bluuebunny/crossref_metadata_2025 huggingface dataset:
The XAGE family of cancer/testis‐associated genes: Alignment and expression profile in normal tissues, melanoma lesions and Ewing's sarcoma
Authors: Zendman Albert J.W. , van Kraats Annemieke A. , Weidle Ulrich H. , Ruiter Dirk J. , van Muijen Goos N.P.
Published: August 2002

The existence of XAGE genes was first reported after database homology searches for PAGE‐like sequences identified 3 XAGE EST clusters. One of these clusters, XAGE‐1, has in later studies been identified as a cancer/testis‐associated gene. Here, we report the expression profiles of all 3 reported XAGE genes, as well as several splice variants of XAGE‐1, in normal human tissues, Ewing's sarcoma and melanocytic tumors. We also provide the genetic structure of the corresponding genes. Moreover, by searching the databases for XAGE homologues, we identified 3 additional GAGE‐like genes. RT‐PCR studies showed frequent expression in melanoma metastases and Ewing's sarcoma for 2 XAGE‐1‐derived transcripts. XAGE‐2 was expressed at lower frequency in these tissues, while XAGE‐3 was seen only in normal placenta. Due to a frameshift, the largest XAGE‐1 putative protein is far less homologous to GAGE‐like proteins than the other XAGEs. Interestingly, all GAGE‐like genes contain a large secondary open reading frame, coding for putative proteins homologues to the XAGE‐1 primary protein. The XAGE family of cancer/testis‐associated genes is located on chromosome Xp11.21‐Xp11.22. The data outline a superfamily of GAGE‐like cancer/testis antigens, consisting of at least 19 genes. © 2002 Wiley‐Liss, Inc.
Identification and characterization of the murine ortholog (brms1) of breast‐cancer metastasis suppressor 1 (BRMS1)
Authors: Samant Rajeev S. , Debies Michael T. , Shevde Lalita A. , Verderame Michael F. , Welch Danny R.
Published: August 2002

We have cloned a novel metastasis‐suppressor gene (BRMS1) by differential display, comparing metastatic human breast carcinoma cell line MDA‐MB‐435 to its metastasis‐suppressed human chromosome 11 microcell hybrid. Screening of a murine cDNA library led to the identification of a 1.4 kb cDNA with a sequence revealing 85% homology to human BRMS1 within the open reading frame. The predicted protein sequence for the murine ortholog is 95% identical, suggesting that it is strongly conserved across these 2 species. The cloned cDNA was used to screen a murine strain SV129 BAC library to obtain brms1 genomic DNA. Three BAC clones [226(I4), 226(H4) and 239(N7)] were confirmed to encode the entire brms1 gene. Detailed analysis of BAC clone 226(I4) shows that the gene spans 8.5 kb and, like the human gene, is organized into 10 exons and 9 introns. While the exons share a high degree of homology, there are greater differences when comparing intron structures between the human and murine genes. The 5′ upstream region shares about 64% homology with its human counterpart, retaining several of the many putative regulatory elements. Like the human genomic BRMS1, the murine ortholog of the iGnT gene is found upstream of brms1 and the murine ortholog of the RIN1 gene is found downstream of brms1. brms1 was then tested for suppression of metastasis of mouse mammary carcinoma cell line 66cl4 in syngeneic BALB/c mice. Transfection with brms1 did not inhibit 66cl4 primary tumor formation but significantly suppressed its metastatic capability. This suggests that the murine ortholog functions similarly to BRMS1. © 2002 Wiley‐Liss, Inc.
Proteomic alterations of the variants of human aldehyde dehydrogenase isozymes correlate with hepatocellular carcinoma
Authors: Park Kang‐Sik , Cho Sang Yun , Kim Hoguen , Paik Young‐Ki
Published: August 2002

To develop novel markers for hepatocellular carcinomas (HCC), 10 cases were analyzed by 2‐dimensional electrophoresis (2DE) and matrix‐assisted laser desorption ionization mass spectrometry. Results were compared to those of paired adjacent nontumorous liver tissues. Comparative analysis of the respective spot patterns in 2DE revealed that 3 variants of class 3 aldehyde dehydrogenase (ALDH‐3) newly appeared while 2 variants of ALDH‐2 diminished to undetectable levels in HCC. However, 4 ALDH‐1 variants with different pIs remained unaffected. This pattern of concomitant appearance and disappearance of ALDH‐3 and ALDH‐2 variants was consistently observed in all HCC tissues. Our results suggest that alterations of ALDH isozyme variants may be closely correlated to HCC and that proteomic analysis of these proteins might be a novel approach to identify the molecular events in detail during hepatocarcinogenesis. © 2002 Wiley‐Liss, Inc.
Superresolution planar diffraction tomography through evanescent fields
Authors: Lehman Sean K.
Published: August 2002

We consider the problem of noninvasively locating objects buried in a layered medium such as land mines in the ground or objects concealed in a wall. In such environments, the transmitter(s) and receiver(s) are frequently within the near‐field region of the illuminating radiation. In these cases, the scattered evanescent field carries useful information on the scattering object. Conventional diffraction tomography techniques neglect, by their design, the evanescent field. Under near‐field conditions, they treat it as noise as opposed to valid data. If correctly incorporated into a reconstruction algorithm, the evanescent field, which carries high spatial frequency information, can be used to achieve resolution beyond the classical limit of λ/2, or “superresolution.” We build on the generalized holography theory presented by Langenberg to develop a planar diffraction tomography algorithm that incorporates evanescent field information to achieve superresolution. Our theory is based on a generalization of the Fourier transform, which allows for complex spatial frequencies in a manner similar to the Laplace transform. We specialize our model to the case of a two‐dimensional multimonostatic, wideband imaging system, and derive an extended resolution reconstruction procedure. We implement and apply our reconstruction to two data sets collected using the Lawrence Livermore National Laboratory (LLNL) Micropower Impulse Radar (MIR). © 2002 John Wiley & Sons, Inc. Int J Imaging Syst Technol 12, 16–26, 2002
A hybrid approach of wavelet packet and directional decomposition for image compression
Authors: Zhang Chang N. , Wu Xiangyou
Published: August 2002

In this paper, a novel image compression technique, the combination of wavelet packet transform and directional decomposition is proposed. Wavelet packet transform is an increasingly remarkable image compression approach that outperforms the standard wavelet transform in image coding. The directional filtering coding technique, one of the second‐generation image coding techniques, first introduced the concept of directional decomposition. By placing emphasis on edge detection to preserve edge information to exploit the fact that human visual systems are more sensitive to image edge features, a relatively high compression ratio can be obtained. The approach proposed in this paper decomposed an image into a low‐frequency component and a number of highfrequency components, with the edges on each high‐frequency component in its own direction. By a combined process of Cartesian coordinate rotation transform, interpolation, wavelet packet transform, and a coding algorithm, the image can be reconstructed at an improved visual quality at the same bit rate compared with the common wavelet pyramid algorithm. © 2002 Wiley Periodicals, Inc. Int J Imaging Syst Technol 12, 51–55, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ima.10010
Early Head Start: Investigations, insights, and promise
Authors: Robinson JoAnn L. , Fitzgerald Hiram E.
Published: August 2002

The authors review the significance of the research summarized in this special issue, including activities that contribute to successful university–community partnerships. The promise of Early Head Start (EHS) will be realized if investigators focus on moderators and mediators of program effects, program quality, and linkages between Early Head Start and community resources. Key factors that must be taken into account in the analysis of EHS program outcomes include assessing children's transitions to preschool, kindergarten, and elementary school; changes in family personal and social resources; the role of fathers in early child development; and the impact of family bilingualism. ©2002 Michigan Association for Infant Mental Health.
A dynamic multinomial probit model for brand choice with different long‐run and short‐run effects of marketing‐mix variables
Authors: Paap Richard , Franses Philip Hans
Published: August 2002

In this paper we propose a dynamic multinomial probit model in order to estimate the long‐run and short‐ run effects of marketing mix variables on brand choice. The latent variables, which contain the unobserved perceived utilities, follow a first‐order vector error correction autoregressive process of order 1 with current and lagged explanatory variables. The unrestricted autoregressive parameter matrix concerns the intertemporal correlation in perceived utilities of households over purchase occasions and indicates the persistence in brand choice. As explanatory variables we consider relative prices and promotional activities like feature and display. An important and novel feature of our model is that it allows for different long‐run and short‐run effects of promotional activities, thereby extending the models that are currently available in the literature. Additionally, to account for different base preferences for brands across households, we allow for consumer heterogeneity. Our application concerns a panel of households choosing among several brands of a FMCG. Our estimated model turns out to be an improvement over a static model and over a model with only short‐run effects, in terms of in‐sample fit and out‐of‐sample forecasts. Copyright © 2000 John Wiley & Sons, Ltd.
Ozone induces impairment of adrenergic relaxation in thoracic guinea pig tracheas
Authors: Sommer Bettina , Vargas Mario H. , Campos María G. , Montaño Luis M.
Published: August 2002

The effect of ozone on airway relaxation mechanisms has been seldom studied. We exposed guinea pigs to ozone (0.3, 0.6 or 1.2 ppm for 4 h) and studied the in vitro tracheal responses to isoproterenol and nitroprusside, looking for differences between cervical and thoracic regions. We found that ozone did not alter responses to nitroprusside, whereas it produced a concentration‐dependent decrease in the responses to isoproterenol in thoracic but not cervical tracheas. Thus, in isolated organ studies care should be taken to avoid mixing cervical and thoracic tracheal regions, at least when adrenergic responses are to be evaluated. Copyright © 2001 John Wiley & Sons, Ltd.
Contribution to the penetration of radionuclides across the skin. Concentration dependence of strontium through the skin in vitro
Authors: Bauerová Katarína , Kassai Zoltán , Koprda Vasil , Harangozó Margita
Published: August 2002

Toxicological studies of radionuclide passage across the skin, which represents a crucial barrier of radiation, are important for ensuring the quality of the environment. Both 137Cs and 90Sr are most frequently involved in radionuclide contamination of the human body. In our study, we selected 90Sr because this radionuclide is chemically very close to the bio‐element calcium. The permeation of 90Sr from donor solution across the intact skin of 5‐ or 9‐day‐old rats (5DR, 9DR) and across stripped and splitted skin of the 5DR was studied. The experiments in vitro were carried out using vertical diffusion cells. Strontium chloride (SrCl2) was used as carrier in the donor solution in different concentrations. Liquid scintillation spectrometry was applied for radiation detection.

The experiments showed that: the permeated fraction of 90Sr2+ was indirectly proportional to the carrier concentration in the donor solution; the stratum corneum was found to be the principal penetration barrier of strontium; and in the case of the 9DR the dominant route of strontium penetration was along the follicles. Copyright © 2001 John Wiley & Sons, Ltd.
Toxicity of trichloroethylene following inhalation and drinking contaminated water
Authors: Waseem Mohammad , Ali Mohamad , Dogra Shashi , Dutta Kalyan Kumar , Kaw Jawahir Lal
Published: August 2002

The neurobehavioural effects of trichloroethylene (TCE) were studied in rats following administration of the solvent orally (350, 700 and 1400 ppm in drinking water for 90 days) and through inhalation (376 ppm for 4 h a day, 5 days per week for 180 days). Various aspects of spontaneous locomotor activity were assessed at different periods after exposure through either of the routes. Oral exposure to TCE had no significant effect on spontaneous locomotor activity or cognitive ability, whereas inhalation to the solvent resulted in an increase in the distance travelled and horizontal activity counts at day 30 but a decrease at day 60 of exposure. The time spent in ambulatory and stereotypic movements as well as the number of stereotypic movements were enhanced significantly only at day 30. The resting time was decreased at day 30 but enhanced at day 60 of exposure. The learning ability was not affected significantly up to day 180. The results highlight the neurotoxic potential of inhalation exposure to TCE. Copyright © 2001 John Wiley & Sons, Ltd.
Detection of oxidative species and low‐molecular‐weight DNA in skin following dermal exposure with JP‐8 jet fuel
Authors: Rogers James V. , Gunasekar Palur G. , Garrett Carol M. , Kabbur Mahendra B. , McDougal James N.
Published: August 2002

Dermal absorption of JP‐8 jet fuel can lead to skin irritation within hours after exposure. This study detected the formation of oxidative species and low‐molecular‐weight DNA in rat skin as potential indicators of JP‐8‐induced skin injury. At 0, 1, 2, 4 and 6 h after the beginning of a 1‐h exposure, skin samples were removed and analyzed for oxidative species formation and low‐molecular‐weight DNA analysis. At 1, 2 and 4 h, mean oxidative species levels increased significantly (P < 0.05) above unexposed samples. Significantly higher (P < 0.05) low‐molecular‐weight DNA values were observed at 4 and 6 h compared with unexposed controls. These results demonstrate significant increases in oxidative species and low‐molecular‐weight DNA levels in the skin following dermal exposure to JP‐8. These responses may serve as indicators of skin injury following exposure to JP‐8 jet fuel and other volatile chemicals or mixtures. Copyright © 2001 John Wiley & Sons, Ltd.
Influence of water extracts from the surface of two Yew (Taxus) species on mites (Tetranychus urticae)
Authors: Furmanowa Miroslawa , Kropczyńska Danuta , Zobel Alicja , Glowniak Kazimierz , Oledzka Hanna , Józefowicz Joanna , Sahajdak Agnieszka , Józetczyk Aleksandra
Published: August 2002

Taxus cuspidata and Taxus media var. Hicksii contain paclitaxel, among other taxoids, on the surface of the needles. These compounds were removed by 5‐s dipping of the needles in water just below its boiling point at 96°C and at 60°C and 40°C. Taxus cuspidata contained a fourfold higher concentration of paclitaxel than Taxus media var. Hicksii. The extract with the higher concentration of paclitaxel was more harmful to the mites Tetranychus urticae Koch, increasing their mortality 150%, prolonging development by ca. 20% and lowering the average fecundity from 112 in the control to 16.13 after treatment with Taxus cuspidata; also, the net reproductive rate dropped from 70.24 to 6.70, which is more than a tenfold reduction. Copyright © 2002 John Wiley & Sons, Ltd.
Effect of cyclosporin A in Lewis rats in vivo and HeLa cells in vitro
Authors: Sovcikova Andrea , Tulinska Jana , Kubova Jana , Liskova Aurelia , Syrova Dagmar , Horakova Katarina
Published: August 2002

The aim of this study was to compare the effect of cyclosporin A (CsA) in inbred Lewis rats with published assessment of immunotoxicity in ‘classical’ outbred Wistar rats. A second purpose was to consider the contribution of a panel of in vitro assays in cell cultures when added to an immunotoxicity study in vivo.

The in vivo effect of CsA was investigated in a 28‐day subacute immunotoxicity study in male Lewis rats at three different concentrations: 1.25, 5 and 20 mg kg−1. The highest dose of CsA exceeded the maximum tolerated dose. A drop in body, spleen and popliteal lymph node weight of exposed animals displayed symptoms of toxicity. At a high toxic dose, haematological changes showed a decrease in the leucocyte count and in the percentage of lymphocytes, and an increase in the percentage of polymorphonuclear leucocytes. The haematocrit was significantly dose‐dependently suppressed in all rats exposed to CsA. A similar dose‐dependent depression of the mean cell volume of erythrocytes was found in rats given high and middle doses of CsA. The phagocytic activity of polymorphonuclear leucocytes and monocytes also was significantly dose‐dependently suppressed. No significant changes in primary antibody response to sheep erythrocytes or in vitro proliferative response of spleen lymphocytes to mitogens were found in those rats.

A battery of in vitro cytotoxicity methods was selected for the evaluation of metabolic and functional activity of subcellular organelles (mitochondria, lysosomes) and for the detection of drug‐induced superoxide‐mediated damage in HeLa cells. This cell line was chosen because it has a lower activity of superoxide dismutase (SOD) than normal cells and is sufficiently sensitive for the detection of the induction of oxygen radicals. The in vitro results indicated a direct relationship between CsA cytotoxicity and a change in the mitochondrial enzyme activity, as well as an induction of superoxide production.

The results of the study indicated that a combination of selected in vivo and in vitro methods is an inexpensive way to obtain more complex information on cell status affected by xenobiotics. Copyright © 2002 John Wiley & Sons, Ltd.
In vitro characterization and in vivo properties of a carbonated apatite bone cement
Authors: Khairoun I. , Magne D. , Gauthier O. , Bouler J. M. , Aguado E. , Daculsi G. , Weiss P.
Published: August 2002

This study evaluated the in vivo behavior of an injectable calcium phosphate bone cement implanted in bone defects at the distal end of rabbit femora. After 3 weeks, samples were harvested and processed for undecalcified sectioning. Scanning electron microscopy, transmission electron microscopy, and Fourier transform infrared microspectroscopy showed direct contact of bone and cement without soft tissue interposition, biocompatibility, and bioactivity with osteoconductive properties. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 60: 633–642, 2002
Effect of porosity reduction by compaction on compressive strength and microstructure of calcium phosphate cement
Authors: Barralet J.E. , Gaunt T. , Wright A. J. , Gibson I. R. , Knowles J. C.
Published: August 2002

Hydroxyapatite (HA) calcium phosphate cements (CPCs) are attractive materials for orthopedic applications because they can be molded into shape during implantation. However their low strength and brittle nature limits their potential applications to principally non‐load‐bearing applications. Little if any use has been made of the HA cement systems as manufacturing routes for preset HA bone grafts, which although not moldable pastes, are resorbable, unlike HA sintered ceramic. It is known that the strength of cements can be increased beyond that attainable from slurry systems by compaction, and this study investigates whether compaction significantly alters the specific surface area and pore‐size distribution of CPC prepared according to the method of Brown and Chow. Compaction pressures of between 18 and 106 MPa were used to decrease the porosity from 50 to 31%, which resulted in an increase in the wet compressive strength from 4 to 37 MPa. The Weibull modulus was found to increase as porosity decreased; in addition the amount of porosity larger than the reactant particle size increased as porosity decreased. It is proposed that this was caused by a combination of voids created by the aqueous solvent used in fabrication and shrinkage that occurs on reaction. The specific surface area was unchanged by compaction. © 2001 Wiley Periodicals, Inc. J Biomed Mater Res (Appl Biomater) 63: 1–9, 2002
Use of real‐time gene‐specific polymerase chain reaction to measure RNA expression of three family members of rat cytochrome P450 4A
Authors: Bleicher Kimberly B. , Pippert Todd R. , Glaab Warren E. , Skopek Thomas R. , Sina Joseph F. , Umbenhauer Diane R.
Published: August 2002

Exposure of rats to peroxisome proliferators induces members of the cytochrome P450 4A (CYP4A) family. In rats, the CYP4A family consists of four related genes, CYP4A1, CYP4A2, CYP4A3, and CYP4A8. We are specifically interested in examining CYP4A1, CYP4A2, and CYP4A3, each of which is expressed in a tissue‐dependent and sex‐dependent manner. While CYP4A1 is sufficiently different from the other two members to enable relatively easy specific quantitation, the close similarity between CYP4A2 and CYP4A3 makes quantitative discrimination difficult. We have combined a fluorescent real‐time PCR assay (TaqMan®) with the sequence‐specific mismatch amplification mutation assay (MAMA) to allow us to carry out specific quantitation of all three members of this family. The assay is designed such that a single fluorescent TaqMan® probe binds to all three gene products, while specificity is conferred by sequence‐specific primers. This specific MAMA technique takes advantage of the ability of Taq polymerase to distinguish between the two cDNAs based on mismatches at the 3′ end of a PCR primer. In the 84‐base PCR product used for this assay, there is only a single‐base difference between CYP4A2 and CYP4A3. Despite this similarity, there is at least a 1000‐fold discrimination between the two sequences, using CYP4A2 or CYP4A3 specific standards. Analysis of rat liver RNA from both sexes demonstrates that this discrimination is also achieved in complex RNA mixtures. This technique should be broadly applicable to other areas of research such as allelic discrimination, detecting mutational hotspots in tumors, and discrimination among closely related members of other gene families. © 2001 John Wiley & Sons, Inc. J Biochem Mol Toxicol 15:133–142, 2001
Extensive protein carbonylation precedes acrolein‐mediated cell death in mouse hepatocytes
Authors: Burcham Philip C. , Fontaine Frank
Published: August 2002

Allyl alcohol hepatotoxicity is mediated by an alcohol dehydrogenase‐derived biotranformation product, acrolein. This highly reactive α,β–unsaturated aldehyde readily alkylates model proteins in vitro, forming, among other products, Michael addition adducts that possess a free carbonyl group. Whether such damage accompanies acrolein‐mediated toxicity in cells is unknown. In this work we established that allyl alcohol toxicity in mouse hepatocytes involves extensive carbonylation of a wide range of proteins, and that the severity of such damage to a subset of 18–50 kDa proteins closely correlated with the degree of cell death. In addition to abolishing cytotoxicity and glutathione depletion, the alcohol dehydrogenase inhibitor 4‐methyl pyrazole strongly attenuated protein carbonylation. Conversely, cyanamide, an aldehyde dehydrogenase inhibitor, enhanced cytotoxicity and protein carbonylation. Since protein carbonylation clearly preceded the loss of membrane integrity, it may be associated with the toxic process leading to cell death. © 2001 John Wiley & Sons, Inc. J Biochem Mol Toxicol 15:309–316, 2001
Localization of estradiol‐responsive region in the phenobarbital‐responsive enhancer module of mouse Cyp2b‐10 gene
Authors: Yamamoto Makoto , Sakuma Tsutomu , Ichimaru Hajime , Nemoto Nobuo
Published: August 2002

The mouse Cyp2b‐10 gene is inducible by treatment with estradiol as well as so‐called phenobarbital (PB)‐like inducers. To identify 5′‐flanking elements responsible for induction by estradiol, we carried out reporter gene assays using a primary mouse hepatocyte culture system. Cyp2b‐10 gene‐driven luciferase activities were induced by estradiol as well as PB in this system. Deletion analysis demonstrated that the sequence contained within the region from −2331 bp to −2281 bp was responsible for the estradiol‐induced luciferase activity. This region corresponds to the core element of PB‐responsive enhancer module (PBREM). Several nucleotide mutations in the putative binding sites of the PBREM core element showed that the NR1 site was required for estradiol induction, and the same element was required for PB induction. These results indicate that estradiol induces Cyp2b‐10 gene expression via PBREM. © 2001 John Wiley & Sons, Inc. J Biochem Mol Toxicol 15:76–82, 2001
Erythrocytapheresis for Plasmodium falciparum infection complicated by cerebral malaria and hyperparasitemia
Authors: Zhang Y. , Telleria L. , Vinetz J.M. , Yawn D. , Rossmann S. , Indrikovs A.J.
Published: August 2002

In malaria due to Plasmodium falciparum, life‐threatening complications are in part related to the degree of parasitemia. Whole blood exchange and red blood cell exchange (RCE) have been used for the rapid removal of parasites from the circulation of patients with a high parasite load complicated by cerebral, pulmonary, and renal dysfunction. We have treated three 5–45‐year‐old patients with hyperparasitemia and end‐organ dysfunction with red cell exchange by automated apheresis as an adjunct to specific anti‐malarial chemotherapy. Parasitemia dropped more than 80% in all three patients immediately after the exchange, and all patients had an uneventful and full recovery. In combination with effective anti‐malarial chemotherapy, apheresis RCE is a safe and rapid approach to treat complicated malaria due to P. falciparum. J. Clin. Apheresis. 16:15‐18, 2001. © 2001 Wiley‐Liss, Inc.
Lepromatous vasculitis successfully treated by plasma exchange (PE)
Authors: Ruzzenenti M.R. , Bruni R. , Florio G. , De Luigi M.C. , Lercari G. , Barabino G.F. , Nunzi E. , Valbonesi M.
Published: August 2002

Vascular involvement is presently considered a "common pathway" in a number of diseases that is mediated by circulating immune complexes (CIC). CIC are found in the circulation when the disease is active and in single patients their level may parallel disease activity. Lepromatous leprosis is characterized by the presence of CIC and deposits of immunoglobulins and complement in vascular lesions of the different organs and an Arthus‐like mechanism is considered as the basis for the clinical picture. The same mechanism is considered to play an essential pathophysiologic role in Lucio's phenomenon, which is characterized by lymphohistiocytic vascular infiltrates with or without thrombosis and secondary cutaneous infarction. Lepromatous vascular involvement is mediated by CIC whose antigen composition is known, the same as it is with HCV mediated cryoglobulinemia, HBV positive panarteritis nodosa, rheumatoid vasculitis, or Wagner's granulomatosis, which are usually treated by PE [1‐3]. PE has been employed for lepromatous vasculitis since 1979 [4] and other cases have been successfully treated afterwards [5,6]. We report on another patient successfully treated by plasma exchange.
Platelet transfusion therapy
Authors: Goodnough Lawrence Tim
Published: August 2002

The relative merits of apheresis platelets and platelet concentrates are undergoing debate due to evolving issues of safety, inventory, and cost. The application of photochemical inactivation technology may eliminate any rationale for the use of apheresis platelets rather than pooled platelet concentrates, so that the relative merits of these two alternatives will be debated over costs and inventory. Doses of apheresis platelets are determined by donor platelet count and by platelet yield. The generation of a platelet apheresis inventory has been accompanied by a decline in whole blood inventory; research into the impact of these distinct donor pools on national blood policy is needed. J. Clin. Apheresis. 16:43‐48, 2001. © 2001 Wiley‐Liss, Inc.
How to Control Soaring Costs of Health Care
Authors: Goldberg Stephen R. , Danko Dori
Published: August 2002

Managed care is no longer a silver bullet to cure growing corporate health care costs. But innovative new
trends in health care benefits can help, say the authors. And they also offer some practical strategies for
managing health care costs. © 2002 Wiley Periodicals, Inc.
Sharpening Focus: How One Company Built a Strategic Measurement System
Authors: Focht Scott
Published: August 2002

A formalized strategic management program at First of Omaha Merchant Processing has helped align the
organization through development of strategic objectives and corresponding action plans. As a result, the
company's budget process now works in tandem with its planning cycle, and its organizational structure now
supports implementation of strategy. © 2002 Wiley Periodicals, Inc.
Will Technology Defeat Your Auditor?
Authors: Munter Paul
Published: August 2002

Enron is only the latest of a growing list of frauds that went undetected for years. Even if your auditor is
honest, the widespread use of technology makes it tougher for him to find the crime—and make the bad guys do
the time. But what do you have a right to expect from your auditor? © 2002 Wiley Periodicals,
Inc.
Helping ensure successful implementations of activity‐based management
Authors: Nair Mohan
Published: August 2002

This article explains the many change management and organizational considerations involved in implementing
activity‐based management. Avoiding the many possible pitfalls—which have been widely identified and
discussed elsewhere—will get users far. But there are also many factors that can help companies as they plan
and implement activity‐based costing (ABC) and activity‐based cost management
(ABC/M). © 2002 John Wiley & Sons, Inc.
Insulin‐like growth factor‐1 protects peroxynitrite‐induced cell death by preventing cytochromec‐induced caspase‐3 activation
Authors: Saeki Makio , Maeda Sadaaki , Wada Kouichirou , Kamisaki Yoshinori
Published: August 2002

We investigated the effect of IGF‐1 on cell death induced by peroxynitrite in human neuroblastoma SH‐SY5Y cells. Exposure of the cells to 3‐morpholinosydnonimine (SIN‐1), a peroxynitrite donor, caused cytochromecrelease from the mitochondria, caspase‐3‐like activation, and cell death. Pre‐incubation of the cells with the caspase‐3 inhibitor partially prevented SIN‐1‐induced cell death. Simultaneous addition of IGF‐1 reduced SIN‐1‐induced caspase‐3‐like activation and cell death, whereas IGF‐1 failed to reduce the release of cytochromec. IGF‐1 increased Akt phosphorylation, and Akt phosphorylation was inhibited by wortmannin, an inhibitor of phosphatidylinositol 3‐kinase. In addition, wortmannin prevented IGF‐1‐evoked inhibition of cell death and caspase‐3‐like activation. In a cell‐free system, addition of cytochromecto cytosolic fraction resulted in caspase‐3‐like activation. The activation was reduced when the cytosolic fraction prepared from IGF‐1‐treated cells was used. These results suggest that IGF‐1 protects peroxynitrite‐induced cell death downstream of cytochromecrelease through the inhibition of caspase‐3‐like activation. J. Cell. Biochem. 84: 708–716, 2002. © 2002 Wiley‐Liss, Inc.
Membrane‐bound and cytosolic forms of heterotrimeric G proteins in young and adult rat myocardium: Influence of neonatal hypo‐ and hyperthyroidism
Authors: Novotny Jiri , Bouřová Lenka , Kolář František , Svoboda Petr
Published: August 2002

Membrane and cytosolic fractions prepared from ventricular myocardium of young (21‐day‐old) hypo‐ or hyperthyroid rats and adult (84‐day‐old) previously hypo‐ or hyperthyroid rats were analyzed by immunoblotting with specific anti‐G‐protein antibodies for the relative content of Gsα, Giα/Goα, Gqα/G11α, and Gβ. All tested G protein subunits were present not only in myocardial membranes but were at least partially distributed in the cytosol, except for Goα2, and G11α. Cytosolic forms of the individual G proteins represented about 5–60% of total cellular amounts of these proteins. The long (Gsα‐L) isoform of Gsα prevailed over the short (Gsα‐S) isoform in both crude myocardial membranes and cytosol. The Gsα‐L/Gsα‐S ratio in membranes as well as in cytosol increased during maturation due to a substantial increase in Gsα‐L. Interestingly, whereas the amount of membrane‐bound Giα/Goα and Gqα/G11α proteins tend to lower during postnatal development, cytosolic forms of these G proteins mostly rise. Neonatal hypothyroidism reduced the amount of myocardial Gsα and increased that of Giα/Goα proteins. By contrast, neonatal hyperthyroidism increased expression of Gsα and decreased that of Giα and G11α in young myocardium. Changes in G protein content induced by neonatal hypo‐ and hyperthyroidism in young rat myocardium were restored in adulthood. Alterations in the membrane‐cytosol balance of G protein subunits associated with maturation or induced by altered thyroid status indicate physiological importance of cytosolic forms of these proteins in the rat myocardium. J. Cell. Biochem. 82: 215–224, 2001. © 2001 Wiley‐Liss, Inc.
Impact of cell swelling on proliferative signal transduction in the liver
Authors: Kim Robin D. , Stein Gary S. , Chari Ravi S.
Published: August 2002

Cellular swelling has emerged as an important initiator of metabolic and proliferative changes in various cells. Because of the unique regenerative capacity of the adult liver, researchers have delineated key intracellular signals that are activated following mitogens, injury, and partial hepatectomy. Although hepatocellular swelling is commonly observed following these regenerative stimuli, only recently has the relationship between cell volume increase and proliferative activity been investigated; to date, the data implicating cell volume increase with hepatocyte regeneration has been mostly indirect. Hepatocyte swelling has been demonstrated in various clinical scenarios from sepsis, hepatic resection, ischemia‐reperfusion injury, glucocorticoid excess, and hyperinsulinemia. Using various in vivo and in vitro models of hepatocyte swelling, particularly hypo‐osmotic stress, investigators have demonstrated changes in cellular structure: (1) cell membrane stretch, (2) cytoskeletal microtubule and microfilament reorganization, and (3) alterations in cytoskeletal‐membrane complexes. Similar studies have demonstrated a causal relationship between cell volume increase and intracellular signals: (1) activation of cytoplasmic signaling cascades such as MAPKs, PI‐3‐K, and PKC, (2) activation of proliferative transcription factors NF‐κB, AP‐1, STATs, C/EBPs, and (3) transcription of metabolic and immediate early genes of regeneration. Through mechanotransduction, or the translation of physical changes to chemical signals, cell volume is a potent effector of these signaling events. Growing evidence demonstrates a link between these physical and chemical changes in the swelling‐mediated growth in the liver. ©2001 Wiley‐Liss, Inc.
G protein β2 subunit antisense oligonucleotides inhibit cell proliferation and disorganize microtubule and mitotic spindle organization
Authors: Wu Han‐Chung , Huang Pie‐Hsien , Chiu Chien‐Yu , Lin Chin‐Tarng
Published: August 2002

The association of G protein β2 subunit (Gβ2) with mitotic spindles in various mammalian cells has been demonstrated previously. Recently, we have identified the association of Gβ2 protein with microtubules (Wu et al., [1998] J. Cell. Biochem. 70: 552‐562). In the present experiment we have demonstrated the possible functional role of Gβ2 in microtubule and mitotic spindle organization in mammalian cells. When Gβ2 antisense phosphorothioate oligonucleotides were transfected into mammalian cells, inhibition of cell proliferation with cell death after a 4‐day treatment was observed. If the transfected cells were incubated for two days and their Gβ2 and microtubules were examined by Western blotting and immunofluorescence localization, marked reduction of the Gβ2 protein, fragmentation and disassembly of cytoplasmic microtubules, and disorganized mitotic spindles were found. We conclude that the Gβ2 protein is closely associated with microtubule assembly and may play a potential role in the regulation of cell proliferation and microtubule and mitotic spindle organization in mammalian cells. J. Cell. Biochem. 83: 136–146, 2001. © 2001 Wiley‐Liss, Inc.
Characterization of the biologically important interaction between troponin C and the N‐terminal region of troponin I
Authors: Ngai Sai‐Ming , Hodges Robert S.
Published: August 2002

The N‐terminal regulatory region of Troponin I, residues 1–40 (TnI 1–40, regulatory peptide) has been shown to have a biologically important function in the interactions of troponin I and troponin C. Truncated analogs corresponding to shorter versions of the N‐terminal region (1–30, 1–28, 1–26) were synthesized by solid‐phase methodology. Our results indicate that residues 1–30 of TnI comprises the minimum sequence to retain full biological activity as measured in the acto‐S1‐TM ATPase assay. Binding of the TnI N‐terminal regulatory peptides (TnI 1–30 and the N‐terminal regulatory peptide (residues 1–40) labeled with the photoprobe benzoylbenzoyl group, BBRp) were studied by gel electrophoresis and photochemical cross‐linking experiments under various conditions. Fluorescence titrations of TnI 1–30 were carried out with TnC mutants that carry a single tryptophan fluorescence probe in either the N‐ or C‐domain (F105W, F105W/C domain (88–162), F29W and F29W/N domain (1–90)) (Fig. 1). Low Kd values (Kd < 10−7 M) were obtained for the interaction of F105W and F105W/C domain (88–162) with TnI 1–30. However, there was no observable change in fluorescence when the fluorescence probe was located at the N‐domain of the TnC mutant (F29W and F29W/N domain (1–90)). These results show that the regulatory peptide binds strongly to the C‐terminal domain of TnC. © 2001 Wiley‐Liss, Inc.
Comparative analysis of the uptake and expression of plasmid vectors in human ciliary and retinal pigment epithelial cells in vitro
Authors: Chaum Edward
Published: August 2002

The retinal pigment epithelium is uniquely suited to gene therapy that uses lipid‐mediated DNA transfer due to its high phagocytic activity in situ. We compared the relative efficacy of phagocytosis on the uptake of labeled plasmid vectors by retinal pigment epithelial and ciliary epithelial cells in vitro. Relative levels of endocytosis were then compared with the efficiency of marker transgene expression in these cells. Human retinal pigment epithelial and ciliary epithelial cells from a single donor were isolated and expanded in vitro. Polyplex‐mediated transfections were performed using a rhodamine‐labeled expression vector for green fluorescent protein. Rhodamine‐labeled endosomes were examined by fluorescence microscopy at different time points. Rhodamine labeling and green fluorescent protein expression were analyzed by flow cytometry 48 h after transfection. These gene transfer studies showed that expression of transgenes does occur in both human retinal pigment epithelial and ciliary epithelial cells in vitro. Endocytosis of labeled plasmid vectors occurs at a significantly higher number and density in retinal pigment epithelial cells than in ciliary epithelial cells (P < 0.04). However, the efficiency of marker transgene expression is similar in the two cell types. These studies demonstrate that the higher intrinsic phagocytic activity does not enhance the efficacy of transgene expression in retinal pigment epithelial cells in vitro. Both human retinal pigment epithelial and ciliary epithelial cells are competent recipients for lipid‐mediated gene transfer, and transgene expression occurs at similar levels in both cell types. J. Cell. Biochem. 83: 671–677, 2001. © 2001 Wiley‐Liss, Inc.
Pure component spectral reconstruction from mixture data using SVD, global entropy minimization, and simulated annealing. Numerical investigations of admissible objective functions using a synthetic 7‐species data set
Authors: Widjaja Effendi , Garland Marc
Published: August 2002

A combination of singular value decomposition, entropy minimization, and simulated annealing was applied to a synthetic 7‐species spectroscopic data set with added white noise. The pure spectra were highly overlapping. Global minima for selected objective functions were obtained for the transformation of the first seven right singular vectors. Simple Shannon type entropy functions were used in the objective functions and realistic physical constraints were imposed in the penalties. It was found that good first approximations for the pure component spectra could be obtained without the use of any a priori information. The present method out performed the two widely used routines, namely Simplisma and OPA‐ALS, as well as IPCA. These results indicate that a combination of SVD, entropy minimization, and simulated annealing is a potentially powerful tool for spectral reconstructions from large real experimental systems. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 911–919, 2002
Strain induced bond localization in strained aromatic compounds with extended π systems
Authors: Stanger Amnon , Tkachenko Elena
Published: August 2002

The influence of small rings annulated to aromatic rings is usually additive. However, in some systems the behavior is nonadditive, for example, in tricarbonyliron‐cyclobutadienobenzene versus tris(tricarbonylironcyclobutadieno)benzene. A study of dimethylenecyclobutabenzene, 1,3‐bis(dimethylenecyclobuta)benzene, tris(dimethylenecyclobuta)benzene, and their bora, imino, and oxo derivatives is presented. The behavior of these systems ranges from an almost perfect additivity (in the bora derivatives) to nonadditive behavior (in the oxo derivatives) where the single ring annulated system shows a negative difference between the bonds endocyclic and exocyclic to the annulated small ring (negative ΔR; anti‐Mills–Nixon distortion), the doubly annulated system shows ΔR=0, and the triply annulated system shows positive ΔR (Mills–Nixon distortion). The geometrical properties of the systems are analyzed in terms of the strain, bond curvature, and electronegativity of the exocyclic substituent. These atomic and σ properties are found to be responsible for the structural properties whereas π factors are of minor or no importance. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1377–1386, 2001
Quantitative characterization of the PC bonds in ylides of phosphorus
Authors: Mitrasinovic Petar M.
Published: August 2002

The nature of the carbon–phosphorus bond in trivalent and pentavalent carbon phosphorus compounds is currently a matter of some dispute. These compounds contain unusual bonds, unusual in the sense that the behavior of electrons in the compounds does not conform to that expected solely on the basis of carbon–carbon and carbon–hydrogen bonds. Quantitative measures of how a single electron, as a wave, is shared between any two spatial points are given by means of the sharing amplitude and the sharing index.1 These quantities are orbital independent, rooted in the single particle density matrix, and do not depend on arbitrary localization procedures. The quantitative characterization of the PC bonds in molecules such as PHCH2, PH3CH2, PF3CH2, and PH3CHF was carried out by means of the sharing indices. On the basis of interbasin sharing indices, the PC bonds are: (mostly) double in PHCH2, and single in PH3CH2, PF3CH2, and PH3CHF. On the basis of the group basin charges and intergroup sharing indices between the CH2 (or CHF) groups and the PH1,3 (or PF3) groups, the molecules are ionic with double bonds between the groups (in line with an ylene form). The sharing indices between atoms, which are not directly linked (secondary sharing indices), indicate that the electrons are quite delocalized over the basins of the following groups: CPH in PHCH2, CPH3 in PH3CH2, CPF3 in PF3CH2, and CPH3 in PH3CHF. The sharing indices and the sharing amplitude offer the needed tools to put our understanding of the chemistry of a large number of compounds on a rigorous basis by elucidating the behavior of a single electron in a many electron system. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1387–1395, 2001
Molecular mechanics calculations on carbonyl compounds. II. Open‐chain ketones
Authors: Langley Charles H. , Lii Jenn‐Huei , Allinger Norman L.
Published: August 2002

Open‐chain aliphatic ketones were studied with the molecular mechanics (MM4) force field. A total of seven compounds were examined. Structures were well fit, including moments of inertia. Rotational barriers, vibrational spectra, and dipole moments were also well fit. The overall root mean square errors for MM3 and MM4 were 0.27 and 0.18%, respectively, for the six moments of inertia (known experimentally for two compounds) and 31 and 20 cm−1, respectively, for the vibrational frequencies (over 99 weighted modes). © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1426–1450, 2001
Global physicochemical properties as activity discriminants for the mGluR1 subtype of metabotropic glutamate receptors
Authors: Filizola Marta , Tasso Silvina M. , Loew Gilda H. , Villar Hugo O.
Published: August 2002

Metabotropic glutamate receptors (mGluRs) are important as candidate therapeutic targets for many neurological disorders. In the present work, the focus has been on the mGluR1 subtype, where agonists have a proconvulsant profile while antagonists exert anticonvulsant activity. Identification of molecular determinants for the inhibition of mGluR1 provides a new avenue for the discovery and development of novel anticonvulsant drugs. Spatial configuration of key groups alone cannot explain activation selectivity at this specific receptor subtype. In fact, all known agonists and antagonists acting at mGluR1 can accommodate the same critical moieties in a similar geometric arrangement that corresponds to the extended conformation of glutamate. Therefore, other factors must account for the differences in activation. This study presents the results of an analysis of a large suite of steric, topological, electrostatic, and thermodynamic molecular properties calculated for a representative set of potent mGluR1 agonists and antagonists. Global steric parameters and the total nonpolar area provide discrimination between the mGluR1 agonists and antagonists considered in the present work. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 2018–2027, 2001
Rb+/Cs+ selectivity of benzo and tribenzo derivatives of the 21C7 crown ether. A density functional study
Authors: Golebiowski Jérôme , Lamare Véronique , Ruiz–López Manuel F.
Published: August 2002

A density functional study has been performed on Rb+ and Cs+ complexes of mono and tribenzo derivatives of the 21Crown7 crown ether. Calculations have been carried out using the B3LYP functional together with a split valence basis set with additional polarization and diffuse functions. The cations have been described with effective core potentials. Structures of the tribenzo‐21Crown7 are compared to X‐ray data. The Rb+/Cs+ affinity of the benzo and tribenzo derivatives in gas phase is discussed on the basis of binding energies, strain energies, and electrostatic contributions. For the first time, a detailed description of the effect arising from the presence of benzo groups is described. On one hand, the benzo groups decrease the electronic density on the ether oxygen atoms. On the other hand, they confer a stronger electronic polarizability to the ligand. The energetic analysis shows that the polarization contributions play a crucial role and reach up to 29% of the total electrostatic energy. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 724–731, 2002