for measured and controlled delivery, which are both essential for volume‐related charges, are not in place and their introduction would require a massive investment in physical, legal and administrative infrastructure.

To be effective in curtailing demand, the price of water must be significant, but the price structures and levels that are within the politically feasible and acceptable range are usually too low to have a real impact on demand, much less to actually bring supply and demand into balance. Similarly, the present cost of water is too low to induce significant technical innovation or investments that could reduce consumption.

Moreover, while water supplied is a proper measure of service in domestic and industrial uses, in irrigation, and especially as the water resource itself becomes constrained, water consumption is the appropriate measure for water accounting, and this is exceptionally difficult to define.

An alternative approach to coping with shortage would focus on assigning volumes to specific uses – and effectively rationing water where demand exceeds supply – has a number of potential benefits including simplicity, transparency and the potential to tailor allocations specifically to hydrological situations. Copyright © 2001 John Wiley & Sons Ltd.
Enhancing the predictive validity of Frog Embryo Teratogenesis Assay—Xenopus (FETAX)
Authors: Fort Douglas J. , Paul Robbin R.
Published: August 2002

Frog Embryo Teratogenesis Assay—Xenopus (FETAX) is a 4‐day, alternative developmental toxicity assay designed to pre‐screen chemicals and environmental mixtures. An approach used in the scoring of FETAX results, which focuses on the determination of characteristic abnormalities induced by a given test material, was used to evaluate results from previous validation efforts. Characteristic abnormalities are induced specifically by exposure to a given test material and are determined by the relationship between concentration and the response induced and the change in severity of response. Use of this approach eliminates non‐specific effects that alter numerical endpoints, reduces intralaboratory variability, reduces the number of equivocal test results (gray area), helps to determine specific syndromes associated with teratogen exposure and, in some instances, increases the predictability of FETAX. In an effort to evaluate this approach, a 12‐compound validation study that produced a relatively high degree of equivocal FETAX results was re‐evaluated using the characteristic malformation criteria. Data were evaluated for repeatability, predictability and variability. Results from this study indicated that this scoring approach increased repeatability, test endpoint precision and predictability. Copyright © 2002 John Wiley & Sons, Ltd.
Biocompatibility studies on biodegradable polyester‐based composites of human osteoblasts: A preliminary screening
Authors: Calandrelli L. , Immirzi B. , Malinconico M. , Orsello G. , Volpe M. G. , Ragione F. Della , Zappia V. , Oliva A.
Published: August 2002

A series of biodegradable composites with natural hydroxyapatite, designed for possible use in orthopedics applications, were preliminarily screened for biocompatibility by employing primary cultures of human osteoblasts in a direct contact method. The cells were seeded at low density onto the materials under investigation and allowed to grow for 2 weeks. They then were analyzed for morphology, proliferation, viability, alkaline phosphatase activity (AP), osteocalcin (OC) production, and extracellular matrix mineralization. The results showed that all materials have good biocompatibility. Cell viability tests demonstrated that in all cases the values were comparable to the control, and the addition of hydroxyapatite always resulted in an enhancement of performance with respect to the plain polymer. AP and OC analysis confirmed that all composites allowed the expression of phenotypic markers. Scanning electron microscopy provided direct evidence of intense cell adhesion and proliferation on the tested materials. © 2001 Wiley Periodicals, Inc. J Biomed Mater Res 59: 611–617, 2002
Characterization of melt‐derived 45S5 and sol‐gel–derived 58S bioactive glasses
Authors: Sepulveda Pilar , Jones Julian R. , Hench Larry L.
Published: August 2002

The ability of bioactive glasses to form a bond to living bone and also to stimulate bone‐cell proliferation depends on the chemical composition and on the surface texture of the glasses. In this work, the differences in physical properties between the melt‐derived 45S5 and sol‐gel–derived 58S Bioglass® powders of various particle‐size ranges were studied. The powders were characterized for particle‐size distribution by laser spectrometry, for specific surface area and porosity by nitrogen sorption analysis, and for morphological features by scanning electron microscopy. Melt‐derived 45S5 powders exhibited a low‐porosity texture with surface area in the range 0.15–2.7 m2/g. In contrast, the sol‐gel–derived powders exhibited a highly mesoporous texture, with surface area in the range of 126.5–164.7 m2/g and a large fraction of 6–9 nm pore sizes. These differences in texture, as well as variations in chemical composition, account for significant changes in the resorption and in vivo responses. © 2001 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 58: 734–740, 2001
In vivo evaluation of a new sealant material on a rat lung air leak model
Authors: Kobayashi Hisatoshi , Sekine Takashi , Nakamura Tatsuo , Shimizu Yasuhiko
Published: August 2002

The ability of an albumin‐based hydrogel sealant (ABHS) to prevent air leakage through the suture line after pulmonary surgery was evaluated by comparison with that of a fibrin glue (FG). As an air‐leak model, a rat lung was used in which a standard incision was made and the burst pressure for ABHS and FG was measured. The average burst pressures at time 0 for the FG and ABHS groups were 30.8±15.2 and 77.5 ±19.1 mmHg, respectively. At Day 3, the value of ABHS (76.3 ± 15.8 mmHg) was still significantly higher (P<0.05) than that of FG (60.0 ± 21.9 mmHg). At Day 7, no statistical difference was observed between the FG group(71.2 ± 18.6 mmHg) and the ABHS group(88.8 ± 11.7 mmHg). Histological examination of the incision at Day 14 revealed that neither sealant was not visible at the incision site, and there was no evidence of adverse tissue reaction. It was concluded that ABHS had good sealing properties and is an alternative to FG for air leakage treatment in pulmonary surgery. © 2001 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 58: 658–665, 2001
Novel hydroxyapatite ceramics with an interconnective porous structure exhibit superior osteoconduction in vivo
Authors: Tamai Noriyuki , Myoui Akira , Tomita Tetsuya , Nakase Takanobu , Tanaka Junzo , Ochi Takahiro , Yoshikawa Hideki
Published: August 2002

Calcium hydroxyapatite ceramics (CHA) are nontoxic materials, provoke little reaction from tissues, and by virtue of these properties represent a good starting point for creating bone substitutes. Although several porous CHAs have been used clinically, there have been few reports that CHA is fully replaced by newly formed bone, which may be due to its structure and the limited connectivity between pores. We recently developed a fully interconnected porous CHA (IP‐CHA) by adopting a “foam‐gel” technique. Structural analysis by scanning electron microscopy revealed that IP‐CHA had spherical pores of uniform size that were interconnected by window‐like holes. The surface of the wall structure was smooth, and hydroxyapatite particles were bound tightly to one another. Most of the interpore connections of IP‐CHA ranged from 10 to 80 μm in diameter (average, 40 μm). When the cylindrical IP‐CHA (diameter, 6 mm; height, 15 mm) was implanted into a rabbit femoral condyle, bone, and bone marrow with abundant vessels formed deep in the pores through the interpore connections. Within a period of 6 weeks, new bone had formed and penetrated to a distance of 3 mm from the surface of the IP‐CHA implant. Furthermore, a compression test at 9 weeks revealed that the implanted IP‐CHA steadily increased in strength to more than double the value of the initial test. These results indicate that the IP‐CHA may have clinical utility as a superior bone substitute. © 2001 Wiley Periodicals, Inc. J Biomed Mater Res 59: 110–117, 2002
Albumin adsorption onto pyrolytic carbon: A molecular mechanics approach
Authors: Mantero Sara , Piuri Daniela , Montevecchi Franco M. , Vesentini Simone , Ganazzoli Fabio , Raffaini Giuseppina
Published: August 2002

A number of implants of cardiac valve prosthesis, vascular prosthesis, and coronary stents present a pyrolytic carbon interface to blood. Plasma protein adsorption is essential for the hemocompatibility of the implanted devices. This work quantitatively evaluates the molecular interaction force between a biomaterial surface (pyrolytic carbon) and plasma protein (albumin) binding sites through a simplified molecular model of the interface consisting of (i) multioriented graphite microcrystallites; (ii) selected fragments of albumin; and (iii) a water environment. A number of simplifying assumptions were made in the calculation: the albumin molecule was divided into hydrophobic and hydrophilic subunits (helices); an idealized clean, nonoxidized polycrystalline graphite surface was assumed to approximate the surface of pyrolytic carbon. The interaction forces between albumin helices and pyrolytic carbon surfaces are evaluated from potential energy data. These forces are decomposed into a normal and a tangential component. The first one is calculated using a docking procedure (F⊥tot MAX = 4.16 × 10−20 N). The second one (F‖), calculated by mean of geometric models estimating the energy variation associated with the protein sliding on the material surface, varies within the range ±9.62 × 10−21 N. The molecular simulations were performed using the commercial software package Hyperchem 5.0 (Hyperchem, Hypercube, Canada). © 2001 Wiley Periodicals, Inc. J Biomed Mater Res 59: 329–339, 2002
Osseointegration of hydroxyapatite‐coated and noncoated Ti6Al4V implants in the presence of local infection: A comparative histomorphometrical study in rabbits
Authors: Oosterbos C. J. M. , Vogely H. Ch. , Nijhof M. W. , Fleer A. , Verbout A. J. , Tonino A. J. , Dhert W. J. A.
Published: August 2002

A study was designed to investigate the osseointegration of titanium implants, either noncoated or coated with hydroxyapatite (HA), into rabbit tibiae in the presence of local infection compared with osseointegration in the absence of local infection. HA‐coated or noncoated Ti cylinders were implanted into both tibiae of 32 rabbits (New Zealand Whites). Before implantation the left tibia was contaminated with different quantities of Staphylococcus aureus (102–105 CFU). Four weeks after surgery the tibiae were explanted and prepared for microbiological and histomorphometrical examination. Histomorphometrical data, as a representation of implant fixation, were obtained by measuring the percentage of bone around the implants (within a radius of 1 mm from the outer diameter of the implants) and the percentage of the circumference of the implant that was in direct contact with bone. Histomorphometry revealed, in particular for the HA implants, a relationship between the inoculum concentration and/or the presence or absence of infection with the bone contact at the distal implant side. This confirms a relationship between peri‐implant infection and bone contact or remodeling. HA‐coated implants developed, in the presence of bacteria, more easily a more severe infection than noncoated Ti implants, and we show in the present study that local infection will influence histomorphometrical parameters (bone‐implant contact) that determine implant fixation. Precautions to prevent contamination (asepsis) and/or infection (perioperative antibiotics) are even more important for the highly biocompatible HA‐coated implant. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 60: 339–347, 2002; DOI 10.1002/jbm.1288
Differences in the nuclear chromatin among various stages of the life cycle of Trypanosoma cruzi
Authors: Spadiliero Barbara , Sánchez Fredi , Slezynger Thelma C. , Henríquez Diana A.
Published: August 2002

Trypanosoma cruzi is the etiological agent of Chagas. Although the nuclear chromatin of this parasite is organized in the form of nucleosome filaments, its chromatin is physically and enzymatically fragile, and no condensation into chromosomes occurs during mitosis. All previous investigations have been carried out with epimastigote form in its proliferate stage. It is not known whether these differences in chromatin structure are also found in the non‐proliferate stationary epimastigote forms and in tissue derived trypomastigotes. Our results confirm that chromatin of logarithmic epimastigotes presents limited compaction when increasing salt concentrations from 1 to 100 mM NaCl, and no 30‐nm fibers were formed. Contrary to these results, non‐proliferative forms of the parasites showed a pattern of compactation similar to that observed in rat liver chromatin, where solenoids of 30‐nm fibers are formed at 100‐mM NaCl. In accordance with these results, digestion of the nuclear chromatin with DNase I revealed that the chromatin of logarithmic phase epimastigotes was more accesible to the enzyme. We conclude from these results that structural differences in the chromatin exist not only between T. cruzi and higher eukaryotes but also among various forms of the parasite. The functional significance of these differences are currently under investigation. J. Cell. Biochem. 84: 832–839, 2002. © 2002 Wiley‐Liss, Inc.
Mutation in collagen gene induces cardiomyopathy in transgenic mice*
Authors: Miller Amanda D. , Tyagi Suresh C.
Published: August 2002

In many remodeling tissues, such as the heart, collagen degradation to provide new integrin‐binding sites is required for survival. However, complete loss of integrin signaling due to disconnection from extracellular matrix (ECM) leads to apoptosis and dilatation. To test the hypothesis that a mutation in type I collagen gene induces cardiomyopathy, we employed a metalloproteinase‐resistant collagen mutant homozygous transgenic male (B6,129‐Colla‐1) and compared with age‐sex matched wildtype C57BL/J6 control mice. At the age of 38–42 weeks, aortic and left ventricle (LV) pressure were measured. The LV wall thickness and diameter were measured by a digital micrometer. The levels of matrix metalloproteinase‐2 (MMP‐2) activity and cardiospecific tissue inhibitor of metalloproteinase‐4 (TIMP‐4) were measured by zymography and Western blot analyses, respectively. The levels of collagenolysis were measured by Western blot using anti‐collagen antibody. In transgenic and wildtype mice, end‐diastolic pressure (EDP) was 8.3 ± 1.7 and 6.5 ± 1.1 mmHg; LV diameter was 3.43 ± 0.07 and 2.94 ± 0.05 mm; wall thickness was 1.18 ± 0.03 and 1.28 ± 0.04 mm; end‐diastolic wall stress was 600 ± 158 and 347 ± 49 dynes/cm2, respectively. The increase in LV wall stress was associated with increased MMP‐2 activity, increased collagenolysis, and decreased levels of TIMP‐4. This leads to reduced elastic compliance in collagen mutant transgenic mice. The occurrence of cardiomyopathy in adult Colla‐1 mice may be a significant confounding factor as it may be indicative of increased basal levels of ECM disruption. This phenotype is what would be expected if collagen degradation normally supplies integrin ligands during cardiac muscle remodeling. J. Cell. Biochem. 85: 259–267, 2002. © 2002 Wiley‐Liss, Inc.
Reversible hypercondensation and decondensation of mitotic chromosomes studied using combined chemical–micromechanical techniques
Authors: Poirier Michael G. , Monhait Tamar , Marko John F.
Published: August 2002

We show that the chromatin in mitotic chromosomes can be drastically overcompacted or unfolded by temporary shifts in ion concentrations. By locally ‘microspraying’ reactants from micron‐size pipettes, while simultaneously monitoring the size of and tension in single chromosomes, we are able to quantitatively study the dynamics of these reactions. The tension in a chromosome is monitored through observation and calibration of bending of the glass pipettes used to manipulate the chromosomes. For concentrations > 500 mM of NaCl and > 200 mM of MgCl2, we find that the initially applied tensions of ∼ 500 pN relax to zero and that mitotic chromatin temporarily disperses in agreement with previous work (Maniotis et al. [1997] J. Cell. Biochem. 65:114–130). This unfolding occurs in about 1 s, and is reversible once the charge density is returned to physiological levels, if the exposure is not longer than ∼ 1 min. Low concentrations of NaCl (< 30 mM) also induces a decrease in tension and increase in size. We observe this swelling to be isotropic in experiments on chromosomes under zero tension, a behavior inconsistent with the existence of a well‐defined central chromosome ‘scaffold’. By contrast 10 mM of divalent cations (MgCl2 and CaCl2) induces an extremely rapid and reversible increase in tension and a reduction in the size of mitotic chromosomes. Hexaminecobalt trichloride (trivalent cation) has the same effect as MgCl2 and CaCl2, except the magnitude of force increase and size change are much larger. Hexaminecobalt trichloride reduces mitotic chromosomes to 65% of their original volume, indicating that at least 1/3 of their apparent volume is aqueous solution. These results indicate that chromatin inside mitotic chromatids has a large amount of conformational freedom allowing dynamic unfolding and refolding and that charge interactions play a central role in maintaining mitotic chromosome structure. J. Cell. Biochem. 85: 422–434, 2002. © 2002 Wiley‐Liss, Inc.
Stimulatory effect of endothelin‐1 on Na‐dependent phosphate transport and its signaling mechanism in osteoblast‐like cells
Authors: Masukawa Hiroko , Miura Yoshitaka , Sato Ikuko , Oiso Yutaka , Suzuki Atsushi
Published: August 2002

Endothelin‐1 (ET‐1) has been reported to modulate bone metabolism both in vivo and in vitro. In the present study, we investigated the effect of ET‐1 on inorganic phosphate (Pi) transport in osteoblast‐like cells, which is now considered to be important for the initiation of bone matrix calcification. ET‐1 time‐ and dose‐dependently stimulated Na‐dependent Pi transport in mouse calvaria‐derived osteoblast‐like MC3T3‐E1 cells, and this effect was dependent on transcriptional and translational process. Kinetic analysis indicated that the change in Pi transport activity induced by ET‐1 was due to alteration in the number of the Pi transporter. BQ123, a selective antagonist for ETA receptor, suppressed the ET‐1‐induced Pi transport, but BQ788, a selective antagonist for ETB receptor, had no effect. The inhibition of phosphoinositide hydrolysis by phospholipase C (PLC) partially attenuated the Pi transport by ET‐1. Propranolol, which inhibits phosphatidic acid phosphohydrolase, also suppressed ET‐1‐induced Pi transport. On the contrary, indomethacin did not affect the stimulatory effect of Pi transport by ET‐1. Calphostin C, a protein kinase C (PKC) inhibitor, significantly blunted the stimulatory effect of ET‐1 on Pi transport. Combined effect of PMA and ET‐1 on Pi transport was not additive. Pi transport induced by ET‐1 was also suppressed in PKC down‐regulated cells. In conclusion, the results of the present study indicate that in MC3T3‐E1 osteoblast‐like cells, ET‐1 acting through ET receptor links to a stimulation of Pi transport via activation of PKC through both phosphoinositide and phosphatidylcholine hydrolyses. © 2001 Wiley‐Liss, Inc.
SB203580 promote EGF‐stimulated early morphological differentiation in PC12 cell through activating ERK pathway†
Authors: New Liguo , Li Yingqiu , Ge Baoxue , Zhong Hongyin , Mansbridge Jonathan , Liu Kang , Han Jiahuai
Published: August 2002

MAP kinases have important role in PC12 cell differentiation, since the activities of both extracellular regulated protein kinase (ERK) and p38 have been indicated as necessary signal for PC12 cell differentiation. Epidermal growth factor (EGF) and NGF both activate ERK and p38 in PC12 cells, but only NGF trigger differentiation. It has been proposed that the duration of ERK activation determines the switch from proliferation to differentiation, since EGF causes more transient activation of ERK than NGF in PC12 cells. Here we report that treatment of PC12 cells with EGF in the presence of SB203580, a widely used p38 inhibitor, caused differentiation. The pro‐differentiation effect of SB203580 in EGF‐treated PC12 cells was found to be independent of its function of p38 inhibition but was through an effect on the ERK pathway that has been recently reported (Kalmes et al. [1999] FEBS Lett. 444: 71–74; Hall‐Jackson et al. [1999] Onc. 18: 2047–2054). We found that SB203580 by itself did not affect the activity of ERK1/2 but significantly extended EGF‐induced ERK activation in PC12 cells, which resulted in early morphological differentiation. Our data indicated that although both ERK and p38 are required for PC12 cell differentiation, activation of p38 is not required when ERK is superactivated. Our data provided further evidence for the threshold theory that differentiation is determined by the duration of ERK activation. J. Cell. Biochem. 83: 585–596, 2001. © 2001 Wiley‐Liss, Inc.