bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular and functional MDR1‐Pgp and MRPs expression in human glioblastoma multiforme cell lines
Authors: Declèves Xavier , Fajac Anne , Lehmann‐Che Jacqueline , Tardy Marcienne , Mercier Claire , Hurbain Ilse , Laplanche Jean‐Louis , Bernaudin Jean‐François , Scherrmann Jean‐Michel
Published: August 2002

The aim of our study was to investigate the functional expression of P‐glycoprotein (Pgp) and multidrug resistance‐associated proteins (MRPs) in 2 distinct glioma cells (GL15 and 8MG) from patients with glioblastoma multiforme. MDR1 gene and Pgp expression was not detected in either cell line by RT‐PCR and Western blotting, respectively. In contrast, MRP1 was detected at both mRNA and protein level in both cell lines, with a higher expression in the 8MG cells that occur predominantly at the cell membrane. Three other MRPs (MRP3, MRP4 and MRP5) were detected by RT‐PCR in both cell lines, whereas MRP2 was not expressed. In addition, MRP3 protein was also detected by immunocytochemistry in both GL15 and 8MG cell lines. Indomethacin and probenecid, 2 modulators of MRPs activity, increased the accumulation of vincristine and etoposide, 2 substrates of MRPs, by both cell lines. These modulators also decreased the efflux of vincristine from both cell lines with a more pronounced effect in 8MG cells. In conclusion, our results show functional expression of MRPs leading to a decrease in the intracellular vincristine and etoposide concentrations in human glioblastoma cell lines. Furthermore, our results that exhibit protein expression of MRP1 and MRP3 and gene expression of MRP4 and MRP5 in these 2 glioblastoma cell lines suggest new mechanisms that could lead to a MDR phenotype of tumour cells in patients with glioblastoma multiforme. © 2002 Wiley‐Liss, Inc.
History of allergies among adults with glioma and controls
Authors: Wiemels Joseph L. , Wiencke John K. , Sison Jennette D. , Miike Rei , McMillan Alex , Wrensch Margaret
Published: August 2002

The causes of most adult gliomas are essentially unknown. Previous studies have indicated associations between immune system factors and the incidence of adult glioma, specifically that those individuals with certain allergic conditions may have decreased risk of glioma. We obtained detailed allergy histories for 405 adults newly diagnosed with glioma in the San Francisco Bay Area from 1997–1999 and 402 age‐gender‐ethnicity frequency‐matched population‐based controls. Seventy‐nine percent of eligible cases or their proxies and 74% of eligible controls completed in‐person interviews about allergies, age at onset, frequency, duration and severity. Overall, cases were less likely than controls to report any allergy (72% vs. 85%; odds ratio [OR] = 0.5 [0.3–0.7]); for self‐reported cases (n = 269), OR = 0.7 (0.4–0.97) and for proxy‐reported cases, OR = 0.3 (0.2–0.5). Pollen, dairy and nut allergies were significantly less common in cases than controls and most other allergens had odds ratios of less than one. There were no apparent trends with numbers of symptoms, route of exposure of allergen or reported severity of allergy, but there was a significant dose‐response with increasing numbers of allergens (p < 0.0001 for linear trend among all cases vs. controls and p = 0.02 among self‐reported cases only vs. controls). Although our work displays strong and consistent associations, future efforts must attempt to establish whether an immune system typified by proclivity to allergies, or an immunologic consequence of the allergies themselves, might be capable of preventing nascent brain tumors. The dominance of humoral immunity in the central nervous system is consistent with either of these models. Alternatively, common genetic or environmental causes for allergies and gliomagenesis may mediate or confound these observed inverse risks for allergies and gliomas, or other explanations may exist. Future work might reveal an important role for immunologic factors in gliomagenesis and potential preventative and/or therapeutic modalities. © 2002 Wiley‐Liss, Inc.
Changing face and different countenances of prostate cancer: Racial and geographic differences in prostate‐specific antigen (PSA), stage, and grade trends in the PSA era
Authors: Jani Ashesh B. , Vaida Florin , Hanks Gerald , Asbell Suscha , Sartor Oliver , Moul Judd W. , Roach Mack , Brachman David , Kalokhe Urmi , Muller‐Runkel Renate , Ray Paul , Ignacio Lani , Awan Azhar , Weichselbaum Ralph R. , Vijayakumar Srinivasan
Published: August 2002

The purpose of this investigation was to examine changes in pretreatment prostate‐specific antigen (PSA), stage, and grade over the past decade as a function of race and geographic region. A multiinstitutional database representing 6,790 patients (1,417 African‐American, 5,373 white) diagnosed with nonmetastatic prostate cancer between 1988 and 1997 was constructed. PSA, stage, and grade data were tabulated by calendar year and region, and time trend analyses based on race and region were performed. There was an overall decline of PSA of 0.8%/year, which was significant (P = 0.0001), with a faster rate of decline in African‐Americans (1.9%/year) than for whites (0.6%/year). The odds ratio (OR) for a stage shift was 1.09, which was significant (P < 0.0001), and this shift was greater in whites. The OR for an overall grade shift was 1.15, which was significant (P < 0.0001). Although grade and PSA trends were similar for the different regions, there were significant regional differences in stage trends. The implications are that the face of prostate cancer has changed over the past decade; i.e., the distributions of stage, grade, and PSA (the most important prognosticators) have changed. In addition, the countenances of that face are different for whites and African‐Americans. For African‐Americans, this is good news: the stage, grade, and PSA distributions are more favorable now than before. For whites, the trends are more complex and more dependent on region. These findings should be used for future clinical and health‐policy decisions in the screening and treatment of prostate cancer. © 2001 Wiley‐Liss, Inc.
Recreational physical activity and ovarian cancer in a population‐based case‐control study
Authors: Bertone Elizabeth R. , Newcomb Polly A. , Willett Walter C. , Stampfer Meir J. , Egan Kathleen M.
Published: August 2002

Results from epidemiologic studies of physical activity and ovarian cancer have been inconsistent, with 2 prospective studies reporting a modest positive association. We evaluated this relationship in a population‐based case‐control study conducted in Massachusetts and Wisconsin. Incident cases diagnosed between 1991 and 1994 were identified through statewide tumor registries. Community controls were selected randomly from lists of licensed drivers and Medicare recipients. Participation in moderate and vigorous recreational physical activity at age 12, age 20 and 5 years prior to diagnosis was assessed by telephone interview. Data were available for 327 cases and 3,129 controls. Results were adjusted for age, parity and other ovarian cancer risk factors. Total and vigorous physical activity were not associated with a substantial decrease in ovarian cancer risk at any age. The relative risk (RR) for women reporting ≥ 7 vs. 0 hr/week of recent vigorous activity was 0.85 [95% confidence interval (CI) = 0.39–1.86; p for trend = 0.31]. When metabolic equivalent task (MET) hours of activity were estimated, only women in the highest category had any reduction in risk (RR for > 42 MET‐hours/week at the reference age = 0.70; 95% CI = 0.36–1.35; p for trend = 0.41). Overall, our results provide only limited support for an inverse association between recreational physical activity and risk of ovarian cancer. © 2002 Wiley‐Liss, Inc.
Enhancement of colorectal tumor targeting using a novel biparatopic monoclonal antibody against carcinoembryonic antigen in experimental radioimmunoguided surgery
Authors: Kim Jin C. , Roh Seon A. , Koo Kum H. , Ryu Jang H. , Hong Hyun K. , Oh Seung J. , Ryu Jin S. , Kim Ho J. , Bodmer Walter F.
Published: August 2002

Biparatopic CEA, carcinoembryonic antigen (MAb) was newly designed and tested as to whether it enhanced the accuracy of tumor detection by reducing non‐specific binding in experimental radioimmunoguided surgery. Biparatopic MAb was prepared by using cross‐linking of reduced Fab′ fragments from PR1A3 and T84.66. Fifty‐nine tumors from 2 human colorectal carcinoma cell lines with high (KM‐12c) and low (Clone A) carcinoembryonic antigen (CEA) expression were successfully implanted subcutaneously on the backs of 42 nude mice. Tumors were localized using 125I‐labeled MAbs: IgG, F(ab′)2 and Fab′ of PR1A3, and biparatopic MAb of PR1A3 and T84.66. Radioactivity counted on a portable radioisotope detector correlated well with that counted on a gamma counter (p < 0.001). Accumulations of radioactivity in control mice without tumorigenesis were the greatest in PR1A3 IgG‐pretreated mice and the least in biparatopic MAb‐pretreated mice. Tumors of 2 cell lines did not differ in the distribution of radiolabeled MAbs. Localization indices of the tumor in various organs revealed 1.3 to 4.1 in PR1A3 IgG‐pretreated mice, 2.4 to 6.6 in fragment MAbs of PR1A3‐pretreated mice and 2 to 4.6 in biparatopic MAb‐pretreated mice. Silver grains and immune staining were predominantly distributed in tumor cells of all types of MAb‐pretreated mice. Sensitivity and specificity of tumor localization by radioimmunoguided surgery (RIGS) were the highest in the biparatopic MAb‐pretreated mice (90.9% and 94.5%, respectively) and the least in the PR1A3 IgG‐pretreated mice (50% and 72%). The biparatopic MAb using 2 anti‐CEA MAbs against different epitopes achieved a great affinity and avidity with accurate localization of colorectal carcinoma in experimental radioimmunoguided surgery. © 2001 Wiley‐Liss, Inc.
Monetary policy transparency, inflation and the sacrifice ratio
Authors: Chortareas Georgios , Stasavage David , Sterne Gabriel
Published: August 2002

We examine how inflation and the costs associated with disinflation episodes are related to monetary policy transparency. We develop a simple model that demonstrates how transparency may result in lower inflation. Our empirical results show that in general, transparency may be associated with lower inflation across a broad range of countries and frameworks. In addition, the output costs of disinflation, as measured by the sacrifice ratio, are negatively related to the degree of monetary policy transparency. The capacity of the central bank to limit the monetary financing of government deficits also has an inflation‐reducing effect. Considering transparency as a possible determinant of cross‐country differences in the costs of disinflation represents a new contribution to the literature, especially given the failure of previous empirical research to find a robust negative relationship between other aspects of the central bank's institutional design and the sacrifice ratio. Copyright © 2002 John Wiley & Sons, Ltd.
Temperament and behavioral problems among infants in alcoholic families
Authors: Peterson Edwards Ellen , Leonard Kenneth E. , Eiden Rina Das
Published: August 2002

This study examined the association between paternal alcoholism and 12‐month infant temperament and 18‐month behavior problems. The role of associated parental psychopathology and maternal drinking in exacerbating risk for maladaptive behavioral outcomes was also examined. Participants were 213 families (102 control families, 94 paternal alcoholic families, and 17 families with alcoholic fathers and heavy drinking mothers) who were assessed when their child was 12 months old and reassessed again when their child was 18 months old. Infants of alcoholics displayed marginally more stubborn/persistent temperaments at 12 months of age, but significantly more internalizing problems at 18 months. Analyses suggested that internalizing problems in the infants of alcoholics could be attributed to the paternal depression concomitant with paternal alcoholism. In addition, an interaction was observed, indicating that paternal alcohol problems predicted 18‐month externalizing problems among families with low maternal depression, but not among families with high maternal depression. Children of depressed mothers exhibited uniformly higher externalizing scores, but were not further impacted by paternal alcohol problems. However, children of nondepressed mothers were adversely affected by fathers' drinking as reflected by higher externalizing behavior scores. The results highlight the necessity of addressing the overall contextual risks that occur with paternal alcoholism in studies of the development of children in alcoholic families. © 2001 Michigan Association for Infant Mental Health.
Inhibition and recovery of maternal and fetal cholinesterase enzyme activity following a single cutaneous dose of methyl parathion and diazinon, alone and in combination, in pregnant rats
Authors: Abu‐Qare Aqel W. , Abou‐Donia Mohamed B.
Published: August 2002

Pregnant Sprague‐Dawley rats (14–18 days of gestation) were treated with a single cutaneous subclinical dose(s) of 10 mg kg−1 (15% of LD50) of methyl parathion (O,O‐dimethyl O‐4‐nitrophenyl phosphorothioate) and 65 mg kg−1 (15% of LD50) of diazinon (O,O)‐diethyl O‐2‐isopropyl‐6‐methylpyrimidinyl phosphorothioate, and their combination. Animals were sacrificed at 1, 2, 4, 12, 24, 48, 72, and 96 h after dosing. Inhibition of maternal and fetal cholinesterase enzyme activity has been determined. Methyl parathion significantly inhibited maternal and fetal brain acetylcholinesterase (AChE) and plasma butyrylcholinesterase (BuChE) activity within 24 h after dosing. Diazinon and a mixture of methyl parathion and diazinon caused lesser inhibition compared with methyl parathion alone. Recovery of maternal and fetal brain AChE activity was in the order of diazinon > combination of diazinon and methyl parathion > methyl parathion 96 h after dosing. Although fetal plasma BuChE activity recovered to 100% of control within 96 h of application, maternal BuChE activity remained inhibited to 55% and 32% of control 96 h after application of methyl parathion and a mixture of methyl parathion and diazinon, respectively. Following a single dermal dose of methyl parathion, the activity of maternal liver BuChE was 63% of control 2 h after dosing, whereas inhibition of placental AChE or BuChE activity occurred 12 and 1 h following a single dose of methyl parathion, corresponding to activities of 63% and 54% of control, respectively. Diazinon, alone or in combination with methyl parathion, did not inhibit significantly the maternal liver BuChE or placental AChE and BuChE activity. The results suggest that dermal application of a single dose of methyl parathion and diazinon, alone or in combination, has an easy access into maternal and fetal tissues, resulting in inhibition of cholinesterase enzymes. The lower inhibitory effect of the combination of methyl parathion and diazinon might be due to competition of diazinon with methyl parathion for cytochrome P‐450 enzymes, resulting in formation of the potent cholinesterase inhibitor methyl paraoxon. The faster recovery of fetal cholinesterase enzymes is attributed to the rapid de novo synthesis of cholinesterase fetal tissues compared with the mother. Copyright © 2001 John Wiley & Sons, Ltd.
Hemocompatibility of materials used in microelectromechanical systems: Platelet adhesion and morphology in vitro
Authors: Weisenberg Brian A. , Mooradian Daniel L.
Published: August 2002

Microelectromechanical systems (MEMS) create an opportunity for the development of smaller, cheaper, and more precise biomedical instrumentation and devices. Little is known, however, about the hemocompatibility of the materials used to fabricate these devices. Because of the potentially harmful consequences of thrombus formation, a better understanding of blood interactions with bioMEMS materials is desirable. This study is an in vitro assessment of the hemocompatibility of silicon (Si), silicon dioxide (SiO2), silicon nitride (Si3N4), low‐stress silicon nitride (Si1.0N1.1), SU‐8 photoresist, and parylene thin films. A polycarbonate‐based polyurethane, was used as a reference material. Experiments were carried out to detect differences in platelet adhesion or morphology after contact with these materials under static conditions. Platelet adhesion on Si, Si3N4, Si1.0N1.1, and SU‐8 photoresist was significantly greater (P < 0.05) than platelet adhesion on polyurethane. Adhesion on parylene and SiO2 was not significantly different from on polyurethane (P < 0.05). The median platelet area and circularity were higher on polyurethane than all other materials. Materials that showed higher levels of platelet adhesion tended to have platelets that showed less spreading, except for SiO2, where platelets exhibited relatively low adhesion and spreading. This data suggests that Si, Si3N4, Si1.0N1.1, and SU‐8 photoresist may be more reactive to platelets and therefore more thrombogenic than parylene, SiO2, and polyurethane. These results may be helpful in guiding the selection of materials for use in the development of blood‐contacting microelectromechanical systems. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 60: 283–291, 2002; DOI 10.1002/jbm.10076
Heparin‐like polymers modulate proinflammatory cytokine production by lipopolysaccharide‐stimulated human monocytes
Authors: Anastase‐Ravion Sylvie , Carreno Marie‐Paule , Blondin Catherine , Ravion Olivier , Champion Jacqueline , Chaubet Frédéric , Haeffner‐Cavaillon Nicole , Letourneur Didier
Published: August 2002

The search for heparin‐like materials remains an intensive field of research. In this context, we studied the immunomodulatory properties of semisynthetic dextran derivatives and naturally occurring sulfated polysaccharides present in brown seaweed (fucans). In this study, we investigated the functional potencies of fucan and dextran derivatives by analyzing their effects on the release of proinflammatory cytokines by resting or lipopolysaccharide (LPS)‐stimulated human monocytes and their interactions on monocyte surfaces. The results showed that fucan, dextran derivatives, and heparin differentially (1) triggered interleukin‐1α, tumor necrosis factor α, interleukin‐6, and interleukin‐8 production by monocytes in a dose‐dependent manner, (2) modulated cytokine production by LPS‐stimulated monocytes, and (3) specifically inhibited the binding of biotinylated LPS to monocyte membranes. Taken together, these data indicated that fucan and dextran derivatives displayed interesting immunomodulatory effects on human blood cells that could be relevant as new drugs or biomaterial coatings. Indeed, such polysaccharides, by regulating monocyte activation, could contribute to the improved biocompatibility of implants. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 60: 375–383, 2002; DOI 10.1002/jbm.10112
Stress influence on interface in plasma‐sprayed hydroxyapatite coatings on titanium alloy
Authors: Millet P. , Girardin E. , Braham C. , Lodini A.
Published: August 2002

During clinical use of hydroxyapatite‐coated implants, mechanical stresses are added to pre‐existing residual stresses. The magnitude of these stresses affects the coating's performance. In this work we studied, by neutron diffraction and conventional X‐ray diffraction methods, the macrostresses induced by a plasma‐spraying process in the coating and at the interface. Neutron diffraction is one of the most suitable techniques for studying the strain distribution in a bulk material. X‐ray diffraction was used to determine residual stress in the hydroxyapatite coating. Using a neutron diffraction method at the nearest point to the interface, we saw no real difference between the stress observed on coated and that on non‐coated samples. With the X‐ray diffraction method, it appeared that the stress level was compressive on every sample. The major advantage of the neutron diffraction method is that measurements can be made on a thick coating in a nondestructive way. The disadvantage is the large‐gauge volume that we had to use because of the relatively low intensity of the neutron beam. Polishing is necessary for measurements inside the material when using the X‐ray method. This destructive method may alter the stress field of the deposit. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 60: 679–684, 2002
Surface micromechanics of ultrahigh molecular weight polyethylene: Microindentation testing, crosslinking, and material behavior
Authors: Gilbert Jeremy L. , Cumber Jeffrey , Butterfield Aaron
Published: August 2002

The wear behavior of ultrahigh molecular weight polyethylene (UHMWPE) is critical to the success of total joint replacements. Recent attempts to modify the wear behavior of UHMWPE by processing, in particular, crosslinking UHMWPE have shown promise to increase wear resistance, but concerns persist regarding other mechanical properties. It is also unclear what specific surface mechanical properties govern the wear resistance seen in these materials. The goal of this study was to demonstrate a custom‐built surface mechanical test system and method that measures the micromechanical response of microtomed UHMWPE surfaces to depth‐sensing microindentation tests. The surface structure of these UHMWPE materials was also examined using scanning electron microscopy and atomic force microscopy. A custom designed microindentation test system assessed the microindentation behavior of three UHMWPE resins: 1. Hylamer™, 2. GUR‐1020 CMS, and 3. Marathon™—a lightly crosslinked material. The effects of material and indentation depth were studied. Microindentation tests were performed with indentation depths ranging from 2 to 45 μm. Four different measurements of surface micromechanical behavior were obtained including the surface modulus, microhardness, hysteresis energy (irreversible work done to the sample per unit cycle) and its associated energy dissipation factor, and loading slope. Statistically significant differences in each of these parameters were found for each material. Generally, Hylamer had the largest values for these parameters, followed by the GUR resin and then the Marathon. Surface modulus was independent of depth of testing and found to be 651 MPa for Marathon, 738 MPa for GUR, and 1015 MPa for Hylamer (Modulus for bulk UHMWPE is 540 MPa for Hylamer, 620 for GUR, and 1380 for Hylamer). The microhardness varied between 67 and 162 MPa depending on material and depth of testing. Surface structural characterization shows that the microtoming process for surface preparation generated distinct surface features that varied between materials. Intermittent drawn ribbons of polymer with oriented crystals were observed in both scanning electron microscopy and atomic force microscopy. The surface density and size of these features were characteristic of the materials with the Hylamer having the fewest, but largest ribbons, followed by GUR and then Marathon. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 61: 270–281, 2002
Quantitative analysis of mRNA expression of TIMPs in the periprosthetic interface tissue of loose hips by real‐time PCR system
Authors: Sasaki Kan , Takagi Michiaki , Mandelin Jami , Takei Isao , Santavirta Seppo , Ida Hideo , Ogino Toshihiko , Konttinen Yrjö T.
Published: August 2002

Matrix metalloproteinases (MMPs) and their endogenous inhibitors, tissue inhibitors of metalloproteinases (TIMPs), have been reported to play a critical role in extracellular degradation around artificial hip joints. Although messenger ribonucleic acid (mRNA) expression patterns of several MMPs and TIMPs were reported, there is no report of quantitative mRNA analysis of TIMPs in periprosthetic tissues. In this study, mRNA expression of four different types of TIMPs in periprosthetic interface tissue of loose hips was analyzed by a quantitative polymerase chain reaction system. The mRNA expression level of TIMP‐1, ‐2, and ‐3 in periprosthetic interface tissue was significantly higher than that in control. In contrast, the mRNA expression level of TIMP‐4 in the periprosthetic interface tissue was lower. This study suggested that increased levels of TIMP‐1, ‐2, and ‐3, and decreased levels of TIMP‐4 may contribute to pathologic extracellular matrix degradation in combination with MMPs, thus leading to prosthetic loosening and osteolysis around artificial total hip joints. © 2001 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 58: 605–612, 2001
Peroxisome proliferator perfluorodecanoic acid alters glutathione and related enzymes
Authors: Chen Li‐Chuan , Tatum Vickie , Glauert Howard P. , Chow Ching K.
Published: August 2002

Previously we have shown that treatment with the peroxisome proliferator perfluorodecanoic acid (PFDA) significantly increased hepatic reduced glutathione (GSH) content without altering the activity of selenium‐glutathione peroxidase. In this study we examined some potential mechanisms by which PFDA treatment increases GSH levels. Male Sprague‐Dawley rats were given a single injection of 0, 8.8, 17.5, and 35 mg PFDA in corn oil per kg body weight.
Twelve days later the effects of PFDA on the activities of enzymes associated with GSH synthesis, utilization, and regeneration were assessed. The results showed that in a dose‐dependent manner, PFDA treatment significantly decreased the activity of γ‐glutamylcysteine synthetase, while the activities of NADPH‐generating enzymes, malic enzyme, glucose‐6‐phosphate dehydrogenase, and 6‐phosphogluconate
dehydrogenase were increased. PFDA treatment also dose dependently decreased cytosolic, but not microsomal, glutathione S‐transferase activity, and the activity of glutathione reductase was decreased by the
highest dose of PFDA. The data obtained suggest that increased hepatic GSH levels following PFDA treatment may result from increased regeneration and/or decreased utilization. © 2001 John Wiley & Sons, Inc. J Biochem Mol Toxicol 15:107–113, 2001
Patients with thrombotic thrombocytopenic purpura commonly develop metabolic alkalosis during therapeutic plasma exchange
Authors: Marques Marisa B. , Huang Shu T.
Published: August 2002

Thrombotic thrombocytopenic purpura (TTP) and myasthenia gravis (MG) are category I indications for therapeutic plasma exchange (TPE). This study was based on the hypothesis that the development of metabolic alkalosis during TPE is more common in TTP than in MG, based on our previous observations. In order to test it, we compared the levels of bicarbonate and potassium in both groups of patients undergoing plasmapheresis. Fifteen patients with TTP (190 procedures) and ten MG patients seen concurrently were studied. While baseline bicarbonate levels were similar among all patients, the post‐procedure bicarbonate levels in TTP patients were mostly elevated with a mean ± SD of 29.4 ± 3.5 mEq/L, as opposed to decreased or unchanged in MG patients 26.3 ± 3.1 mEq/L (mean ± SD) (P = 1.4 × 10−8). Furthermore, alkalosis in the TTP group persisted throughout subsequent daily treatments. There was also a significant decrease between pre‐ and post‐TPE potassium levels in TTP patients (P = 3 × 10−21) by paired Student's t test. Additionally, samples with levels <3.3 mEq/L were alkalotic 75% of the time. In the MG group, however, potassium was normal in 85% and 83% of the pre‐ and post‐TPE samples, respectively. Consequently, the hypokalemia was significantly more marked in the TTP group (P = 0.0008). These data confirm that plasmapheresis commonly induces metabolic alkalosis in TTP patients, probably due to high citrate in fresh frozen plasma, the frequency of treatments, and perhaps decreased renal clearance due to disease involvement of the kidneys. J. Clin. Apheresis. 16:120–124, 2001. © 2001 Wiley‐Liss, Inc.
Mapping of functional epitopes of osteopontin by monoclonal antibodies raised against defined internal sequences
Authors: Kon Shigeyuki , Yokosaki Yasuyuki , Maeda Masahiro , Segawa Tatsuya , Horikoshi Yuko , Tsukagoshi Hiroe , Rashid Mohammod M. , Morimoto Junko , Inobe Manabu , Shijubo Noriharu , Chambers Ann F. , Uede Toshimitsu
Published: August 2002

Osteopontin (OPN) is a secreted protein that has been implicated in diverse physiological and pathological processes. OPN can bind to integrins, via GRGDS or SVVYGLR amino acid sequences, and to other cell surface receptors, and many of OPN's functions are likely mediated via cell adhesion and subsequent signaling. Here we developed and characterized a series of five monoclonal antibodies, raised to distinct internal peptide sequences of human OPN, and have used these sequence‐specific reagents, along with the previously described anti‐OPN monoclonal antibody mAb53, to map functional epitopes of OPN that are important to cell adhesion and migration. All antibodies were reactive with native as well as recombinant human OPN. One antibody (2K1) raised against the peptide VDTYDGRGDSVVYGLRS could inhibit RGD‐dependent cell binding to OPN, with an efficacy comparable to that of mAb53. Furthermore, 2K1 could inhibit α9 integrin‐dependent cell binding to OPN. The epitope recognized by 2K1 was not destroyed by thrombin digestion, whereas mAb53 has been shown to be unable to react with OPN following thrombin cleavage. The two distinct epitopes defined by 2K1 and mAb53 antibodies are closely related to the SVVYGLR cell‐binding domain and the GLRSKS containing thrombin cleavage site, respectively, and are involved in cell binding and cell migration. J. Cell. Biochem. 84: 420–432, 2002. © 2001 Wiley‐Liss, Inc.
Nucleolin is a calcium‐binding protein
Authors: Gilchrist James S.C. , Abrenica Bernard , DiMario Patrick J. , Czubryt Michael P. , Pierce Grant N.
Published: August 2002

We have purified a prominent 110‐kDa protein (p110) from 1.6 M NaCl extracts of rat liver nuclei that appears to bind Ca2+. p110 was originally identified by prominent blue staining with ‘Stains‐All’ in sodium dodecyl sulfate–polyacrylamide gels and was observed to specifically bind ruthenium red and 45Ca2+ in nitrocellulose blot overlays. In spin‐dialysis studies, purified p110 saturably bound approximately 75 nmol Ca2+/mg protein at a concentration of 1 mM total Ca2+ with half‐maximal binding observed at 105 μM Ca2+. With purification, p110 became increasingly susceptible to proteolytic (likely autolytic) fragmentation, although most intermediary peptides between 40 and 90 kDa retained “Stains‐All”, ruthenium red, and 45Ca2+ binding. N‐terminal sequencing of intact p110 and a 70‐kDa autolytic peptide fragment revealed a strong homology to nucleolin. Two‐dimensional sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS–PAGE)/IEF revealed autolysis produced increasingly acidic peptide fragments ranging in apparent pI's from 5.5 for intact p110 to 3.5 for a 40 kDa peptide fragment. Intact p110 and several peptide fragments were immunostained with a highly specific anti‐nucleolin antibody, R2D2, thus confirming the identity of this protein with nucleolin. These annexin‐like Ca2+‐binding characteristics of nucleolin are likely contributed by its highly acidic argyrophilic N‐terminus with autolysis apparently resulting in largely selective removal of its basic C‐terminal domain. Although the Ca2+‐dependent functions of nucleolin are unknown, we discuss the possibility that like the structurally analogous HMG‐1, its Ca2+‐dependent actions may regulate chromatin structure, possibly during apoptosis. J. Cell. Biochem. 85: 268–278, 2002. © 2002 Wiley‐Liss, Inc.
Soluble osteopontin inhibits apoptosis of adherent endothelial cells deprived of growth factors*
Authors: Khan S.A. , Lopez‐Chua C.A. , Zhang J. , Fisher L.W. , Sørensen E.S. , Denhardt D.T.
Published: August 2002

Osteopontin (OPN) is primarily an extracellular glycosylated phosphoprotein capable of stimulating cell migration and cell attachment, predominantly to mineralized surfaces. Found in moderate levels in plasma, it acts as a cytokine able to modify gene expression via integrins and certain CD44 isoforms. In this work we show that soluble OPN inhibits apoptosis of adherent human umbilical vein endothelial cells incubated in medium lacking critical growth factors and cytokines. In a dose‐dependent manner OPN reduced the formation of apoptotic bodies and suppressed DNA fragmentation. OPN also caused an increase in Bcl‐XL mRNA levels, suppressed the apparent dispersion of Bcl‐XL throughout the cytoplasm, and slightly enhanced IκB‐α protein degradation. These data suggest that a function of OPN in homeostatic processes is to facilitate the survival of stressed endothelial cells, possibly by occupying unligated integrins and suppressing integrin‐mediated death. J. Cell. Biochem. 85: 728–736, 2002. © 2002 Wiley‐Liss, Inc.
Small GTP‐binding proteins in the nuclei of human placenta
Authors: Phillips Phoebe , Thomson Murray
Published: August 2002

Mitochondria and crude nuclei containing fractions from human placenta have been shown to contain proteins which bind [α32P]‐GTP. Prior to this study the number of GTP‐binding proteins in placental nuclei and their nucleotide specificity was not known. Also unknown was the identity of any of the GTP‐binding proteins in mitochondria of human placenta. Nuclei and mitochondria were purified from human placental extracts by sedimentation. Proteins were separated by electrophoresis and transferred to nitrocellulose membranes. Overlay blot with [α32P]‐GTP identified two nuclei proteins with approximate molecular weights of 24 and 27 kDa. Binding of [α32P]‐GTP to the 27 and 24 kDa proteins was significantly displaced by guanine nucleotides but not by adenine, thymine or cytosine nucleotides or deoxy (d) GTP. Western blot with a specific antibody to Ran identified a band at 27 kDa in nuclei and in mitochondrial fractions. These data indicate that both nuclei and mitochondria contain 24 and 27 kDa GTP‐binding proteins. The GTP‐binding proteins in nuclei display binding specificity for guanine nucleotides and the hydroxylated carbon 2 on the ribose ring of GTP appears essential for binding. It will be important in future studies to determine the functions of these small GTP‐binding proteins in the development and physiology of the placenta. J. Cell. Biochem. 84: 100–107, 2002. © 2001 Wiley‐Liss, Inc.
Is there a unique melting temperature for two‐state proteins?
Authors: Klimov D. K. , Thirumalai D.
Published: August 2002

Thermal unfolding (or folding) in many proteins occurs in an apparent two‐state manner, suggesting that only two states, unfolded and folded, are populated. At the melting temperature, Tm, the two states coexist. Using lattice models with side chains we show that individual residues become structured at temperatures that deviate from Tm, which implies that partially folded conformations make substantial contribution to thermodynamic properties of two‐state proteins. We also find that the folding cooperativity for a given residue is linked to its accessible surface area. These results are consistent with the experiments on GCN4‐like zipper peptide, which showed that local melting temperatures differ from Tm. Analysis of thermal unfolding of six proteins shows that ΔT/Tm∼N−1, where ΔT is the transition width and N is the number of residues. This scaling allows us to conclude that, when corrected for finite size effects, folding cooperativity can be captured using coarse grained models. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 161–165, 2002
MM3 parameterization for the BN dative bond
Authors: Fisher Luke , Holme Thomas
Published: August 2002

A number of compounds that contain the BN dative bond have been found to exhibit intriguing physiological activities. Although there is no proven mechanism for this activity, one hypothesis is that some form of borane transfer reaction occurs. In this scenario, the BN dative bond within the small molecule, putative pharmacore breaks, and the borane forms a new dative bond with a Lewis base site on some critical protein. For this hypothesis to be investigated further from a computational perspective, an improved MM3 parameter set for tetravalent Btetravalent N bonds has been developed and is reported here. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 913–922, 2001
Combined QM/MM study of the opsin shift in bacteriorhodopsin
Authors: Rajamani Ramkumar , Gao Jiali
Published: August 2002

Combined quantum mechanical and molecular mechanical (QM/MM) calculations and molecular dynamics simulations of bacteriorhodopsin (bR) in the membrane matrix have been carried out to determine the factors that make significant contributions to the opsin shift. We found that both solvation and interactions with the protein significantly shifts the absorption maximum of the retinal protonated Schiff base, but the effects are much more pronounced in polar solvents such as methanol, acetonitrile, and water than in the protein environment. The differential solvatochromic shifts of PSB in methanol and in bR leads to a bathochromic shift of about 1800 cm−1. Because the combined QM/MM configuration interaction calculation is essentially a point charge model, this contribution is attributed to the extended point‐charge model of Honig and Nakanishi. The incorporation of retinal in bR is accompanied by a change in retinal conformation from the 6‐s‐cis form in solution to the 6‐s‐trans configuration in bR. The extension of the π‐conjugated system further increases the red‐shift by 2400 cm−1. The remaining factors are due to the change in dispersion interactions. Using an estimate of about 1000 cm−1 in the dispersion contribution by Houjou et al., we obtained a theoretical opsin shift of 5200 cm−1 in bR, which is in excellent agreement with the experimental value of 5100 cm−1. Structural analysis of the PSB binding site revealed the specific interactions that make contributions to the observed opsin shift. The combined QM/MM method used in the present study provides an opportunity to accurately model the photoisomerization and proton transfer reactions in bR. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 96–105, 2002
Comparison of non‐diglyceride‐ and diglyceride‐based assays for pancreatic lipase activity
Authors: Steinhauer Jon R. , Hardy Robert W. , Robinson C. Andrew , Daly Thomas M. , Chaffin Carolyn , Konrad Robert J.
Published: August 2002

Pancreatic lipase is produced and stored in pancreatic acinar cells, and is normally secreted into the duct system. In disorders that cause pancreatic damage, pancreatic lipase enters the circulation, and serum lipase activity becomes useful in the diagnosis and evaluation of pancreatitis. During the last decade, many lipase assays have used the Imamura method, in which a series of enzymatic reactions utilizing a diglyceride substrate leads to the formation of a colorimetrically detected product. Historically, this method has been prone to significant interference from various substances, including glycerol itself. In the light of these limitations, we evaluated an automated enzymatic rate assay that uses a non‐diglyceride‐based, pancreatic lipase‐specific substrate. Precision, linearity, and potential interference were assessed, and when compared to the Imamura method, the non‐diglyceride‐based assay exhibited a slope of 0.475, y‐intercept of 15.89, r‐value of 0.9516, and Sy,x of 12.96. Similar results were also observed when the two assays were compared using samples with markedly elevated creatinine levels. Between‐day coefficients of variance (CVs) ranged from 5.0% to 5.5%, which compared well with the diglyceride‐based method, and linearity spanned a range of 3–156 U/L. Evaluation of over 2,000 patient results collected during a 6‐month period suggested that the manufacturer’s upper reference limit of 51 U/L may be too conservative. No significant interference was identified with bilirubin, triglyceride, or glycerol itself, and significant interference from hemoglobin was observed only at concentrations of 116 mg/dL or greater. As a result, the non‐diglyceride‐based method provides an acceptable alternative for the routine laboratory measurement of lipase activity. J. Clin. Lab. Anal. 16:52–55, 2002. © 2002 Wiley‐Liss, Inc.
Increased sialylation of polymeric λ‐IgA1 in patients with IgA nephropathy
Authors: Leung Joseph C.K. , Tang Sydney C.W. , Chan Daniel T.M. , Lui Sing Leung , Lai Kar Neng
Published: August 2002

The mechanism of mesangial IgA deposition is poorly understood in IgA nephropathy (IgAN). Abnormal glycosylation of carbohydrate moieties in the hinge region of the IgA molecule has recently attracted much attention. In this report, we studied galactosylation and sialylation profiles in κ‐ and λ‐IgA1 from patients with IgAN. Total serum IgA1 was isolated from patients with IgAN or healthy controls by jacalin‐affinity chromatography. Six fractions of molecular weight (MW) 50–1,000 kDa were separated by fast protein liquid chromatography (FPLC). Four lectin‐binding assays were used to study the sialylation and the presence of terminal galactose or N‐acetylgalactosamine (GalNAc) in the O‐linked carbohydrate moieties of κ‐ or λ‐IgA1. Maackia amurensis agglutinin (MAA) and Sambucus nigra agglutinin (SNA) lectin recognize α(2,3)‐ and α(2,6)‐linked sialic acid, respectively. Peanut agglutinin (PNA) and Helix aspersa (HA) lectin recognize terminal galactose and GalNAc, respectively. Reduced HA was demonstrated in macromolecular κ or λ‐IgA1 (300–825 kDa) isolated from patients with IgAN (P < 0.05 compared with healthy controls). Lambda‐ but not κ‐IgA1 from patients with IgAN bound less to PNA (P < 0.05). The α(2,3)‐linked sialic acid content in λ‐ but not κ‐IgA1 of MW 150–610 kDa from patients was higher than that of controls (P < 0.005). The α(2,6)‐linked sialic acid content in λ‐IgA1 (300–825 kDa) and κ‐IgA1 (150–610 kDa) from patients was also higher than that of controls. This unusual glycosylation and sialylation pattern of the λ‐IgA1 may have important implications for the pathogenesis of IgAN, as both the masking effect of sialic acid on galactose and the reduced galactosylation will hinder the clearance of macromolecular λ‐IgA1 by asialoglycoprotein receptor of hepatocytes. The negative charge from sialic acid may also favor mesangial deposition of macromolecular λ‐IgA1 in IgAN. J. Clin. Lab. Anal. 16:11–19, 2002. © 2002 Wiley‐Liss, Inc.
The relationship between dissociative tendencies and schizotypy: An artifact of childhood trauma?
Authors: Irwin Harvey J.
Published: August 2002

Previous research has suggested a relationship between dissociative tendencies and schizotypy. This study sought to extend the previous work in two fundamental respects. First, explicit cognizance was taken of the multidimensionality of both dissociative tendencies and schizotypy. Second, the study examined the possibility that the observed correlation between dissociative tendencies and schizotypy is an artifact of the association between each of these personality domains and a history of childhood trauma. Australian adults (N = 116) were administered the Dissociative Experiences Scale, the Schizotypal Personality Questionnaire—Brief, and the Childhood Trauma Questionnaire. Hierarchical regression analysis revealed that both pathological and nonpathological dissociative tendencies were predicted by the dimensions of schizotypy, even after the contribution of childhood trauma had been removed. It is concluded that the relationship between dissociative tendencies and schizotypy is not an artifact of childhood abuse, but the clinical significance of this relationship remains to be established. © 2001 John Wiley & Sons, Inc. J Clin Psychol 57: 331–342, 2001.
Zen meditation and ABC relaxation theory: An exploration of relaxation states, beliefs, dispositions, and motivations
Authors: Gillani Noori B. , Smith Jonathan C.
Published: August 2002

This study is an attempt to rigorously map the psychological effects of Zen meditation among experienced practitioners. Fifty‐nine Zen meditators with at least six years of experience practiced an hour of traditional Zazen seated meditation. A control group of 24 college students spent 60 min silently reading popular magazines. Before relaxation, all participants took the Smith Relaxation States Inventory (SRSI), the Smith Relaxation Dispositions/Motivations Inventory (SRD/MI), and the Smith Relaxation Beliefs Inventory (SRBI). After practice, participants again took the SRSI. Analyses revealed that meditators are less likely to believe in God, more likely to believe in Inner Wisdom, and more likely to display the relaxation dispositions Mental Quiet, Mental Relaxation, and Timeless/Boundless/Infinite. Pre‐ and postsession analyses revealed that meditators showed greater increments in the relaxation states Mental Quiet, Love and Thankfulness, and Prayerfulness, as well as reduced Worry. Results support Smith's ABC Relaxation Theory. © 2001 John Wiley & Sons, Inc. J Clin Psychol 57: 839–846, 2001.
Base rates of WAIS‐R VIQ–PIQ differences in 1593 psychiatric inpatients
Authors: Iverson Grant L. , Woodward Todd S. , Green Paul
Published: August 2002

The purpose of this study was to provide the psychologist with base‐rate tables for the Wechsler Adult Intelligence Scale—Revised (WAIS‐R) Verbal IQ–Performance IQ difference scores in 1593 psychiatric inpatients. Subtables also were provided for each of three primary psychiatric diagnoses (schizophrenia spectrum disorders, bipolar disorders, and depression). The base rates of VIQ–PIQ splits in the full inpatient sample, and those for the subsamples based on primary psychiatric diagnosis, were very similar to those reported in the WAIS‐R standardization sample. Consistent with past research on the standardization sample, the VIQ–PIQ split was correlated positively with Full Scale IQ (FSIQ), indicating that larger splits are more common at the higher IQ levels. Therefore, base‐rate tables also were provided for the total inpatient sample split into five IQ groupings. © 2001 John Wiley & Sons, Inc. J Clin Psychol 57: 1579–1587, 2001.
Activation of apoptosis signal‐regulating kinase 1 by the stress‐induced activating phosphorylation of pre‐formed oligomer
Authors: Tobiume Kei , Saitoh Masao , Ichijo Hidenori
Published: August 2002

Apoptosis signal‐regulating kinase 1 (ASK1) is a MAPKKK family member which activates c‐Jun N‐terminal kinase (JNK) and p38. In non‐stressed cells, ASK1 exists as an inactive complex with the reduced form of thioredoxin. Oxidative stress such as hydrogen peroxide (H2O2) disrupts the ASK1‐thioredoxin complex by oxidization of thioredoxin and thereby activates ASK1. The precise mechanism by which ASK1 is activated after its release from thioredoxin is unknown. Here we show that phosphorylation of Thr845 at the activation loop is essential for ASK1 to be activated by H2O2. ASK1 appears to form a silent homo‐oligomer through its C‐terminal coiled‐coil region in non‐stressed cells. Following H2O2 treatment, pre‐existing ASK1 oligomer undergoes conformational change and creates a new interface within an oligomer, which ultimately leads to trans‐autophosphorylation of Thr845. Thus, direct interaction via the coiled‐coil region is required for self‐scaffolding but not sufficient for activation of ASK1. Importantly, Thr845 of ASK1 can also be trans‐phosphorylated by an unidentified Thr845 kinase in response to H2O2 treatment. We propose that this potential Thr845 kinase may be an ignition kinase that triggers Thr845 phosphorylation in oligomerized and activation‐competent forms of ASK1. J. Cell. Physiol. 191: 95–104, 2002. © 2002 Wiley‐Liss, Inc.