bluuebunny/crossref_metadata_2025_split huggingface dataset:
Covariates and confounding in epidemiologic studies using metabolic gene polymorphisms
Authors: Taioli Emanuela , Garte Seymour 
Published: October 2002

AbstractThe relationship between exposure and disease when biomarkers are introduced in an epidemiologic study is explored and summarized. In molecular epidemiologic studies, biologic measurements play a major role as markers of exposure, disease or susceptibility to disease and/or exposure. In this scenario, the definition and management of confounding factors may change. Sometimes the presence or activation of the biomarker is partially caused by the relevant environmental exposure, and therefore the 2 variables (exposure and biomarker) should not be always treated as confounders of each other. Models of exposure‐disease association in the presence of biologic markers are presented. The concept of confounders is reviewed in light of the role of biomarkers in the pathway between exposure and disease. © 2002 Wiley‐Liss, Inc.
Distinct in vivo expression patterns of survivin splice variants in renal cell carcinomas
Authors: Mahotka Csaba , Krieg Thomas , Krieg Andreas , Wenzel Michael , Suschek Christoph V. , Heydthausen Manfred , Gabbert Helmut E. , Gerharz Claus D. 
Published: October 2002

AbstractSurvivin, a novel member of the inhibitor of apoptosis protein (IAP) family, reduces the susceptibility of tumor cells to proapoptotic stimuli, thereby promoting tumor cell survival during tumor progression and treatment with anticancer drugs. Recently, we identified 2 novel alternative splice variants of survivin, survivin‐2B and survivin‐ΔEx3, which differ in their antiapoptotic properties. Survivin‐2B has lost its antiapoptotic potential and may act as a naturally occurring antagonist of antiapoptotic survivin and survivin‐ΔEx3. Because the in vivo expression of these splice variants in human cancer has not been analyzed so far, 57 renal cell carcinomas (RCCs) were explored using quantitative reverse transcriptase polymerase chain reaction. We found that all RCCs express survivin‐ΔEx3, survivin‐2B and survivin, the latter being the dominant transcript. When we compared early and intermediate stages with late stages of clear cell RCCs, no significant changes in the expression levels of survivin and survivin‐ΔEx3 became evident. However, a significant decrease was observed for the mRNA ratio between survivin‐2B and survivin in late tumor stages (p = 0.036). Chromophilic/papillary RCCs, which are known to be less aggressive than clear cell RCCs, did not show significantly lower expression levels of antiapoptotic survivin and survivin‐ΔEx3, compared with stage‐adjusted clear cell RCCs. Our study demonstrates for the first time in vivo expression of functionally different survivin variants and suggests a role of these survivin splice variants in the progression and clinical behavior of human RCCs. © 2002 Wiley‐Liss, Inc.
Targeting of the photocytotoxic compound AlPcS4 to hela cells by transferrin conjugated peg‐liposomes
Authors: Gijsens Antoon , Derycke Annelies , Missiaen Ludwig , De Vos Dirk , Huwyler Jörg , Eberle Alex , de Witte Peter 
Published: October 2002

AbstractPhotodynamic therapy has attracted increasing interest over the last few years, whereby the activation of photosensitizers by light causes the production of reactive oxygen species (ROS), such as singlet oxygen, which are cytotoxic. The goal of our study was to enhance the photodynamic activity of the photosensitizer aluminum phthalocyanine tetrasulfonate (AlPcS4) through its specific delivery to tumor cells. Since many tumor cells, among which are HeLa cells, overexpress the transferrin receptor, we synthesized transferrin conjugated PEG‐liposomes that contained AlPcS4 that could be internalized by receptor mediated endocytosis. The antiproliferative activity of the targeted liposomes was evaluated and compared to the native AlPcS4 and the non‐targeted liposome. These findings were supplemented with data on intracellular concentration of the photo‐active compounds. The accumulation together with ROS production after irradiation was visualized by using confocal microscopy to confirm the data found in the antiproliferative and accumulation assay. Tf‐Lip‐AlPcS4 was 10 times more photocytotoxic (IC50, 0.63 μM) than free AlPcS4 at a light dose of 45 kJ/m whereas Lip‐AlPcS4 displayed no photocytotoxicity at all. The high photocytotoxicity of Tf‐Lip‐AlPcS4 was shown to be the result of a high intracellular concentration (136.5 μM) in HeLa cells, which could be lowered dramatically by incubating the conjugate with a competing transferrin concentration. The images of intracellular accumulation and ROS production matched the accumulation and photocytotoxicity profile of the different photo‐active compounds. The photodynamic activity of the Tf‐Lip‐AlPcS4 conjugate on HeLa cells is much more potent than free AlPcS4 as a result of selective transferrin receptor mediated uptake. © 2002 Wiley‐Liss, Inc.
Novel products of the HUD, HUC, NNP‐1 and α‐internexin genes identified by autologous antibody screening of a pediatric neuroblastoma library
Authors: Behrends Uta , Jandl Thomas , Golbeck Anja , Lechner Brigitte , Müller‐Weihrich Stephan , Schmid Irene , Till Holger , Berthold Frank , Voltz Raymond , Mautner Josef M. 
Published: October 2002

AbstractAutologous serological screening of a cDNA expression library (SEREX) derived from childhood neuroblastoma led to the identification of 10 different antigens, including 6 novel gene products. The novel antigen 018INX was derived from a small open reading frame in a region of α‐internexin mRNA that was previously described as 3′ untranslated region. 018INX thus represents a novel type of tumor antigen. Five novel gene products were derived from NNP‐1 (NNP3) and Hu genes (HuC‐L, HuD3, HuDY, HuD1proc). As indicated by sequence analysis, these antigens were generated by alternative splicing and/or alternative promoter usage or allelic polymorphism. mRNA expression analyses revealed different tissue restrictions of novel compared to known HuD and NNP‐1 transcripts in normal and malignant tissues. The expressions patterns of distinct transcripts indicated potential clinical meanings as diagnostic and/or prognostic tissue markers. When kinetics of serum antibody titres against SEREX‐defined antigens were compared to tumor load over time in our patient with neuroblastoma, we found 100‐fold increases of anti‐Hu and anti‐018INX antibody titres preceding the clinical diagnosis of recurrent tumor growth after 2 years. When sera of pediatric patients with cancer (30) and healthy controls (30) were tested for humoral responses to SEREX‐defined neuroblastoma antigens, we detected antibodies against all known antigens and NNP3 with low frequencies and titres in control sera, while anti‐018INX and anti‐Hu antibodies were found in cancer patients only. Our findings indicate that SEREX‐defined tumor antigens might provide novel tools for understanding and treatment of this aggressive childhood malignancy. © 2002 Wiley‐Liss, Inc.
Recent thymic emigrants and prognosis in T‐ and B‐cell childhood hematopoietic malignancies
Authors: Petridou Eleni , Klimentopoulou Alexandra E. , Moustaki Maria , Kostrikis Leontios G. , Hatzakis Angelos , Trichopoulos Dimitrios ,   Hellenic Pediatric Hematology Oncology Group
Published: October 2002

AbstractThe concentration of T‐cell receptor rearrangement excision DNA circles (TRECs) in peripheral blood mononuclear cells (PBMCs) is currently known to be a marker of recent thymic emigrants. We evaluated the hypothesis that TREC values would be lower in childhood T‐cell hematopoietic malignancies than in childhood B‐cell acute lymphoblastic leukemia (ALL) or healthy controls because the former category may reflect compromised thymic function. From the Greek national childhood leukemia/lymphoma database we obtained all 30 available T‐cell leukemia/non‐Hodgkin's lymphoma cases, 30 age‐ and sex‐matched childhood B‐cell origin cases of ALL and 60 healthy hospital controls. We compared TREC levels in PBMCs using a real‐time PCR assay. There was highly significant reduction of TREC values in children with T‐cell malignancies (median 3,100 TRECs/106 PBMCs), whereas children with B‐cell origin ALL had slightly but nonsignificantly lower TREC values compared to healthy children (medians 19,300 and 22,500 TRECs/106 PBMCs, respectively). During a median follow‐up period of about 19 months, only 4 children died. All of them had a T‐cell hematopoietic malignancy and relatively low TREC values. The number of TRECs was higher among healthy girls than among healthy boys, and a similar pattern was evident in T‐cell malignancies. It appears that there is a pattern of concordance of high TREC values with better disease prognosis in hematologic childhood malignancies. This applies to specific disease entities with better prognosis (B‐cell origin ALL having higher TREC values than T‐cell leukemia/lymphoma) and to gender, another important predictor of prognosis conditional on disease entity (girls having higher TREC values than boys); however, it may also be true for the survival of individual patients. These preliminary findings can be used as hypothesis‐generating indications that should be confirmed in larger data sets. © 2002 Wiley‐Liss, Inc.
Inhibition of CD40 expression and CD40‐mediated dendritic cell function by tumor‐derived IL‐10
Authors: Shurin Michael R. , Yurkovetsky Zoya R. , Tourkova Irina L. , Balkir Levent , Shurin Galina V. 
Published: October 2002

AbstractAs CD40 plays a key role in both antitumor immunity and DC maturation, we have studied the regulation of its expression during DC hematopoiesis (dendropoiesis) in vitro and in vivo in the tumor microenvironment. Using MC38 colon adenocarcinoma tumor models, we have demonstrated that DCs generated in vitro from bone marrow precursors obtained from tumor‐bearers have significantly lower expression of CD40 molecules compared to DCs generated from tumor‐free mice. Furthermore, CD40 expression on DCs isolated from the spleens of tumor‐bearing mice was also significantly reduced, suggesting that tumor‐derived factors inhibit CD40 expression on DCs during dendropoiesis both in vitro and in vivo. Interestingly, CD40 ligation on DCs generated from tumor‐bearers did not result in inducible expression of IL‐12 protein or IL‐12 p40 mRNA. However, Staphylococcus aureus–induced IL‐12 production by DCs was not altered in tumor‐bearers, confirming that inhibition of IL‐12 production by DCs generated in vitro from tumor‐bearing mice was due to reduced expression of CD40 on DCs. We have also shown that MC38 tumor cells produce IL‐10 and that exogenous IL‐10 causes downregulation of CD40 expression on DCs. In addition, endogenous IL‐10 produced by colon carcinoma cells inhibited CD40‐dependent IL‐12 production by DCs since tumor‐induced inhibition of IL‐12 production was abrogated by neutralizing anti‐IL‐10 antibody. Finally, systemic administration of FLT3L and/or CD40L reversed CD40 and IL‐12 (p40) deficiency of DCs in tumor‐bearing mice in vivo. These findings thus demonstrate that tumor‐derived factors, including IL‐10, inhibit CD40 expression on DCs and DC precursors and suppress their maturation and function. © 2002 Wiley‐Liss, Inc.
Molecular analysis of lipid‐depleting factor in a colon‐26‐inoculated cancer cachexia model
Authors: Inadera Hidekuni , Nagai Shigenori , Dong Hong‐Yan , Matsushima Kouji 
Published: October 2002

AbstractCachexia in cancer is characterized by progressive emaciation involving depletion of host adipose tissue stores, the molecular mechanism of which remains largely unknown. In this study, we have attempted to clarify the biologic characteristics of lipid‐depleting factor in a mouse cachexia model. Utilizing differentiated 3T3‐L1 adipocytes, we established an assay method quantifying the lipid‐depleting activity in plasma derived from colon‐26‐inoculated mice and then analyzed the associated molecular mechanism. Injection (s.c.) of a mouse colon adenocarcinoma cell line, colon‐26 clone 20, induced cachexia, as evidenced by progressive weight loss. Addition of clone 20–derived cachexigenic, but not clone 5–derived noncachexigenic, plasma to the culture medium of differentiated 3T3‐L1 adipocytes reduced the TG content in cultured cells. The ability of the introduced plasma to induce TG loss in 3T3‐L1 cells paralleled the body weight changes of tumor‐inoculated host mice. Clone 20 plasma, but not clone 5 plasma or recombinant IL‐6, elicited lipolytic activity, which induced glycerol release from 3T3‐L1 cells. Addition of clone 20 plasma to cultured 3T3‐L1 adipocytes reduced TG synthesis from [14C]‐glucose compared to clone 5 plasma, indicating that the lipid‐depleting activity resulting from addition of clone 20 plasma depended not only on induction of lipolysis but also on inhibition of lipogenesis. Addition of clone 20 plasma to cultured 3T3‐L1 adipocytes reduced the quantity of mature SREBP‐1 in the nucleus of 3T3‐L1 cells without affecting PPAR‐γ and C/EBP‐α. Although TNF‐α induced apoptosis in 3T3‐L1 cells, clone 20 plasma did not. These results suggest that the lipid‐depleting factor in clone 20 plasma is different from either IL‐6 or TNF‐α, and that this factor interfered with not only lipolysis but also lipogenesis through SREBP‐1 of 3T3‐L1 adipocytes. © 2002 Wiley‐Liss, Inc.
Evaluation of DRAINMOD‐S for simulating water table management under semi‐arid conditions
Authors: Wahba M. A. S. , El‐Ganainy M. , Abdel‐Dayem M. S. , Kandil H. , Gobran Atef. 
Published: October 2002

AbstractThe water table management simulation model, DRAINMOD‐S, was evaluated under semi‐arid conditions using field data from the Maruit experimental field in the western delta of Egypt for three cropping seasons; maize 1999, wheat 1999/2000 and maize 2000. Two water table management systems (conventional drainage (FD) and controlled drainage (CD)) were applied in the study area. The recorded data included daily ground water table depths, drain outflows during flow events, soil salinity to depth of 1.20 m from the soil surface (0.30 m interval), and relative crop yield. DRAINMOD‐S was run to simulate the applied water table management systems for the same study periods. The reliability of the model was evaluated by comparing measured and predicted values of the daily ground water table depth, cumulative outflow based on total monthly outflow, soil salinity during each season, and relative crop yield. Good agreement was found between the measured and predicted values. DRAINMOD‐S predicted values within an absolute deviation ranged from 11.0 to 16.0 cm for ground water table depth, from 18 to 75 mm for drain outflows, from 0.22 to 1.08 dS m−1 for soil salinity, and from 4.62 to 4.86% for relative crop yield. The model showed the potential for long‐term simulation and planning of ground water table management systems under semi‐arid conditions of the western delta of Egypt. Copyright © 2002 John Wiley & Sons, Ltd.
Improvement of the functions of osteoblasts seeded on modified poly(D,L‐lactic acid) with poly(aspartic acid)
Authors: Cai Kaiyong , Yao Kangde , Hou Xin , Wang Yaquan , Hou Yongjiang , Yang Zhiming , Li Xiuqiong , Xie Huiqi 
Published: October 2002

AbstractOne of the challenges in the field of tissue engineering is the development of biomaterial/cell interactions. For the purposes of the present study, two molecular weights of poly(aspartic acid) (PASP) were used to modify poly(D,L‐lactic acid) (PDLLA) films in order to enhance their cell affinity. The properties of the PDLLA‐modified surfaces and the controls were investigated by water contact angle measurement and electron spectroscopy for chemical analysis (ESCA). These data reflect the change in the biocompatibility of modified PDLLA surfaces. Then rat osteoblasts were seeded onto these modified surfaces and on controls to examine their effects on cell adhesion and proliferation. Cell morphologies on these surfaces were studied by scanning electron microscopy (SEM), and cell viability was evaluated with a MTT assay. In addition, differentiated cell function was assessed by measuring alkaline phosphatase (ALP) activity. The results suggest that PASP‐modified surfaces may enhance the interactions between osteoblasts and PDLLA films. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 62: 283–291, 2002
Adsorbed poly(ethyleneoxide)–poly(propyleneoxide) copolymers on synthetic surfaces: Spectroscopy and microscopy of polymer structures and effects on adhesion of skin‐borne bacteria
Authors: Marsh Lorraine H. , Coke Mark , Dettmar Peter W. , Ewen Richard J. , Havler Michael , Nevell Thomas G. , Smart John D. , Smith James R. , Timmins Barry , Tsibouklis John , Alexander Cameron 
Published: October 2002

AbstractPoly(ethyleneoxide)–copoly(propyleneoxide) (PEO‐PPO) polymer coatings were evaluated for their resistance to the attachment of the marker organism Serratia marcescens and the skin‐borne bacteria Staphylococcus epidermidis. The copolymers were adsorbed onto poly(styrene) films—chosen as simplified physicochemical models of skin surfaces—and their surface characteristics probed by contact angle goniometry, attenuated total reflectance–Fourier transform infrared (ATR‐FTIR), atomic force microscopy (AFM), and X‐ray photoelectron spectroscopy (XPS). These functional surfaces were then presented to microbial cultures, bacterial attachment was assessed by fluorescence microscopy and AFM, and the structures of the polymer films examined again spectroscopically. Surface characterization data suggest that the adsorbed copolymer was partially retained at the surface and resisted bacterial attachment for 24 h. Quantitative evaluation of cell attachment was carried out by scintillation counting of 14C‐labeled microorganisms in conjunction with plate counts. The results show that a densely packed layer of PEO‐PPO copolymer can reduce attachment of skin commensals by an order of magnitude, even when the coating is applied by a simple adsorptive process. The work supports the hypothesis that adhesion of microorganisms to biological substrates can be reduced if a pretreatment with an appropriate copolymer can be effected in vivo. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 61: 641–652, 2002
Tribological investigation of oriented HDPE
Authors: Hoseini Mohammed , Lausmaa Jukka , Boldizar Antal 
Published: October 2002

AbstractThe possibility to control the wear properties of high‐density polyethylene (HDPE) material at an early processing stage is explored. Wear measurements of cold roll‐drawn HDPE with two different draw ratios were carried out for three sliding planes, each in two directions. The dependence of the wear properties on the degree and direction of orientation was investigated. The experiments were performed in a pin‐on‐disc machine in a dry environment. The tribo‐couple consisted of HDPE plates versus a standardised diamond coated steel disc. The results show that the wear resistance of cold roll‐drawn HDPE differ widely, by a factor up to 6, depending on the sliding direction relative to the drawing direction. The material has a significantly better wear resistance when the sliding direction was perpendicular to the processing direction. The best wear resistance was in the end plane and it was improved by a factor up to 3.6 when the draw ratio was increased from 2 to 4. These results indicate that molecular orientation by polymer processing is a promising method to improve the wear properties and decrease the wear debris production of HDPE. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 61: 634–640, 2002
Induction of olfactory mucosal and liver metabolism of lidocaine by 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin
Authors: Genter Mary Beth , Apparaju Sandhya , Desai Pankaj B. 
Published: October 2002

AbstractFormulation of drugs for administration via the nasal cavity is becoming increasingly common. It is of potential clinical relevance to determine whether intranasal drug administration itself, or exposure to other xenobiotics, can modulate the levels and/or activity of nasal mucosal metabolic enzymes, thereby affecting the metabolism and disposition of the drug. In these studies, we examined changes in several of the major metabolic enzymes in nasal epithelial tissues upon exposure to the environmental contaminant 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD), as well as the impact of these changes on the metabolism of a model intranasally administered drug, lidocaine. Results of these studies show that TCDD can induce multiple metabolic enzymes in the olfactory mucosa and that the pattern of induction in the olfactory mucosa does not necessarily parallel that which occurs in the liver. Further, increases in enzyme levels noted by Western blot analysis were associated with increased activities of several nasal mucosal enzymes as well as with enhanced conversion of lidocaine to its major metabolite, monoethyl glycine xylidide (MEGX). These results demonstrate that environmental exposures can influence the levels and activity of nasal mucosal enzymes and impact the pharmacology of drugs administered via the nasal route. © 2002 Wiley Periodicals, Inc. J Biochem Mol Toxicol 16:128–134, 2002. DOI 10.1002/jbt.10032
Progesterone attenuates the inhibitory effects of cardiotonic digitalis on pregnenolone production in rat luteal cells
Authors: Chen Jiann‐Jong , Chien Eileen Jea , Wang Paulus S. 
Published: October 2002

AbstractPrevious studies have shown that digoxin decreases testosterone secretion in testicular interstitial cells. However, the effect of digoxin on progesterone secretion in luteal cells is unclear. Progesterone is known as an endogenous digoxin‐like hormone (EDLH). This study investigates how digitalis affected progesterone production and whether progesterone antagonized the effects of digitalis. Digoxin or digitoxin, but not ouabain, decreased the basal and human chorionic gonadotropin (hCG)‐stimulated progesterone secretion as well as the activity of cytochrome P450 side chain cleavage enzyme (P450scc) in luteal cells. 8‐Br‐cAMP and forskolin did not affect the reduction. Neither the amount of P450scc, the amount of steroidogenic acute regulatory (StAR) protein, nor the activity of 3β‐hydroxysteroid dehydrogenase (3β‐HSD) was affected by digoxin or digitoxin. Moreover, in testicular interstitial and luteal cells, progesterone partially attenuated the reduction of pregnenolone by digoxin or digitoxin and the progesterone antagonist, RU486, blocked this attenuation. These new findings indicated that (1) digoxin or digitoxin inhibited pregnenolone production by decreasing the activity of P450scc enzyme, but not Na+–K+‐ATPase, resulting in a decrease on progesterone secretion in rat luteal cells, and (2) the inhibitory effect on pregnenolone production by digoxin or digitoxin was reversed partially by progesterone. In conclusion, digoxin or digitoxin decreased progesterone production via the inhibition of pregnenolone by decreasing P450scc activity. Progesterone, an EDLH, could antagonize the effects of digoxin or digitoxin in luteal cells. J. Cell. Biochem. 86: 107–117, 2002. © 2002 Wiley‐Liss, Inc.