bluuebunny/crossref_metadata_2025 huggingface dataset:
Ischemia‐induced neuronal expression of the microglia attracting chemokine secondary lymphoid‐tissue chemokine (SLC)
Authors: Biber Knut , Sauter André , Brouwer Nieske , Copray Sjef C.V.M. , Boddeke Hendrikus W.G.M.
Published: August 2002

Recently, it has been demonstrated that secondary lymphoid‐tissue chemokine (SLC) is constitutively expressed in secondary lymphoid organs and controls the homing of naive T‐cells and mature dendritic cells. By screening cDNA isolated from ischemic mouse brain, we found expression of SLC mRNA 6 h up to 4 days after the onset of ischemia. In situ hybridization combined with immunohistochemistry showed neurons expressing SLC mRNA in the ischemic area of the cortex. SLC mRNA expression was also found in cultured neurones after various treatments known to induce neuronal death, but not in cultured glial cells. Stimulation with SLC induced intracellular calcium transients and chemotaxis in cultured microglia. Since mRNA encoding CXCR3, an alternative receptor for SLC, but no CCR7 mRNA was found in microglia, we suggest that the effects of SLC on microglia are mediated by CXCR3. This assumption was corroborated by cross‐desensitization experiments using IP‐10 as a ligand for CXCR3. The inducible expression of SLC in neurones acting on microglia suggests a new and important role of SLC in the neuroimmune system. We propose that SLC is part of a neurone‐microglia signaling system which is related to pathological conditions of the brain like ischemia. GLIA 34:121–133, 2001. © 2001 Wiley‐Liss, Inc.
Microglial cells protect cerebellar granule neurons from apoptosis: Evidence for reciprocal signaling
Authors: Polazzi Elisabetta , Gianni Tatiana , Contestabile Antonio
Published: August 2002

The microglia are the immune cell population of the nervous system and play important roles both in normal function and in disease. Reciprocal neuron–microglia interactions are not well understood, in particular those concerning the crosstalk between the two cell populations when neuronal damage does occur. We have used a well‐established model of apoptosis in cerebellar granule neurons to test the effect of co‐culturing microglial cells with them or of exposing them to microglia‐conditioned medium. Microglial cells, derived from cortical or cerebellar mixed glial cultures and plated over cerebellar granule neurons, protected these neurons from apoptosis induced by shifting them, at 7 days in vitro, for 24 h from a depolarizing (high‐potassium) to a nondepolarizing (low‐potassium) medium. The same result was achieved when microglial cells obtained from mixed glial cortical cultures were plated over a membrane well insert in the culture chamber, permitting medium exchange without physical contact with granule neurons. A similar result was obtained when the low‐potassium, apoptosis‐inducing medium was conditioned by 48‐h exposure to microglial cells; 24‐h exposure to microglial cells was not enough to confer neuroprotective capability to the conditioned medium. However in double‐conditioned medium experiments, in which the medium was first exposed to apoptotic neurons and then to microglial cells, unknown signal(s) released by apoptotic neurons, conferred to the 24‐h conditioned medium a strong neuroprotective action, similar to that observed in the co‐cultures experiments. This finding, together with the results from co‐culture experiments, is explained by admitting that molecules released in the medium by apoptotic neurons potentiate the anti‐apoptotic activity of microglia. Our results, therefore, demonstrate not only that normally microglial cells release in the medium molecule(s) able to rescue neurons from apoptotic death, but that unknown diffusible signal(s) from apoptotic neurons enhance(s) microglial neuroprotective properties as well. GLIA 36:271–280, 2001. © 2001 Wiley‐Liss, Inc.
Molecular characterization of cell substratum attachments in human glial tumors relates to prognostic features
Authors: Belot Nathalie , Rorive Sandrine , Doyen Isabelle , Lefranc Florence , Bruyneel Erik , Dedecker Robert , Micik Sibel , Brotchi Jacques , Decaestecker Christine , Salmon Isabelle , Kiss Robert , Camby Isabelle
Published: August 2002

Glioma cell attachments to substratum play crucial roles in the invasion by glioma cells of normal brain tissue. These attachments are mediated through interactions between extracellular matrix (ECM) components, integrins, focal adhesion‐linked molecules, and the actin cytoskeleton. In the present study, we investigate the molecular elements involved in cell substratum attachments in human glial tumors and their potential relationships to prognostic features. We used 10 human glioma cell lines, for which we characterized glial differentiation by means of quantitative RT‐PCR for nestin, vimentin, and GFAP mRNA. We quantitatively determined the amounts of laminin, fibronectin, vitronectin, and thrombospondin secreted by these glioma cell lines in vitro, as well as the amount of each of the eight β integrin subunits and the adhesion complex‐related molecules, including talin, vinculin, profilin, zyxin, α‐actinin, paxillin, and VASP. After quantification of the levels of migration and invasion of these 10 cell lines in vitro and, through grafts into the brains of nude mice, of their biological aggressiveness in vivo, it appeared that the levels of the β5 integrin subunit and α‐actinin were directly related to biological aggressiveness. These experimental data were clinically confirmed because increasing immunohistochemical amounts of the β5 integrin subunit and α‐actinin were directly related to dismal prognoses in the case of astrocytic tumors. In addition, we show that the β4 integrin subunit are expressed significantly more in oligodendrogliomas than in astrocytic tumors. A potential role for the β8 integrin subunit in glioma cell substratum attachments is also emphasized. GLIA 36:375–390, 2001. © 2001 Wiley‐Liss, Inc.
Naproxen in heterocyclic chemistry: Novel syntheses of triazoles, triazolothiadiazines, triazolothiadiazoles, and triazolothiadiazepine bearing an asymmetric carbon atom and radiostability of the biologically active compounds
Authors: Ammar Y. A. , Ghorab M. M. , El‐Sharief A. M. Sh. , Mohamed Sh. I.
Published: August 2002

Several s‐triazoles 2, 7a, 10, 12; s‐triazolo[3,4‐b][1,3,4]thiadiazines (3–5); s‐triazolo[3,4‐b][1,3,4]thiadiazoles (6, 8, 11, 15); and s‐triazolo[3,4‐b][1,3,4]thiadiazepine (14) were synthesized starting from 2‐(6‐methoxy‐2‐naphthyl)propanoic acid (1) (Naproxen). The structures of the synthesized compounds were elucidated by elemental analyses and spectral data. Compounds 2, 5, 11, 12, 14, and 15 exhibited a remarkable antifungal activity compared with the standard fungicide Mycostatine. Radiosterilization of the biologically active compounds 2, 5, 11, and 14 in the dry state may prove to be applicable (retaining their structures unchanged up to 40 kGy). © 2002 Wiley Periodicals, Inc. Heteroatom Chem 13:199–206, 2002; Published online in Wiley Interscience (www.interscience.wiley.com). DOI 10.1002/hc.10019
One pot syntheses of thiazol‐2‐hydrazone, pyridino[2,3‐d]pyridazine, pyrazolo[3,4‐d]pyridazine, and isoxazolo[4,5‐d]pyridazine derivatives
Authors: Mohareb Rafat M. , Fleita Daisy H.
Published: August 2002

Reactions of the pyridazine derivatives 1a–c with phenyl isothiocyanate followed by heterocyclization with ethyl chloroacetate gave the thiazolidinone derivatives 6a–c. The reactivity of 6a towards some chemical reagents was studied. © 2002 Wiley Periodicals, Inc. Heteroatom Chem 13:258–262, 2002; Published online in Wiley Interscience (www.interscience.wiley.com). DOI 10.1002/hc.10026
A facile synthesis of pyrrolo[3,2‐d]pyrimidines from 6‐azidouracils and ylide phosphoranes
Authors: Abdou Wafaa M. , Fahmy Amin F. M. , Kamel Azza A.
Published: August 2002

A series of the title compounds, 9‐deazaxanthines, was regioselectively prepared in reasonable yields as major products from the reactions of 6‐azidouracils 1a,b with stabilized ester‐2a,b or keto‐2c ylide phosphoranes and a moderated phosphorus ylide 3, instead of the expected triazoles. Side products were also observed wherein pyrimido[5,4‐g]pteridine‐2,4,5,7‐tetrone (15) and other fused ring systems or acyclic‐substituted uracil derivatives were isolated. A comparative study on the reactivity of 1a in analogy to 1b toward phosphoranes is also described. © 2002 Wiley Periodicals, Inc. Heteroatom Chem 13:357–365, 2002; Published online in Wiley Interscience (www.interscience.wiley.com). DOI 10.1002/hc.10048
Metastatic squamous cell carcinoma of the neck from an unknown primary: Management options and patterns of relapse
Authors: Iganej Shahrokh , Kagan Robert , Anderson Paul , Rao Aroor , Tome Michael , Wang Ricardo , Dowlatshahi Morteza , Cosmatos Harry , Morgan Thomas
Published: August 2002

Purpose

Management of squamous cell carcinoma of undetermined primary tumors in the head and neck region is controversial. Here we report the Southern California Kaiser Permanente experience with these patients.

Methods and Materials

From January 1969 through December 1994, 106 patients were eligible for this retrospective analysis. Distribution of nodal staging was as follows: 14 N1, 27 N2A, 39 N2B, 2 N2C, and 24 N3. Initial treatment included excisional biopsy alone in 12, radical neck dissection alone in 29, radiotherapy alone in 24, excisional biopsy followed by radiotherapy in 15, and radical neck dissection plus postoperative radiation in 26 patients.

Results

Except for two patients, all patients have had a minimum follow‐up of 5 years. Overall, 57 patients (54%) have had recurrences. Only two patients (3%) who had received radiotherapy as part of their initial treatment had an appearance of a potential primary site inside the irradiated field vs 13 patients (32%) who had not received radiotherapy (p = .006). Combined modality therapy resulted in fewer neck relapses, particularly in patients with advanced neck disease. Including salvage, surgery alone as the initial treatment resulted in 81% ultimate tumor control above the clavicle for patients with N1 and N2a disease without extracapsular extension. The 5‐year survival for the entire population was 53%. Radiotherapy alone resulted in poor survival in patients with advanced/unresectable neck disease. No significant difference in survival based on the initial treatment was found. The statistically significant adverse factors in determining survival included advanced nodal stage and the presence of extracapsular extension.

Conclusions

Radiotherapy is very effective in reducing the rate of appearance of a potential primary site. However, in the absence of advanced neck disease (N1 and N2A without extracapsular extension), radiotherapy can be reserved for salvage. Radiotherapy alone results in poor outcomes in patients with advanced/unresectable neck disease, and incorporation of concurrent chemotherapy and cytoprotective agents should be investigated. © 2002 Wiley Periodicals, Inc. Head Neck 24: 236–246, 2002; DOI 10.1002/hed.10017
Competitive Hebbian learning and the hippocampal place cell system: Modeling the interaction of visual and path integration cues
Authors: Guazzelli Alex , Bota Mihail , Arbib Michael A.
Published: August 2002

The hippocampus has long been thought essential for implementing a cognitive map of the environment. However, almost 30 years since place cells were found in rodent hippocampal field CA1, it is still unclear how such an allocentric representation arises from an egocentrically perceived world. By means of a competitive Hebbian learning rule responsible for coding visual and path integration cues, our model is able to explain the diversity of place cell responses observed in a large set of electrophysiological experiments with a single fixed set of parameters. Experiments included changes observed in place fields due to exploration of a new environment, darkness, retrosplenial cortex inactivation, and removal, rotation, and permutation of landmarks. To code for visual cues for each landmark, we defined two perceptual schemas representing landmark bearing and distance information over a linear array of cells. The information conveyed by the perceptual schemas is further processed through a network of adaptive layers which ultimately modulate the resulting activity of our simulated place cells. In path integration terms, our system is able to dynamically remap a bump of activity coding for the displacement of the animal in relation to an environmental anchor. We hypothesize that path integration information is computed in the rodent posterior parietal cortex and conveyed to the hippocampus where, together with visual information, it modulates place cell activity. The resulting network yields a more direct treatment of partial remapping of place fields than other models. In so doing, it makes new predictions regarding the nature of the interaction between visual and path integration cues during new learning and when the system is challenged with environmental changes. Hippocampus 2001;11:216–239. © 2001 Wiley‐Liss, Inc.
A policy of introducing a new contract and funding system of general practice in Estonia
Authors: Lember Margus
Published: August 2002

The socialist bloc of post‐war Europe was obliged to follow the Soviet example with a hierarchical, centrally controlled health care system based on polyclinics and other facilities providing extensive specialist services at the first level of contact. All the countries of Central and Eastern Europe have now expressed their wish to totally change their health care systems. Changes in these countries include: the introduction of market economy mechanisms in health care, an increased focus on population health needs in guiding health care systems, and the possibility of introducing a more general type of care at primary level. Patient expectations of access, choice and convenience are factors in shaping new models of health care delivery. Appropriate timing is the key determinant of the success of reforms. In Estonia the beginning of the 1990s was the time when several interest groups in society supported changes in the health care system. The first step after regaining independence was the reintroduction of a Bismarck‐type insurance system. In the late 1990s the primary care reforms have changed the initial plans and elements of a National Health Service were introduced, especially general practitioners' lists, capitation payment and gate‐keeping principles. The family medicine reform in Estonia has two main objectives: introduction of general practice as a specialty into Estonian health care and changing the remuneration system of primary care doctors. The specific tasks are: to provide practising primary care doctors with opportunities for retraining to gain the specialty status of a general practitioner, to create a list system for the population to register with a primary care doctor, to introduce a partial gate‐keeping system and to give the status of the independent contractor to primary care doctors. Copyright © 2002 John Wiley & Sons, Ltd.
The acute effects of an extract of Bacopa monniera (Brahmi) on cognitive function in healthy normal subjects
Authors: Nathan P. J. , Clarke J. , Lloyd J. , Hutchison C. W. , Downey L. , Stough C.
Published: August 2002

The Ayurvedic medicine Bacopa monniera (Brahmi) has been shown to exert cognitive enhancing effects in animals. The current study examined the acute effects of an extract of Bacopa monniera on cognitive function in normal healthy human subjects. The study was a double‐blind, placebo‐controlled independent group design in which subjects were randomly allocated to one of two treatment conditions, Bacopa monniera (300 mg) (n = 18) or placebo (n = 20). Neuropsychological testing was conducted before and 2 h after drug administration. No significant changes were found on any of the tests. The findings suggest that Bacopa monniera, at least for the dose administered, has no acute effects on cognitive functioning in normal healthy subjects. Copyright © 2001 John Wiley & Sons, Ltd.
Hysteresis‐based flood‐wave analysis using the concept of strain
Authors: Mishra Surendra Kumar , Singh Vijay P.
Published: August 2002

Hysteresis represents a loop in a rating curve and is a phenomenon which closely resembles that occurring in stress–strain curves used for studying the elastic properties of solid substances in engineering mechanics. Earlier hysteresis‐based studies used for defining floodwave propagation in open channels have qualitatively shown that hysteresis is an index of energy loss during floodwave propagation. Using the concept of elasticity, this paper introduces a new term called flow strain (defined as the ratio of change in discharge to the initial discharge) for investigating hysteresis. The usefulness of this new term is evaluated with use of four dam‐break studies. The study reveals that:

flow strain is a function of three wave speeds, Seddon speed, Lagrange speed, and elastic speed;

a single linear reservoir concept frequently used in flood routing is a specific variant of the Seddon speed formula;

the non‐linear storage–discharge relationship, widely used in overland flow modelling, is a variant of the kinematic wave representation;

the discharge ordinates on the recession part of a hydrograph follow a simple first‐order autoregressive form;

the hysteresis, phase difference and logarithmic decrement all define attenuation and are indices of energy loss during floodwave propagation.

Copyright © 2001 John Wiley & Sons, Ltd.
Effects of the spatial organization of agricultural management on the hydrological behaviour of a farmed catchment during flood events
Authors: Moussa Roger , Voltz Marc , Andrieux Patrick
Published: August 2002

Field limits, tillage practices and ditch networks constitute man‐made hydrological discontinuities in farmed catchments, and are expected to influence hydrological response during flood events. The purpose of this study is to assess the role of human impact, especially the existence of tillage practices and ditch network, on flood events. The study area is the farmed catchment of Roujan (0·91 km2) located in Southern France for which a spatially distributed hydrological model, MHYDAS, was developed and tested. The model considers the catchment as a series of interconnected field parts linked to the ditch network. Descriptions are provided for the main model procedures: computation of Hortonian excess rainfall on fields using the Green and Ampt approach, conversion of excess rainfall to surface runoff, interaction between ditch network and groundwater using a simple Darcian model and flood routing through the ditch network using the diffusive wave model. To analyse the role of both tillage practices and the ditch network, two sets of sensitivity analysis of the model were applied. The first set studied the role of tillage practices by comparing the actual spatial distribution of tillage practices on the catchment with three hypothetical scenarios. The second set studied the role of the ditch network by comparing the actual man‐made ditch network with a hypothetical drainage network automatically extracted from a digital elevation model. Results show the importance of the role of tillage and the ditch network on the form of the hydrograph, the lag time, the runoff volume and the peak discharge. This technique could also be applied to study the impact of land use change on the hydrological behaviour of the catchment. Copyright © 2002 John Wiley & Sons, Ltd.
P53: An ubiquitous target of anticancer drugs
Authors: Blagosklonny Mikhail V.
Published: August 2002

The p53 tumor suppressor can induce growth arrest, apoptosis and cell senescence. Not surprisingly, p53 is an appealing target for therapeutic intervention. Although current anticancer agents do not directly interact with p53, these agents (including DNA damaging drugs, antimetabolites, microtubule‐active drugs and inhibitors of the proteasome) cause accumulation of wt p53. Depending on the p53 status of cancer cells, diverse therapeutic strategies are under development. These include pharmacological rescue of mutant p53 function and reactivation of wt p53 in E6‐expressing cells. For protection of normal cells, strategies range from abrogation of wt p53 induction, thereby decreasing the toxicity of DNA damaging agents, to activation of wt p53‐dependent checkpoints, thereby protecting cells against cell cycle‐dependent therapeutics. © 2001 Wiley‐Liss, Inc.
Antitumor activity of the selective epidermal growth factor receptor‐tyrosine kinase inhibitor (EGFR‐TKI) Iressa® (ZD1839) in an EGFR‐expressing multidrug‐resistant cell line in vitro and in vivo
Authors: Naruse Ichiro , Ohmori Tohru , Ao Yoko , Fukumoto Hisao , Kuroki Toshio , Mori Masatomo , Saijo Nagahiro , Nishio Kazuto
Published: August 2002

Selective tyrosine kinase inhibitors are regarded as promising antitumor agents for cancer treatment. Iressa® (ZD1839) is an orally active, selective EGFR‐TKI (epidermal growth factor receptor‐tyrosine kinase inhibitor) that blocks signal transduction pathways implicated in cancer cell proliferation, survival and other host‐dependent processes promoting cancer growth. The cellular mechanisms of ZD1839 action against human malignant cells and drug‐resistant cells were evaluated in vitro. Among the cell lines tested, ZD1839 showed a strong growth‐inhibitory effect in vitro on human leukemic cells resistant to phorbol ester. This cell line, K562/TPA, shows a non‐P‐glycoprotein‐mediated multidrug‐resistant phenotype. The IC50 value of ZD1839 on K562/TPA was approximately 400‐fold lower than that on the parental K562 cell (K562 = 12 ± 2 μM; K562/TPA = 0.025 ± 0.002 μM) in vitro as determined by a dye formation assay. The expression of EGFR and EGFR mRNA was clearly present in K562/TPA but not in parental K562 cells as determined by Western blotting and RT‐PCR. EGFR was autophosphorylated in K562/TPA detected by the antiphosphotyrosine antibody. The in vivo antitumor effects of ZD1839 on K562 and K562/TPA cells were also investigated in BALB/c nude mice. K562/TPA cells transplanted subcutaneously into mice disappeared completely with ZD1839 treatment (20 mg/kg/day, days 3–9). This was not the case in K562 cells. These results suggest that ZD1839 is highly active against tumor cells with non‐P‐glycoprotein‐mediated multidrug resistance that express EGFR. Iressa® is a trademark of AstraZeneca (Cheshire, UK). © 2001 Wiley‐Liss, Inc.
Prostate cancer mortality reduction by screening: Power and time frame with complete enrollment in the European randomised screening for prostate cancer (ERSPC) trial
Authors: de Koning Harry J. , Liem Michael K. , Baan Caroline A. , Boer Rob , Schröder Fritz H. , Alexander on behalf of ERSPC Freda E.
Published: August 2002

From 1992–2001, 7 countries in Europe gradually recruited men for the European Randomised Screening for Prostate Cancer (ERSPC) trial. Centres recruit different age groups and have different designs for recruiting and countries have different underlying risks for prostate cancer. Recruitment has reached 163,126 men aged 55–69 at entry now. Our purpose was to calculate the power of the trial and at what point in time can statistically significant differences in prostate cancer mortality be expected. Recruitment data were collected from the screening centres. We calculated the expected number of prostate cancer deaths in each follow‐up year, based on national statistics and expected rate in trial entrants. The power was calculated using different assumptions on intervention effect and contamination rate and also if the ERSPC trial would cooperate with other trials. With an assumed 25% intervention effect in men actually screened and a 20% contamination rate, the trial will reach a power of 0.86 in 2008. With an assumed intervention effect of 40%, the power reaches 0.90 in 2003–2004. Pooling data with those of the Prostate, Lung, Colorectal and Ovary (PLCO) trial early is expected to improve the power to 79% (20% intervention effect) to 92% (40% intervention effect PLCO). Adding more centres with compliance rates lower than 45% decreases the power of the trial. The ERSPC trial has sufficient power to detect a significant difference in prostate cancer mortality between the 2 arms if the true reduction in mortality by screening is 25% or more or if contamination remains limited to 10% if the true effect is 20% or more. If early detection and treatment turns out to have a stronger effect as may be suggested by observational data, the ERSPC trial is likely to conclusively show that within the next 5 years. © 2001 Wiley‐Liss, Inc.
Novel epidemiologic evidence for the association between fermented fish sauce and esophageal cancer in South China
Authors: Ke Li , Yu Ping , Zhang Z. Xin
Published: August 2002

Previous studies have suggested that fermented fish sauce is related to an increased risk for nasopharyngeal, thyroid and gastric cancers and has suspicious carcinogenic and promoting effects in the laboratory, but these reports have not investigated the association between this agent and esophageal cancer in population. Therefore, we investigated the relationship between esophageal cancer and consumption of fermented fish sauce, alcohol and tobacco after adjusting other risk factors using data from a large hospital‐based case‐control study in Chaoshan area of China. The subjects for analysis included 1,248 cases (median age 58.5 [range 29–82] years, 936 males, 312 females, some 50% with the habit of fermented fish sauce eating) with squamous cell carcinoma of the esophagus and the same amount of controls matched by sex and age. A significant increase in risk (OR 3.21; 95% CI 2.45–4.19) for eating fermented fish sauce compared to not eating and a significant dose‐response relationship was found with the consumption of fermented fish sauce (p for trend < 0.001). In comparison based on the binary variables, the OR for the subjects with fermented fish sauce eating and current smoking was 15.5 with a 95% CI of 8.14–29.3, relative to those exposed to neither habit. The joint effect of fermented fish sauce (F) and smoking (S) was more than additive (F * S > F + S: 15.5 > 1 + (5.6 − 1) + (6.6 − 1)), but the effect for fermented fish sauce and alcohol was not found. It is concluded that risks of esophageal cancer in the population were substantially associated with fermented fish sauce. Further epidemiologic and experimental study are required to find a biologic causal relationship between them. © 2002 Wiley‐Liss, Inc.
Effects of cytarabine and various anthracyclins on platelet activation: Characterization of in vitro effects and their possible clinical relevance in acute myelogenous leukemia
Authors: Foss Brynjar , Ulvestad Elling , Hervig Tor , Bruserud Øystein
Published: August 2002

Previous in vitro studies have demonstrated that normal platelets and platelet‐released mediators can alter in vitro characteristics of human acute myelogenous leukemia (AML) blasts. To further investigate whether platelets can be expected to adhere to and thereby affect AML blasts through their release of soluble mediators into a common microenvironment, we investigated (i) the effects on platelet activation by cytotoxic drugs commonly used in AML therapy; (ii) the occurrence of circulating activated platelets in acute leukemia patients; and (iii) the in vivo and in vitro adherence of platelets to AML blasts. The anthracyclins daunorubicin and idarubicin increased the expression of activation‐associated membrane molecules (GPIIb/IIIa, CD62P, CD63) by normal platelets, daunorubicin then having the strongest effect. In contrast, cytarabine, epirubicin, doxorubicin and mitoxantrone had no significant effects. Although AML patients did not show increased levels of activated platelets in the circulation, adhesion of platelets to AML blasts was demonstrated both in vivo and in vitro. These results suggest that platelets and AML blasts may locate to common in vivo microenvironments, and platelet‐derived soluble mediators may thereby affect the functional characteristics of the leukemia cells. © 2002 Wiley‐Liss, Inc.
Increased expression of T‐fimbrin gene after DNA damage in CHO cells and inactivation of T‐fimbrin by CpG methylation in human colorectal cancer cells
Authors: Sasaki Yasushi , Itoh Fumio , Kobayashi Toshihisa , Kikuchi Takefumi , Suzuki Hiromu , Toyota Minoru , Imai Kohzoh
Published: August 2002

When DNA damage is induced by unprogrammed extrinsic events, activating‐cell‐cycle checkpoints delay cell‐cycle progression in the G1 or G2 phases and allow repair of a damaged template. In this study, we evaluated changes in gene expression upon radiation‐induced G2 cell‐cycle arrest using Chinese hamster ovary (CHO) cells. T‐fimbrin, an actin‐binding protein, was overexpressed in CHO cells in which G2 arrest had been induced by X‐radiation. Northern blot analysis revealed that T‐fimbrin gene expression was induced not only by X‐radiation but also by a topoisomerase II inhibitor, etoposide. Transfection of CHO cells with a vector encoding T‐fimbrin antisense RNA demonstrated that reduced T‐fimbrin expression induced alterations in cell‐cycle control; radiation‐induced G2 arrest was short and decreased in cells transfected with antisense T‐fimbrin. Additionally, T‐fimbrin gene expression was suppressed in a human colorectal cancer cell line, SW948, because of promoter‐specific DNA methylation. These results suggest that downregulation of T‐fimbrin may be involved in cancer development through G2/M cell‐cycle control in mammalian cells. © 2002 Wiley‐Liss, Inc.
Living arrangements and support relationships among elderly Indonesians: case studies from Java and Sumatra
Authors: Beard Victoria A. , Kunharibowo Yacobus
Published: August 2002

Throughout Asia the proportions of national populations aged 65 years and above are predicted to grow rapidly over the next 50 years. While this process of ageing is already well underway in the more economically developed countries in East Asia, it is just beginning to accelerate in Southeast Asia. This increase in the proportion of the elderly population creates new demands for social and economic support, and simultaneously brings to the forefront the concern that changing household structures will translate into a decline in support for the elderly. Presently, in Indonesia most elderly parents co‐reside with their adult children. However, preliminary studies provide some evidence that casts doubt on the presumed relationship between co‐residence and receipt of support. This paper uses qualitative case studies of elderly parents and their adult children to examine the connection between living arrangements and support relationships. We collected data for the case studies through the use of in‐depth interviews, direct observation, and a structured household questionnaire. We conducted the case studies in urban and rural areas on Java and Sumatra, respectively, and we focused upon two distinct sociocultural groups: the Javanese and the Batak Karo. The use of different geographical locations allowed us to evaluate how the urban and rural environment, as well as traditional sociocultural norms, shaped the preferences and behaviours of elderly parents and their adult children. This paper argues for the conceptual separation of living arrangements and support relationships, and it suggests the existence of a support continuum that has six distinct levels, ranging from level 1 (elderly parents completely supporting adult child) to level 5 (adult child completely supporting elderly parents), with level 6 indicating no exchange of support whatsoever. Primarily, ‘support’ refers to transfers of time and money; however, the case‐study approach facilitates the evaluation of less quantifiable aspects of support, including companionship, knowledge and experience. Based on evidence from the case studies, it appears that some elderly parents completely support their adult children; however, in most cases the relationship between parent and child is reciprocal. Because these relationships are often subtle, they are easily missed when researchers rely on highly structured methods of data collection. This study of the support continuum in Indonesia will be of use to anyone seeking to understand the complex and nuanced relationships that exist between the elderly and their children. The case studies, besides providing a window through which to observe the Indonesian household, also provide insights that will be useful to those who wish to design structured survey instruments. Copyright © 2001 John Wiley & Sons, Ltd.
Estimation of unsaturated flow in layered soils with the finite control volume method
Authors: Arampatzis George , Tzimopoulos Christos , Sakellariou‐Makrantonaki Maria , Yannopoulos Stavros
Published: August 2002

Water movement in unsaturated soil is described by Richards' equation, which is strongly nonlinear and cannot be solved analytically. For this reason numerical methods such as finite difference and finite element methods have been used to solve it. This paper presents another numerical solution of Richards' equation, based on the finite control volume method. This method has important advantages over other numerical methods, such as conservativeness of the system and flexibility of the grid intervals. To validate the numerical model a series of experiments were carried out in the laboratory in a vertical column of unsaturated two‐layered soil (coarse and fine sand). The upper boundary condition was a second kind or Newman one and the lower boundary condition was a third kind or Newton's law condition. The soil water content was measured using the γ‐ray absorption method, while the water pressure in the pore media was measured using a tensiometer system with ceramic cups and pressure transducers. The numerical results of the new computational scheme are in good agreement with the experimental points. Copyright © 2001 John Wiley & Sons, Ltd.
Co‐extrusion of biocompatible polymers for scaffolds with co‐continuous morphology
Authors: Washburn Newell R. , Simon Carl G. , Tona Alessandro , Elgendy Hoda M. , Karim Alamgir , Amis Eric J.
Published: August 2002

A methodology for the preparation of porous scaffolds for tissue engineering using co‐extrusion is presented. Poly(ϵ‐caprolactone) is blended with poly(ethylene oxide) in a twin‐screw extruder to form a two‐phase material with micron‐sized domains. Selective dissolution of the poly(ethylene oxide) with water results in a porous material. A range of blend volume fractions results in co‐continuous networks of polymer and void spaces. Annealing studies demonstrate that the characteristic pore size may be increased to larger than 100 μm. The mechanical properties of the scaffolds are characterized by a compressive modulus on the order of 1 MPa at low strains but displaying a marked strain‐dependence. The results of osteoblast seeding suggest it is possible to use co‐extrusion to prepare polymer scaffolds without the introduction of toxic contaminants. Polymer co‐extrusion is amenable to both laboratory‐ and industrial‐scale production of scaffolds for tissue engineering and only requires rheological characterization of the blend components. This method leads to scaffolds that have continuous void space and controlled characteristic length scales without the use of potentially toxic organic solvents. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 60: 20–29, 2002
Effects of pH on human bone marrow stromal cells in vitro: Implications for tissue engineering of bone
Authors: Kohn David H. , Sarmadi Mojgan , Helman Joseph I. , Krebsbach Paul H.
Published: August 2002

The objective of this study was to address the hypothesis that changes in extracellular pH alter collagen gene expression, collagen synthesis, and alkaline phosphatase activity in bone marrow stromal cells (BMSCs). Potential effects of pH on cell function are of particular importance for tissue engineering because considerable effort is being placed on engineering biodegradable polymers that may generate a local acidic microenvironment on degradation. Human and murine single‐cell marrow suspensions were plated at a density of 2 × 104 cells/cm2. After 7 days in culture, the pH of the culture medium was adjusted to one of six ranges: ≥7.8, 7.5.–7.7, 7.2–7.4, 6.9–7.1, 6.6–6.8, or ≤6.5. After 48 h of exposure to an altered pH, alkaline phosphatase activity and collagen synthesis decreased significantly with decreasing pH. This decrease was two‐to threefold as pH decreased from 7.5 to 6.6. In contrast, α1(I) procollagen mRNA levels increased two‐ to threefold as pH was decreased. The trend in osteocalcin mRNA expression was opposite to that of collagen. Small shifts in extracellular pH led to significant changes in the ability of BMSCs to express markers of the osteoblast phenotype. These pH effects potentially relate to the microenvironment supplied by a tissue‐engineering scaffold and suggest that degrading polymer scaffolds may influence the biologic activity of the cells in the immediate environment. © 2002 John Wiley & Sons, Inc. J Biomed Mater Res 60: 292–299, 2002; DOI 10.1002/jbm.10050
Initial interaction of U2OS cells with noncoated and calcium phosphate coated titanium substrates
Authors: ter Brugge P. J. , Dieudonne S. , Jansen J. A.
Published: August 2002

From previous studies, we know that calcium phosphate (CaP) coated implants stimulate bone formation compared to uncoated implants. Nevertheless, the mechanism by which substrate surface characteristics affect cell function is unclear. In this study, we examined the initial interaction (30 min to 24 h) of U2OS cells with titanium substrates with or without a CaP coating. The effect of substrate roughness was also studied. When cell attachment was studied, we found that cells attached more readily to rough than to smooth surfaces. Also, more cells attached to the uncoated than to the CaP coated surface. After 24 h, cell numbers were similar for all substrate surfaces. Further, cells spread to a larger area on noncoated titanium than on the CaP coated substrates. At 24 h, the sequence of cell size was smooth titanium > rough titanium > CaP coated titanium. Shape measurements showed differences in cell shape between the cells on the different materials only at 7 h, not at different culture times. Cells expressed α2, α3, α5, α6, αv, and β1 subunits. Expression of α1, α4, αvβ3, β3, β4, and β7 was extremely low or was not found.

The β1 integrin expression was higher on the coated than on the noncoated titanium at 3 h, but not on the other studied times. Expression of α2, α5, α6, and αv expression was found to be upregulated at 24 h compared to earlier culture times on coated titanium, but not on uncoated titanium substrates. From this we conclude that the surface characteristics of a material (roughness and composition) can affect the initial interaction of cells with the material. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 61: 399–407, 2002
Slow‐releasing potential of vancomycin‐loaded porous hydroxyapatite blocks implanted into MRSA osteomyelitis
Authors: Saito Tomoyuki , Takeuchi Ryohei , Hirakawa Kazuo , Nagata Nobuhito , Yoshida Takuji , Koshino Tomihisa , Okuda Kenji , Takema Morio , Hori Toshihiko
Published: August 2002

Although antibiotic‐loaded hydroxyapatite blocks have been used for the treatment of chronic osteomyelitis, their long‐term potential for releasing antibiotic into human bones is not well known. Five patients with chronic osteomyelitis due to methicillin‐resistant Staphylococcus aureus (MRSA) infection were effectively treated with local implantation of vancomycin‐loaded hydroxyapatite blocks. Blocks were removed during the following reconstructive surgeries when the releasing capability of the blocks, and the bacteriocidal activity of the remaining vancomycin in these blocks could be evaluated. Vancomycin was rapidly released within 1 month after implantation, and by 3 months 90% of vancomycin had leaked from the blocks. At 18 months vancomycin still remained in a bacteriocidal form in the hydroxyapatite blocks, though the blocks had no releasing potential or the eluted vancomycin had been changed to a different form. Vancomycin‐loaded porous hydroxyapatite blocks would be useful for the treatment of chronic osteomyelitis or implant‐associated osteomyelitis due to MRSA.© 2002 Wiley Periodicals, Inc. J Biomed Mater Res (Appl Biomater) 63: 245–251, 2002
Early dissolution of a morsellised impacted silicate‐free bioactive glass in metaphyseal defects
Authors: Griffon D. J. , Dunlop D. G. , Howie C. R. , Gilchrist T. , Salter D. M. , Healy D. M.
Published: August 2002

The purpose of this study was to evaluate the biological properties of idealized, morsellised impacted Corglaes®, a soluble silicate‐free glass. Twenty‐two sheep underwent implantation of pellets in six metaphyseal defects in both rear limbs. Particle size distribution of all aggregates (except the autograft) approached the ideal logarithmic grading line and all implants were impacted to a standard compactive effort. Treatment groups consisted of (1) empty defect (negative control), (2) autograft (positive control), (3) allograft (clinical control), (4) allograft idealized with Corglaes®, (5) 50/50 allograft/Corglaes® and (6) Corglaes®. Defects were sealed with polymethylmethacrylate. Healing of the defects was evaluated at 7 weeks (n=6) and 14 weeks (n=16) with computed tomography, histology, and histomorphometry. Remnants of Corglaes® were found within one of the defects 7 weeks after implantation. Defects filled with mixtures containing 50% or 100% Corglaes® were less dense, contained less bone and more fibrous tissue than defects with allograft, autograft, or allograft idealized with Corglaes®. Allograft idealized with Corglaes®may be considered for impaction grafting in revision hip arthroplasty, as well as local delivery of antibiotics. However, further studies and potential revision of the agent are required before mixtures containing concentrations of Corglaes® equal to or higher than 50% can be recommended.
Biodegradable poly(ethylene oxide)/poly(ϵ‐caprolactone) multiblock copolymers
Authors: Cohn Daniel , Stern Theodor , González M. Fernanda , Epstein Julia
Published: August 2002

A series of poly(ethylene oxide) (PEO)/poly(ϵ‐caprolactone) (PCL) containing biodegradable poly(ether ester urethane)s, covering a wide range of compositions, were synthesized and characterized. The synthesis consisted of a two‐step process. During the first step, the ring‐opening reaction of ϵ‐caprolactone was carried out, initiated by the hydroxyl terminal groups of the PEO chain. The second step involved the chain extension of these PCL–PEO–PCL tri‐ mers with hexamethylene diisocyanate. By varying either the ethylene oxide/ϵ‐caprolactone ratio or the length of both segments, we obtained a series of polymers having different morphologies and displaying a broad range of properties. © 2001 Wiley Periodicals, Inc. J Biomed Mater Res 59: 273–281, 2002
Prospective, randomized, sequential, crossover trial of large‐volume vs. normal‐volume leukapheresis procedures: Effects on subpopulations of CD34+ cells
Authors: A. Humpe , J. Riggert , S. Koch , T.J. Legler , U. Munzel , M. Köhler
Published: August 2002

Some data exist on the influence of leukapheresis volume on the number of harvested peripheral blood hematopoietic progenitor cells (HPC), but less is known about the influence on the composition of HPC. We therefore performed a prospective, randomized crossover trial to evaluate the effect of large‐volume (LVL) vs. normal‐volume leukapheresis (NVL) on subpopulations of CD34+ cells in the harvest product of 15 patients with breast cancer and 8 patients with non‐Hodgkin's lymphoma. Patients were randomly assigned to start either with an LVL on day 1 followed by an NVL on day 2 or vice versa. The number of HPC, the extraction efficiency defined as difference between yield in the harvest and decrease in peripheral blood, and the relative proportion as well as the absolute numbers of CD34+ cells coexpressing CD38, CD90, HLA‐DR, CD117, CD7, CD19, CD41, or CD33 were evaluated. There was no significant difference with regard to the percentages of the subsets on comparison of LVL to NVL procedures. Only the absolute median number of CD34+HLA‐DR− cells was significantly (P=0.02) higher in LVL harvests compared with the corresponding NVL components, which can be explained on the basis of the higher yield and the higher extraction efficiency in LVL compared with NVL. LVL results in a higher yield of CD34+ cells and leads to an intra‐apheresis recruitment of HPC but the relative composition of the harvested CD34+ cells is not changed significantly. In addition, the amount of early, HLA‐DR−, hematopoietic HPC seems to be increased by an LVL. J. Clin. Apheresis. 16:109–113, 2001. © 2001 Wiley‐Liss, Inc.
Arsenite stabilizes IκBα and prevents NF‐κB activation in IL‐1 β‐stimulated Caco‐2 cells independent of the heat shock response*
Authors: Hershko Dan D. , Robb Bruce W. , Hungness Eric S. , Luo Guangju , Hasselgren Per‐Olof
Published: August 2002

Recent studies suggest that sodium arsenite downregulates NF‐κB activity by inhibiting phosphorylation and subsequent degradation of IκBα. Many effects of sodium arsenite are secondary to induction of heat shock proteins. The role of the heat shock response in arsenite‐induced inhibition of NF‐κB, however, is not known. We examined the involvement of the heat shock response in arsenite‐induced inhibition of NF‐κB activity in IL‐1β‐stimulated Caco‐2 cells, a human colorectal adenocarcinoma cell line with enterocytic properties. Treatment of the cells with IL‐1β resulted in increased IκB kinase activity, reduced levels of IκBα and increased NF‐κB DNA binding activity. Sodium arsenite blocked all of these responses to IL‐1β without inducing changes in heat shock factor activity or heat shock protein levels. Results from additional experiments showed that the protective effect of sodium arsenite on IκBα was not influenced by the oxygen radical scavenger catalase or by inhibitors of the MAP‐kinase signaling pathway. The present results suggest that sodium arsenite stabilizes IκBα and prevents NF‐κB activation in IL‐1β‐stimulated Caco‐2 cells independent of the heat shock response. In addition, stabilization of IκBα by sodium arsenite does not require oxygen radical formation or activation of the MAP kinase signaling pathway. J. Cell. Biochem. 84: 687–698, 2002. © 2002 Wiley‐Liss, Inc.
Oxidative stress signalling in the apoptosis of Jurkat T‐lymphocytes
Authors: Chiaramonte Raffaella , Bartolini Enrico , Riso Patrizia , Calzavara Elisabetta , Erba Daniela , Testolin Giulio , Comi Paola , Sherbet Gajanan V.
Published: August 2002

The pathways of transduction of oxidative stress signals have been studied using the Jurkat T cell model. The oxidative stress was induced by exposure of the cells to 100 μM H2O2. DNA damage was detected within 15 min after commencement of treatment. DNA damage repair occurred within about 1 h in cells exposed to oxidative stress for 15 min. In continuous exposure to stress, DNA repair was slower and control levels of DNA integrity were not reached. DNA repair did not involve gene transcription. H2O2 at 100 μM caused cell death by necrosis as well as by apoptosis. Both these processes were induced by 15 min exposure to the stress stimulus. However, some important differences were found between necrosis and apoptosis. Necrosis was more rapid, began within an hour of treatment and continued to increase during the full duration of the experiment. But apoptosis was seen after 4 h from treatment and was conspicuous between 6 and 20 h after the start of treatment. The necrotic phase preceded apoptosis, although these did show an overlap. In the necrotic phase, Bcl‐2, Caspase 8 genes were down regulated. The 6–20 h phase characterised by a marked increase in apoptosis is accompanied by the up regulation of both Bcl‐2 and Caspase genes. Expression of the Fas and p53 genes was not altered in either phase. We also analysed the levels of expression of the scavenging genes whose gene products are involved in detoxification. No modulation of the antioxidant enzymes, catalase, Cu/Zn superoxide dismutase and glutatione peroxidase was detectable. J. Cell. Biochem. 82:437–444, 2001. © 2001 Wiley‐Liss, Inc.