bluuebunny/crossref_metadata_2025 huggingface dataset:
HIV‐1 infection of primary effusion lymphoma cell line triggers Kaposi's sarcoma‐associated herpesvirus (KSHV) reactivation
Authors: Merat Rastine , Amara Ali , Lebbe Celeste , de The Hugues , Morel Patrice , Saib Ali
Published: August 2002

Kaposi's sarcoma‐associated herpesvirus (KSHV) is a gammaherpesvirus etiologically linked to primary effusion lymphoma (PEL), to a subset of multicentric Castleman's disease and to Kaposi's sarcoma (KS), the most common neoplasm associated with AIDS. Among KSHV‐infected individuals, the risk of KS is much higher in those with human immunodeficiency‐1 (HIV‐1) infection than among those with other types of immunosuppression, suggesting a direct action of HIV‐1 on KSHV replication. We show in our report that BC‐3 cells, a chronically KSHV‐infected B‐cell line of a PEL origin, are permissive to HIV‐1, offering a new tool for studying the interactions between these 2 viruses. In these cells, HIV‐1 infection leads to reactivation of latent KSHV genomes, as demonstrated by the expression of KSHV lytic viral mRNAs. Although recombinant HIV‐1 gp120 fails to enhance herpesvirus expression, transient transfection of the HIV‐1 trans‐activator Tat suffices to reactivate latent KSHV. By showing that HIV‐1 infection directly reactivates latent KSHV, our results suggest a direct role of HIV‐1 in the onset of KS in coinfected individuals. © 2001 Wiley‐Liss, Inc.
Regulation of CD1d expression by murine tumor cells: Escape from immunosurveillance or alternate target molecules?
Authors: Fiedler Tim , Walter Wolfgang , Reichert Torsten E. , Maeurer Markus J.
Published: August 2002

αβ+ TCR T cells recognize peptide fragments displayed by MHC‐class I or ‐class II molecules. Recently, additional mechanisms of antigen recognition by T cells have been identified, including CD1‐mediated presentation of nonpeptide antigens. Only a limited number of CD1 antigens is retained in the mouse, i.e., the group II CD1 antigens, which are split into CD1D1 and CD1d2. Several T cell subsets have been shown to interact with murine CD1 antigens, including NK cells or “natural T cells” with the invariant Vα14 Jα281 TCR chain. Even if TAP defects may prevent classical endogenous antigen presentation in tumor cell lines, antigen presentation via CD1 is still functional. Therefore, CD1‐mediated recognition of transformed cells by NK cells or “natural T cells” may represent an alternative way for immune surveillance. CD1 cell surface expression in murine tumor cell lines of different histology, including the B cell lymphoma A20, macrophage cell lines J774 and P388D1, mastocytoma P815, thymoma EL‐4, melanoma B16, colon adenocarcinoma MC‐38 and renal carcinoma Renca is regulated by Th1‐ (IFN‐γ), Th2‐ (IL‐4, IL‐10 and vIL‐10) or GM‐CSF (Th1/Th2) cytokines, depending on the tumor histology. In order to distinguish between CD1D1 and CD1d2 molecules, we examined differential expression of these CD1 isoforms by ratio RT‐PCR: A20, EL‐4, P815 and MC‐38 cells exclusively express CD1D1 transcripts but not CD1D2 mRNA independent of cytokine treatment. Decreased CD1d expression leads to reduced immune recognition of CD1d+ tumor cells by freshly isolated NK1.1+ effector cells as defined by cytolysis and IFN‐γ release. Thus, modulation of CD1 expression on tumor cells by cytokines may be advantageous to drive cellular anti‐tumor antigen directed immune responses directed against TAP‐independent, non‐classical MHC restricting molecules. © 2002 Wiley‐Liss, Inc.
Efficient tumor targeting by single‐domain antibody fragments of camels
Authors: Cortez‐Retamozo Virna , Lauwereys Marc , Hassanzadeh Gh. Gholamreza , Gobert Martine , Conrath Katja , Muyldermans Serge , De Baetselier Patrick , Revets Hilde
Published: August 2002

The variable domain of functional heavy chain antibodies (VHH) devoid of light chains, found in camels, constitute the smallest intact antigen‐binding domain fragment. Two camel single‐domain fragments, cAb‐Lys2 and cAb‐Lys3, recognizing an overlapping epitope of lysozyme with a dissociation constant of 2 nM and 65 nM, respectively, and a bivalent cAb‐Lys3 were investigated for their ability to target transgenic tumors expressing lysozyme on their membrane. Biodistribution studies revealed that these non‐immunogenic monomeric and bivalent camel single‐domain antigen binders specifically target lysozyme‐expressing tumors and metastatic lesions. The excess of antibody is rapidly eliminated from the blood circulation and no cAb retention was observed in normal organs. The tumor to organ cAb‐ratios at 2 and 8 hr were in the (2.1–10.8):1 and (6.2–23.7):1 range, respectively. The degree and specificity of tumor retention is independent of the affinity of the recombinant camel single‐domain fragments for their antigen and from their univalent monomeric (15 kDa) or bivalent format (33 kDa). This study demonstrates the successful and specific in vivo targeting of tumors by camel single‐domain fragments. It may open perspectives for their future use as tumor‐targeting vehicle, due to their small size, soluble behaviour and because they are non‐immunogenic and interact with epitopes that are less antigenic for conventional antibodies. © 2002 Wiley‐Liss, Inc.
Histologic classification of thymic epithelial tumors: Comparison of established classification schemes
Authors: Rieker Ralf J. , Hoegel Josef , Morresi‐Hauf Alicia , Hofmann Walter J. , Blaeker Hendrik , Penzel Roland , Otto Herwart F.
Published: August 2002

The object of our multicenter retrospective study was to compare the new histologic World Health Organization (WHO) classification and the classical histologic Bernatz classification in terms of interobserver agreement and prognostic importance. The influence of coexisting diseases was also analyzed using the Charlson score. We evaluated 218 patients from 5 different hospitals who were treated between 1967 and 1998. The statistical methods of analysis included Kaplan‐Meier estimates of survival curves and the application of Cox proportional hazards models to identify sets of prognostic factors for survival. Interobserver agreement was assessed by kappa coefficients. For both WHO and Bernatz classifications, interobserver agreement was good (weighted kappa > 0.87). However, the subdiversification of the “bioactive” WHO subgroup (B1, B2, B3) resulted in an interobserver agreement of only 0.49 within this group. In multivariable models, both the WHO classification and the Bernatz classification including carcinomas showed similar prognostic capabilities. The B3 type in the WHO classification and the predominantly epithelial type in the Bernatz classification had an intermediate prognostic ranking in comparison with the carcinomas and with the other subgroups. For both classifications, further simplification and subclassification into 3 subgroups led to classes with good discriminative power in respect to survival. In addition, very good interobserver agreement was observed in the simplified classifications. Comorbidity, sex, age of the patient and lymphofollicular hyperplasia had no major influence on overall survival. Both classifications showed similar prognostic power. Interobserver agreement of the type B subgroups was only moderate. By simplification of the classifications, subgroups with distinct survival could be identified. © 2002 Wiley‐Liss, Inc.
C‐myc gene expression alone is sufficient to confer resistance to antiestrogen in human breast cancer cells
Authors: Venditti Marcello , Iwasiow Barbara , Orr F. William , Shiu Robert P.C.
Published: August 2002

C‐myc is implicated in the initiation, progression and estrogen response of breast cancer. To further investigate the role of c‐myc in breast cancer, we have developed clonal MCF‐7 human breast cancer cell lines harboring a stably‐transfected human c‐myc gene, whose expression was stringently controlled by the bacterial reverse tetracycline transcription activator protein. The expression of the endogenous genomic c‐myc gene in MCF‐7 cells was abolished by the potent pure estrogen antagonist, ICI 182,780. Functional c‐Myc protein was identified by both Western immunoblotting and by its ability to transactivate a chimeric plasmid consisting of E‐box sequences upstream of the luciferase reporter gene. One MCF‐7 clone, 35im, was chosen for further characterization. C‐myc induction by doxycycline was rapid and dose dependent; c‐myc mRNA appeared as early as 30 min after doxycycline addition and stimulation of c‐myc expression required as little as 50 ng/ml doxycycline, with c‐myc mRNA levels reaching a plateau at 2.5 μg/ml doxycycline. ICI 182,780 or doxycycline (a tetracycline analog) treatment did not alter the mRNA levels of Max, the c‐myc binding partner. As in wildtype MCF‐7 cells, the growth of clone 35im was inhibited by 1 μM or less of ICI 182,780 and stimulated by 10 nM to 1 μM 17β‐estradiol. When maintained in a complete medium containing 5% normal fetal bovine serum (FBS) and ICI 182,780, doxycycline induced cell growth by 400% in an 8‐day assay. A similar level of growth was achieved with doxycycline treatment in cells that were arrested by the use of charcoal‐stripped FBS. Doxycycline had no effect on the growth of a control MCF‐7 clone (18c). Apoptosis, assessed by caspase‐dependent cleavage of poly(ADP‐ribose) polymerase, was unchanged in clone 35im cells after treatments with doxycycline or ICI 182,780. The present study demonstrates that c‐myc alone is sufficient to confer antiestrogen resistance in human breast cancer. Our novel c‐myc‐inducible MCF‐7 cell model offers a unique opportunity to study the diverse actions of the c‐myc proto‐oncogene in human breast cancer. © 2002 Wiley‐Liss, Inc.
Inhibition of prostate carcinoma establishment and metastatic growth in mice by an antiangiogenin monoclonal antibody
Authors: Olson Karen A. , Byers H. Randolph , Key Marc E. , Fett James W.
Published: August 2002

A neutralizing monoclonal antibody (MAb) 26‐2F to human angiogenin, a potent inducer of neovascularization, has been shown previously to prevent or delay the appearance of angiogenin‐secreting human colon, fibrosarcoma and lung tumor cell xenografts implanted subcutaneously (s.c.) into athymic mice. In an analogous model system, we report here that the antibody also prevents the establishment of PC‐3 androgen‐independent human prostate cancer tumors in, on average, 40% of treated mice (p < 0.0001, survivor analysis). Intriguingly, combining MAb 26‐2F together with cisplatin and suramin, 2 therapeutic agents that together showed little antitumor activity in the aforementioned model, resulted in an even greater degree of protection (71% protected, p = 0.009 compared to antibody treatment alone). This protective effect persisted several weeks after cessation of treatment. Additionally, prophylactic systemic administration of MAb 26‐2F dramatically reduced by 50% the formation of spontaneous regional metastasis originating from primary growth in the prostate gland of PC‐3M cells, highly metastatic variants of PC‐3. Protection from metastasis was still significant when treatment with MAb 26‐2F was delayed until after the primary tumor was well established. The antibody is not directly cytotoxic to either cell type, both of which secrete angiogenin in vitro and when growing as tumors in vivo, but changes the pattern of vascularity in primary tumors growing orthotopically. These findings, together with the observation that angiogenin protein and mRNA are apparently overexpressed in cancerous vs. normal human prostate tissues, demonstrate that angiogenin antagonism represents a promising new approach for preventing progression and metastasis of clinical prostate cancer. © 2002 Wiley‐Liss, Inc.
Healing of experimental colonic anastomoses: Effects of combined preoperative high‐dose radiotherapy and intraperitoneal 5‐fluorouracil
Authors: El‐Malt Mohamed , Ceelen Wim , van den Broecke Caroline , Cuvelier Claude , Van Belle Simon , De Neve Wilfried , de Hemptinne Bernard , Pattyn Piet
Published: August 2002

To study the effects of preoperative radiochemotherapy (RCT) on the healing of colonic anastomosis, the rectosigmoid colon in male Wistar rats was irradiated up to an end dose of 41.6 Gy (RT) or sham‐irradiated (SR). During the last 5 days of the irradiation schedule, 5‐fluorouracil (5‐FU) was administered intraperitoneally in either a high dose (20 mg/kg, chemotherapy‐high dose [CH]) or a low dose (10 mg/kg, chemotherapy‐low dose [CL]). Animals were randomly arranged into six groups: group I, control (SR + saline intraperitoneally); group II, RT only; group III, SR + CL; group IV, RT + CL; group V, SR + CH; group VI, RT + CH. Four days after RCT, a side‐to‐side anastomosis was constructed between the irradiated rectosigmoid and the nonirradiated caecum. Animals were killed 10 days postoperatively. No significant differences were found in the anastomotic bursting pressure or the bursting wall tension. In group VI, mitoses were less (P < 0.01) and mucosal ulceration was more (P = 0.03) pronounced compared to group I. Sclerotic arteries were seen in all irradiated groups and in animals that received high‐dose 5‐FU alone. 5‐FU administration in high or low dose, with or without RT, induced more inflammation in the submucosa compared to controls (P < 0.05). Conclusively, RCT has no detrimental effect on the mechanical strength of colonic anastomosis in this rat model. However, RCT with high‐dose 5‐FU induces more histological alterations at the anastomotic site. © 2001 Wiley‐Liss, Inc.
Adenosine acts through an A3 receptor to prevent the induction of murine anti‐CD3‐activated killer T cells
Authors: Hoskin David W. , Butler Jared J. , Drapeau Dennis , Haeryfar S.M. Mansour , Blay Jonathan
Published: August 2002

Adenosine, a purine nucleoside found at high levels in solid tumors, is able to suppress the recognition/adhesion and effector phases of killer lymphocyte‐mediated tumor cell destruction. Here, we demonstrate that adenosine, at concentrations that are typically present in the extracellular fluid of solid tumors, exerts a profound inhibitory effect on the induction of mouse cytotoxic T cells, without substantially affecting T‐cell viability. T‐cell proliferation in response to mitogenic anti‐CD3 antibody was impaired in the presence of 10 μM adenosine (plus coformycin to inhibit endogenous adenosine deaminase). Antigen‐specific T‐cell proliferation was similarly inhibited by adenosine. Anti‐CD3‐activated killer T (AK‐T) cells induced in the presence of adenosine exhibited reduced major histocompatibility complex‐unrestricted cytotoxicity against P815 mastocytoma cells in JAM and 51Cr‐release assays. Diminished tumoricidal activity correlated with reduced expression of mRNAs coding for granzyme B, perforin, Fas ligand and tumor necrosis factor (TNF)‐related apoptosis‐inducing ligand (TRAIL), as well as with diminished Nα‐CBZ‐L‐lysine thiobenzylester (BLT) esterase activity. Interleukin‐2 and interferon‐γ synthesis by AK‐T cells was also inhibited by adenosine. AK‐T cells express mRNA coding for A2A, A2B and A3 receptors, but little or no mRNA coding for A1 receptors. The inhibitory effect of adenosine on AK‐T cell proliferation was blocked by an A3 receptor antagonist (MRS1191) but not by an A2 receptor antagonist (3,7‐dimethyl‐1‐propargylxanthine [DMPX]). The A3 receptor agonists (N6‐2‐(4‐aminophenyl)ethyladenosine [APNEA] and N6‐benzyl‐5′‐N‐ethylcarboxamidoadenosine [N6‐benzyl‐NECA]) also inhibited AK‐T cell proliferation. Adenosine, therefore, acts through an A3 receptor to prevent AK‐T cell induction. Tumor‐associated adenosine may act through the same mechanism to impair the development of tumor‐reactive T cells in cancer patients. © 2002 Wiley‐Liss, Inc.
Tumor‐infiltrating endothelial cells and endothelial precursor cells in inflammatory breast cancer
Authors: Shirakawa Kazuo , Shibuya Masabumi , Heike Yuji , Takashima Shigemitsu , Watanabe Ichiro , Konishi Fumio , Kasumi Fujio , Goldman Corey K. , Thomas Kenneth A. , Bett Andrew , Terada Masaaki , Wakasugi Hiro
Published: August 2002

Inflammatory breast cancer (IBC) is a specific type of breast tumor that generally has a poor prognosis, in spite of recent advances in treatment. In the present study, semiquantitative reverse transcriptase polymerase chain reaction examination of resected specimens showed that angiogenic factors, not lymphangiogenic factors, are overexpressed in IBC tumors, compared with non‐IBC tumors. Immunohistochemical analysis of the specimens revealed a significantly higher population of tumor‐infiltrating (TI) endothelial cells (ECs) or endothelial precursor cells (EPCs) in tumor‐associated stroma of IBC specimens than in non‐IBC specimens. In a previous study, we examined the phenotype of host cells in response to transplanted IBC cells, using an established human IBC xenograft model (WIBC‐9) (Shirakawa et al., Cancer Res 2001;61:445–51). The data obtained in that study are consistent with the findings of the present study. To explore the therapeutic potential of blocking vascular endothelial growth factor (VEGF) and angiopoietin (Ang) pathways in IBC, established vectors encoding soluble Flt‐1 (sFlt‐1) and soluble Tie2 (sTie2) were injected directly into WIBC‐9. Both vectors produced growth inhibition ratios of WIBC‐9 that were significantly higher than those of a non‐IBC xenograft (MC‐5). Also, both vectors suppressed WIBC‐9 lung metastases. The efficacy correlated with the number of TI ECs/EPCs, which was determined by fluorescence‐activated cell sorting. These ECs/EPCs incorporated acetylated lipoprotein and were integrated within a HUVEC monolayer in vitro culture on day 5. © 2002 Wiley‐Liss, Inc.
NS‐398, a selective cyclooxygenase 2 inhibitor, inhibited cell growth and induced cell cycle arrest in human hepatocellular carcinoma cell lines
Authors: Cheng Jidong , Imanishi Hiroyasu , Amuro Yoshiki , Hada Toshikazu
Published: August 2002

Cyclooxygenase 2 (COX‐2) has been suggested to be associated with liver carcinogenesis. Several reports have shown that NSAIDs inhibit the growth of hepatocellular carcinoma cell lines. There is little evidence of how COX‐2 inhibitors regulate the proliferation of hepatocellular carcinoma cells or the mechanism involved. In our study, we investigated the growth‐inhibitory mechanism of a selective COX‐2 inhibitor, NS‐398, in 4 hepatocellular carcinoma cell lines by studying cell growth, COX‐2 and proliferating cell nuclear antigen (PCNA) expression, cell cycle distribution and the evidence of apoptosis. NS‐398 inhibited the growth of all 4 cell lines in a time‐ and dose‐dependent manner and the inhibitory effects were independent of the level of COX‐2 protein expression. PCNA expression was downregulated by NS‐398 in a dose‐independent manner. NS‐398 caused cell cycle arrest in the S phase with a reduction in cell numbers and cell accumulation in the G0/G1 phase, for all 4 cell lines. No evidence of apoptosis was observed in our present study. Our findings suggest that a selective COX‐2 inhibitor might serve as an effective tool for the chemoprevention and treatment of hepatocellular carcinomas. A reduction in cell number in the S phase may be an important event in cell cycle arrest caused by NS‐398 in hepatocellular carcinoma cell lines. © 2002 Wiley‐Liss, Inc.
Predictive value of histologic tumor necrosis after radiation
Authors: Chen Yuhchyau , Taghian Alphonse G. , Rosenberg Andrew E. , O'Connell John , Okunieff Paul , Suit Herman D.
Published: August 2002

Postsurgical evaluation of histologic changes of tumors after preoperative chemotherapy and/or radiotherapy has been a routine clinical practice of pathologists and oncologists. There appears to be secure evidence that the extent of tumor necrosis vs. viable tumor cells postchemotherapy is a clinically useful predictor of outcome. The significance of histologic tumor necrosis after radiotherapy, however, has not been clearly established and deserves further investigation. We investigated the correlation between histological extent of tumor necrosis, survival of tumor transplants, and radiation doses in an experimental model using three human tumor xenografts. Three human tumor cell lines were investigated: STS‐26, SCC‐21, and HGL‐21. Tumors were grown subcutaneously in athymic nude mice and received external beam radiation of different doses. Tumors were excised 2 weeks postirradiation. One‐half of the tumor was divided into 1‐mm3 fragments and transplanted to naive mice. The other half was examined for histologic tumor necrosis. Transplant survival was strongly correlated with radiation dose, TCDp (radiation dose that results in local tumor control in proportion, p, to irradiated tumors). In contrast, there was no clear association between transplant survival rate and the extent of tumor necrosis. The experimental model demonstrated a strong inverse correlation between radiation doses and tumor transplant survival. Histologic tumor necrosis did not correlate well with radiation doses or transplant survival rates. Despite common practices in histologic examination of tumors posttherapy, clinical interpretations and implications of histologic tumor necrosis after radiotherapy should be considered with caution. © 2001 Wiley‐Liss, Inc.
Involvement of αvβ 3 integrin and disruption of endothelial fibronectin network during the adhesion of the human ovarian adenocarcinoma cell line IGROV1 on the human umbilical vein cell extracellular matrix
Authors: Carreiras Franck , Thiébot Bénédicte , Leroy‐Dudal Johanne , Maubant Sylvie , Breton Marie‐france , Darbeida Halima
Published: August 2002

Like the majority of tumor cells, ovarian cancer cell growth is critically dependent on their neovascularization. Adhesion molecules and cellular events that lead to ovarian tumor cell interactions with endothelial extracellular matrix surrounding the vasculature are poorly identified. To understand the role of αvβ3 integrin and its ligand fibronectin in this process, we used in vitro coculture models with IGROV1 human ovarian adenocarcinoma cell line and human umbilical vein endothelial cells (HUVEC). Adhesion assays revealed a strong ability of IGROV1 cells to adhere to HUVEC‐ECM. αvβ3 is mainly implicated and seems to cooperate with α5β1 integrin in this event. Immunofluorescence staining revealed the presence of αvβ3 and α5β1 in IGROV1 cells adhering on HUVEC‐ECM at regions of cell sub‐stratum contacts. Furthermore, our data showed the absence of fibronectin staining in IGROV1 cells and the disruption of the HUVEC‐ECM fibrillar fibronectin network under IGROV1 cell influence. In situ experiments in ovarian neoplastic tissue corroborated the absence of fibronectin in the tumor and its strong detection in vasculature. These findings suggest the active participation of αvβ3 and α5β1 integrins and the reorganization of endothelial fibronectin during the adhesion of IGROV1 cells to HUVEC‐ECM whereas IGROV1 cells seem to be unable to synthesize fibronectin. Thus, fibronectin integrin receptors expressed by ovarian tumor cells and endothelial fibronectin may be of importance in ovarian carcinoma neovascularization and during tumor‐vasculature interactions. © 2002 Wiley‐Liss, Inc.
Family transitions in Latin America: first intercourse, first union and first birth
Authors: Heaton Tim B. , Forste Renata , Otterstrom Samuel M.
Published: August 2002

This paper examines the initiation of sexual activity, first marriage and first birth as key steps in family formation. These events mark the transition to adulthood and generally occur in the late teens and early twenties in most Latin American countries. Using data from Demographic and Health Surveys, we examine the timing of these events across birth cohorts, comparing urban and rural areas, countries, cultural regions and educational groups. The average life course for young women in Latin America consists of the initiation of intercourse as adolescents, entering partnerships about one year later, and giving birth about a year after that. This pattern remained fairly stable over the time period examined. Education substantially delays these family transitions and the education effect is similar in most countries. Latin American women with secondary levels of schooling are significantly less likely to experience early marriage or parenthood relative to those with no schooling. Urban residence also delays entry into sexual activity, marriage and parenthood at the bivariate level. However, once education is controlled for, the effect of residence reverses – that is, urban residence is associated with early transition ages. A combination of national boundaries and cultural groupings explain more of the variation in transition rates than either grouping alone. Thus, we conclude that both national and cultural factors appear to influence family transitions in Latin America, in addition to the effects of education and urbanisation. Copyright © 2002 John Wiley & Sons, Ltd.
A new fast block matching algorithm based on complexity‐distortion optimization
Authors: Tai Pol Lin , Liu Chii Tung , Wang Jia Shung
Published: August 2002

Most fast block matching algorithms ignore the efficiency in motion compensation within each checking step. In order to achieve better‐compensated performance, the limited computational complexity should be allocated more carefully into each block. It means that the fast block matching algorithm can be viewed as a kind of rate‐distortion optimization problem. The complexity‐distortion optimal fast block matching algorithm should find the maximized quality of the compensated image under a target computational complexity. In order to approach the optimal complexity‐distortion solution, some strategies are developed. For example, a domination‐based motion vector prediction technique is developed to set the initial motion vector for each block. A predictive complexity‐distortion benefit list is established to predict the compensated benefit for each block. Also, a three‐level pattern searching is employed to check the candidate motion vector. Experimental results show that our proposed algorithm outperforms significantly the three‐step search. For example, in “Salesman,” the average checkpoints for one block is 33 by using the three‐step search. The average checkpoint is 1.75 by using our proposal algorithm under the same average PSNR condition. © 2002 Wiley Periodicals, Inc. Int J Imaging Syst Technol 12, 63–67, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ima.10012
Low‐income adolescent mothers' knowledge about domains of child development
Authors: Tamis‐Lemonda Catherine S. , Shannon Jacqueline , Spellmann Mark
Published: August 2002

Sixty low‐income adolescent mothers of children ranging in age from birth to 28 months were asked to estimate the ages at which children are first able to engage in specific activities in cognitive, language, motor, play, and social development. In general, mothers were quite knowledgeable about the ordering of developmental abilities relative to one another, but were less knowledgeable about the developmental timing of abilities. With respect to timing, mothers tended to underestimate the onset of all developmental abilities. That is, mothers predicted that children's developmental abilities would appear earlier than they actually do. Mothers' knowledge about cognitive, language, and motor abilities was stronger than their knowledge about abilities in play and social development. Across domains, mothers were more accurate at estimating the ages of abilities that emerge in the first year than those occurring during children's second and third years. Findings are discussed with respect to societal emphases on different domains of development, and the potential implications of unrealistic expectations for adolescent parenting. ©2002 Michigan Association for Infant Mental Health.
Postneonatal mental and motor development of infants exposed in utero to opioid drugs
Authors: Hans Sydney L. , Jeremy Rita J.
Published: August 2002

We compared the mental and motor development of 33 infants from innercity, African American families whose mothers used opioid drugs during pregnancy with that of 45 infants from demographically comparable families where the mothers were not users of opioids. We found that during the first 2 years of life, the children exposed to opioid drugs showed poorer functioning on Bayley Scales mental and psychomotor development indices as well as on Infant Behavior Record ratings of mental and motor functioning. Although both groups of children performed in the normal range during infancy, both groups showed sharp declines in their developmental scores during the second year of life relative to norms. The poorer performance of the opioid‐exposed group in mental development was related to social‐environmental risk factors; in psychomotor development, to reduced birth weight. © 2001 Michigan Association for Infant Mental Health.
Protective action of the serine protease inhibitor N‐tosyl‐L‐lysine chloromethyl ketone (TLCK) against acute soman poisoning
Authors: Cowan F. M. , Broomfield C. A. , Lenz D. E. , Shih T.‐M.
Published: August 2002

Soman‐poisoned rats display cholinergic crisis, a systemic mast cell degranulation characteristic of anaphylactic reactions and an excitotoxin‐like sequential seizure and neuronal degeneration. The protection of guinea pigs from soman lethality by prophylactic administration of the serine protease inhibitor suramin suggests a possible proteolytic component in soman poisoning. The present study tested the effect of N‐tosyl‐L‐lysine chloromethyl ketone (TLCK), an inhibitor of trypsin‐like serine proteases, on soman‐induced toxic signs (convulsions, righting reflex) and survival time. Nine control guinea pigs receiving 2 × LD50 (56 µg kg−1, s.c.) of soman immediately followed by a therapeutic dose of atropine sulfate (17.4 mg kg−1 i.m.) experienced severe convulsions, and 8/9 lost the righting reflex. Six of these nine animals expired within 65 min; the three remaining animals survived 24 h to termination of the experiment. When a second group of animals were given TLCK (12 mg kg−1, i.p.) 30 min prior to a 2 × LD50 soman challenge and atropine‐sulfate therapy, 5/9 experienced convulsions and only 3/9 lost the righting reflex. All nine animals survived beyond 4 h, with six surviving to 24 h. Compared with soman controls, prophylaxis with TLCK significantly prevented the loss of righting reflex (P = 0.05) and enhanced 4‐h survival (P = 0.005). Although, convulsions were reduced and 24‐h survival was improved in TLCK‐treated animals, these results were not statistically significant. The protection from soman toxicity by chemically distinct protease inhibitors such as suramin and TLCK suggests a role for pathological proteolytic pathways in soman intoxication. Copyright © 2001 John Wiley & Sons, Ltd.
On carbide dissolution in an as‐cast ASTM F‐75 alloy
Authors: Caudillo M. , Herrera–Trejo M. , Castro M. R. , Ramírez E. , González C. R. , Juárez J. I.
Published: August 2002

The solution treatment of an as‐cast ASTM F‐75 alloy was investigated. Microstructural evolution was followed during thermal processing, in particular with regard to the content and type of carbides formed. To evidence any probable carbide transformations occurring during the heating stage, as well as to clarify their effect on the carbide dissolution kinetics, three heating rates were studied. Image analysis and scanning electron microscopy techniques were used for microstructural characterization. For the identification of precipitates, these were electrolytically extracted from the matrix and then analyzed by X‐ray diffraction. It was found that the precipitates in the as‐cast alloy were constituted by both a M23C6 carbide and a σ intermetallic phase. The M23C6 carbide was the only phase identified in solution‐treated specimens, regardless of the heating rate employed, which indicated that this carbide dissolved directly into the matrix without being transformed first into an M6C carbide, as reported in the literature. It was found that the kinetics of dissolution for the M23C6 carbide decreased progressively during the solution treatment, and that it was sensitive to the heating rate, decreasing whenever the latter was decreased. Because the M23C6 carbide was not observed to suffer a phase transformation prior to its dissolution into the matrix, the effect of the heating rate was associated to the morphological change occurred as the specimens were heated. The occurrence of the observed phases was analyzed with the aid of phase diagrams computed for the system Co–Cr–Mo–C. © 2001 Wiley Periodicals, Inc. J Biomed Mater Res 59: 378–385, 2002
Hydroxyapatite deposition by electrophoresis on titanium sheets with different surface finishing
Authors: Ágata de Sena Lídia , Calixto de Andrade Mônica , Malta Rossi Alexandre , de Almeida Soares Gloria
Published: August 2002

Hydroxyapatite coatings are commonly applied to metallic biomedical implants to accelerate osseointegration. These coatings, usually produced by plasma spray techniques, can be obtained by alternative processes, like biomimetic process, electrolytic deposition, or electrophoretic process as well. Electrophoretic deposition of hydroxyapatite exhibits several advantages like simplicity and low cost. In this article, titanium sheets with three different surface finishing were coated with hydroxyapatite by using electrophoresis. Surface treatments include: (1) abrading with SiC paper; (2) abrading with SiC paper plus electrolytic etch with H3PO4 solution; and (3) blasting with alumina powder followed by etch with a solution containing H2O2 and HF. Stoichiometric hydroxyapatite was used to coat titanium sheets. Blasted samples were also coated using a calcium‐deficient hydroxyapatite. SEM, XRD, and FTIR were employed to characterize titanium substrates and coatings produced. Results show that electrophoretic process can produce a uniform thin layer, satisfactorily adhered, of hydroxyapatite on treated titanium samples. Furthermore, sintering at 800 °C do not promote the decomposition of calcium‐deficient hydroxyapatite. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 60: 1–7, 2002
Solution deposition of hydroxyapatite on titanium pretreated with a sodium ion implantation
Authors: Pham M. T. , Matz W. , Grambole D. , Herrmann F. , Reuther H. , Richter E. , Steiner G.
Published: August 2002

Titanium surfaces were treated by exposing them to a beam of sodium ions. Sodium titanate was shown to be incorporated within the oxidic titanium surface. The ion‐implanted surfaces were examined for their reactivity by immersion in a simulated body fluid, which showed the formation of surface‐bound hydroxyapatite. The surface was characterized by X‐ray diffraction, Fourier transform infrared spectroscopy, X‐ray photoelectron spectroscopy, and optical and electron microscopy. The surface hydroxyl concentration was determined using the nuclear reaction 1H(15N, αγ)12C. Surface‐related parameters that may affect hydroxyapatite nucleation are discussed in terms of the electrical double layer. © 2001 Wiley Periodicals, Inc. J Biomed Mater Res 59: 716–724, 2002
Fluorinated surface‐modifying macromolecules: Modulating adhesive protein and platelet interactions on a polyether‐urethane
Authors: Jahangir A. R. , McClung W. G. , Cornelius R. M. , McCloskey C. B. , Brash J. L. , Santerre J. P.
Published: August 2002

Polyether‐urethanes (PEUs) have been the materials of choice for the manufacture of conventional blood‐contacting devices. Nevertheless, biostability and blood compatibility are still among the principal limitations in their long‐term application. Studies investigating the development of protective coatings for PEUs have shown that degradation can be reduced with the use of fluorinated surface‐modifying macromolecules (SMMs). It has also been hypothesized that SMM‐modified PEU surfaces may exhibit improved blood compatibility because other studies have shown a modulation in fibrinogen adsorption onto these surfaces. To determine the blood compatibility of a PEU‐containing fluorinated SMMs, a series of in vitro experiments were designed to study the pattern of protein adsorption from plasma and then to assess the nature of platelet adhesion and activation on each substrate. Western blot analysis as well as single protein studies revealed that the dominant “adhesive proteins” [fibrinogen (Fg), fibronectin (Fnc), and vitronectin (Vnc)] were adsorbed on two of the SMM‐containing PEUs in lower amounts relative to unmodified base. Platelet adhesion and activation data further highlighted the differences among the various substrates. It was shown that the unmodified base had a higher number of adhered platelets relative to the SMM‐modified surfaces, and that of the SMM‐containing substrates, which showed the lowest levels of adhesive proteins also, exhibited significantly lower platelet densities. Close morphological examination further revealed that platelets residing on these latter substrates were not appreciably activated. Based on the current evidence, it is believed that the fluorinated SMMs demonstrate good potential for the development of surfaces with minimal thrombogenic character in in vivo applications. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 60: 135–147, 2002
Collagen and bone viscoelasticity: A dynamic mechanical analysis
Authors: Yamashita Junro , Li Xiaoe , Furman Benjamin R. , Rawls H. Ralph , Wang Xiaodu , Agrawal C. Mauli
Published: August 2002

The purpose of this study was to explore the effects of changes in Type I collagen on the viscoelasticity of bone. Bone coupons were heated at either 100 or 200 °C to induce the thermal denaturation of Type I collagen. Half of these specimens were rehydrated after heat treatment; the other half were tested in a dry condition. The degree of denatured collagen (DC%) was analyzed by a selective digestion technique with the use of α‐chymotrypsin. Isothermal (37 °C) and variable temperature tests (scans from 35 to 200 °C) were performed with the use of a dynamic mechanical analyzer to evaluate changes in bone viscoelastic properties as a function of collagen damage, specifically, changes in the loss factor (tan δ) and storage modulus (E′) were assessed. Significant collagen denaturation occurred only when bone was heated at 200 °C irrespective of the hydration condition. Also, DC% did not show a significant effect on tan δ. However, higher values of tan δ were observed in wet samples compared to dry specimens. The temperature‐scan tests revealed that the hydration condition, but not DC%, significantly affected the behavior of tan δ. However, E′ was not strongly influenced either by DC% or by water content. These results suggest that at a constant frequency the denaturation of collagen triple‐helical molecules may have few effects on the viscoelasticity of bone, but moisture may play a prominent role in determining this property. © 2001 Wiley Periodicals, Inc. J Biomed Mater Res (Appl Biomater) 63: 31–36, 2002
Electrospun nanofibrous structure: A novel scaffold for tissue engineering
Authors: Li Wan‐Ju , Laurencin Cato T. , Caterson Edward J. , Tuan Rocky S. , Ko Frank K.
Published: August 2002

The architecture of an engineered tissue substitute plays an important role in modulating tissue growth. A novel poly(D,L‐lactide‐co‐glycolide) (PLGA) structure with a unique architecture produced by an electrospinning process has been developed for tissue‐engineering applications. Electrospinning is a process whereby ultra‐fine fibers are formed in a high‐voltage electrostatic field. The electrospun structure, composed of PLGA fibers ranging from 500 to 800 nm in diameter, features a morphologic similarity to the extracellular matrix (ECM) of natural tissue, which is characterized by a wide range of pore diameter distribution, high porosity, and effective mechanical properties. Such a structure meets the essential design criteria of an ideal engineered scaffold. The favorable cell–matrix interaction within the cellular construct supports the active biocompatibility of the structure. The electrospun nanofibrous structure is capable of supporting cell attachment and proliferation. Cells seeded on this structure tend to maintain phenotypic shape and guided growth according to nanofiber orientation. This novel biodegradable scaffold has potential applications for tissue engineering based upon its unique architecture, which acts to support and guide cell growth. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 60: 613–621, 2002
The influence of material and design features on the mechanical properties of transpedicular spinal fixation implants
Authors: Hahn Michael , Nassutt Roman , Delling Günter , Mahrenholtz Oskar , Schneider Erich , Morlock Michael
Published: August 2002

This study describes the finding and performance of mechanical strength and corrosion testing procedures for comparative examination of multiple internal transpedicular spine fixators. Seven different implant models from five different manufacturers were compared regarding their bending strength and fatigue resistance. Because of the unacceptably high levels of time and material that they require, ISO and ASTM testing standards are not applicable to comparative testing. In addition, there is a lack of knowledge about clinically defined and proven strength‐limit values. Therefore, actual standard testing procedures have been modified and extended to corrosion testing. Overall, the effort necessary to obtain reproducible comparative data has been reduced significantly. Although a reduced number of implants of each type were available for destructive testing, the results revealed fundamental differences in the tested implants between different materials and design features. During fatigue testing some of the implants showed poor corrosion properties. Because spinal fixation implants tend to be used as long‐duration implants, corrosion testing as well as comparative strength testing with clinically successful implant models should be performed as preclinical evaluations. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res (Appl Biomater) 63: 354–362, 2002
Adhesion/decalcification mechanisms of acid interactions with human hard tissues
Authors: Yoshioka M. , Yoshida Y. , Inoue S. , Lambrechts P. , Vanherle G. , Nomura Y. , Okazaki M. , Shintani H. , Van Meerbeek B.
Published: August 2002

In order to study adhesion/decalcification mechanisms of acid interactions with human hard tissues such as bones and teeth, the chemical interaction of five carboxylic acids (acetic, citric, lactic, maleic, and oxalic) and two inorganic acids (hydrochloric and nitric) with enamel and two synthetic hydroxyapatite (HAp) powders with, respectively, a high and a low crystallinity were analyzed using X‐ray photoelectron spectroscopy (XPS), atomic absorption spectrophotometry (AAS), and spectrophotometry (S). X‐ray diffraction revealed that the crystallinity of the highly crystallized HAp was considerably higher than that of enamel while the crystallinity of the poorly crystallized HAp was similar to that of dentin and bone. XPS of acid‐treated enamel demonstrated for all carboxylic acids ionic bonding to calcium of HAp. AAS and S showed for both HAps that all carboxylic and inorganic acids except oxalic acid extracted Ca significantly more than P, leading to a Ca/P ratio close to that of synthetic HAp (2.16 w/w). Oxalic acid extracted hardly any Ca, but substantially more P, leading to a significantly smaller Ca/P ratio than that of HAp. AAS showed that the calcium salt of oxalic acid hardly could be dissolved, whereas the calcium salts of all the other acids were very soluble in their respective acid solution. These results confirm the adhesion/decalcification concept (AD‐concept) previously advanced. Depending on the dissolution rate of the respective calcium salts, acids either adhere to or decalcify apatitic substrates. It is concluded that the AD‐concept that originally dictated the interaction of carboxylic acids with human hard tissues can be extended to inorganic acids, such as hydrochloric and nitric acid. Furthermore, HAp crystallinity was found not to affect the adhesion/decalcification behavior of acids when interacting with apatitic substrates, so that the AD‐concept can be applied to all human hard tissues with varying HAp crystallinity. © 2001 Wiley Periodicals, Inc. J Biomed Mater Res 59: 56–62, 2002
Protein adsorption and human osteoblast‐like cell attachment and growth on alkylthiol on gold self‐assembled monolayers
Authors: Scotchford Colin A. , Gilmore Christopher P. , Cooper Elaine , Leggett Graham J. , Downes Sandra
Published: August 2002

Protein adsorption and growth of primary human osteoblasts on self‐assembled monolayers of alkylthiols on gold (SAMs) with carboxylic acid and hydroxyl and methyl termini were investigated. Single‐component SAMs and SAMs patterned by photolithographic techniques were used. Cell growth on patterned SAMs demonstrated preferences for one pattern region in all combinations of alkylthiols, with the hierarchical preference COOH > OH > CH3. Patterned SAMs and immunochemistry were used to investigate adsorption of fibronectin and albumin with respect to different alkylthiol termini. Fibronectin adsorption from both pure solution and serum containing cell culture medium (SDMEM) followed the sequence COOH > OH > CH3. Albumin adsorption from pure solution followed the sequence OH > COOH > CH3; from SDMEM the sequence was CH3 > OH > COOH. Cell attachment to SAMs with the above termini, after preadsorption with fibronectin, albumin, or mixtures of fibronectin and albumin, was measured. Attachment was maximal on COOH‐terminated SAMs precoated with fibronectin. Attachment to COOH was significantly reduced only when fibronectin was omitted from the protein preadsorption solution. On OH and CH3 SAMs increasing the proportion of albumin in the solution was sufficient to significantly reduce cell attachment. The distribution vinculin and the integrins α5β1 and αvβ3 indicated that focal contact formation by cells varied with alkylthiol termini in the following sequence: COOH > OH > CH3. © 2001 Wiley Periodicals, Inc. J Biomed Mater Res 59: 84–99, 2002
Effect of mechanical perturbation on the release of PGE2 by macrophages in vitro
Authors: Grottkau B. E. , Noordin S. , Shortkroff S. , Schaffer J. L. , Thornhill T. S. , Spector M.
Published: August 2002

Macrophages play numerous roles in both physiologic and pathologic processes. Along with fibroblasts, they comprise the synovial tissue that forms the lining of musculoskeletal joint capsules and bursae, and they often envelop implants. During the process of phagocytosing prosthesis‐related particles, macrophages in peri‐implant tissue release inflammatory mediators. Little is known, however, about the response of these cells to mechanical perturbation, which often is a component of the physical environment of the cell. Mouse peritoneal macrophages were grown on a flexible membrane in vitro and a dynamic 1‐Hz spatially uniform sinusoidal strain pattern imparted to the elastomeric substrate. The effect of mechanical strain on prostaglandin (PG) E2 release was evaluated using cells that were activated by lipopolysaccharide (LPS) as well as by those that were not. The results are compared with the levels of PGE2 stimulated by metallic particles. Strain magnitudes of 4 and 8% applied for 1 h resulted in almost a twofold increase in the release of PGE2 from LPS‐stimulated cells (p < 0.05) and nonstimulated macrophages (p < 0.07), compared with nonperturbated controls. No release was elicited by a challenge of metal particles. These findings demonstrate for the first time an effect of mechanical force on the release of an inflammatory mediator by macrophages. This response may help to explain the macrophage‐mediated processes underlying the osteolysis associated with loose prostheses in bone and suggests a mechanism for the inflammation of synovial tissues by excessive mechanical strain. © 2001 Wiley Periodicals, Inc. J Biomed Mater Res 59: 288–293, 2002