bluuebunny/crossref_metadata_2025 huggingface dataset:
Treasury strategies for tough times
Authors: Jasmon Abadan
Published: October 2003

When there's an economic slump, you need different treasury management strategies. To stay liquid,
competitive, and profitable, you must review your practices in three important areas: cash, credit, and
inventory
management. The author discusses new strategies you can use and looks at what the most innovative companies are
doing. © 2003 Wiley Periodicals, Inc.
The euro: How will it impact your treasury operations?
Authors: Goldberg Stephen R. , Danko Dori , Stovall Dennis
Published: October 2003

Brace for impact, warn the authors. The effect of euro currency conversion will be
far‐reaching—and will significantly affect U.S. companies' operations. The authors explain
why and offer strategies that will help you avoid problems. © 2003 Wiley Periodicals,
Inc.
Underfunded pension plans: Is more debt the answer?
Authors: Smith Ola , Langsam Sheldon , Kreuze Jerry
Published: October 2003

Underfunded pension plans are a big problem. S&P 500 companies alone have a whopping pension deficit of
$239 billion. Now one company, General Motors, is issuing debt to cover the gap. But should other
companies do the same thing? Should you? © 2003 Wiley Periodicals, Inc.
Corporate philanthropy: When is giving effective?
Authors: Raiborn Cecily , Green Antoinette , Todorova Lyudmila , Trapani Toni , Watson Wilborne E.
Published: October 2003

We've all heard the saying, “Give and ye shall receive.” But for corporations, that's
only true if you're very choosy about who receives your charitable donations. With so many candidates, how
can you select beneficiaries to generate the greatest rewards—for your company, your employees, and
society? © 2003 Wiley Periodicals, Inc.
U.S. vs. Canada: Are we really tougher on fraud?
Authors: Reinstein Alan , Green Brian Patrick
Published: October 2003

What are the differences between U.S. and Canadian auditing for fraud? Many U.S. financial executives
have some familiarity with U.S. standards. But fewer understand Canadian ones. And while the U.S. standard may
seem tougher, the Canadians have a more practical view of the auditor's ability. © 2003 Wiley
Periodicals, Inc.
Why corporate reporting is a strategic opportunity
Authors: Thomas Alison
Published: October 2003

An activity that once seemed routine—corporate performance reporting—is now a strategic, evolving
concern. © 2003 Wiley Periodicals, Inc.
Cash is king: Cash management and risks
Authors: Goldberg Stephen R. , Godwin Joseph H.
Published: October 2003

Turner, Paul S. and Diane B. Wunnicke, 2003, Managing the Risks of Payment Systems (New
York: John Wiley & Sons).

Reider, Rob and Peter B. Heyler, 2003, Managing Cash Flow: An Operational Focus. (New
York: John Wiley & Sons).
Ion trap tandem mass spectrometric determination of F2‐isoprostanes
Authors: Signorini Cinzia , Comporti Mario , Giorgi Gianluca
Published: October 2003

A new tandem mass spectrometry (MS/MS) method based on the use of an ion trap mass spectrometer for the identification and quantitation of F2‐isoprostanes has been developed. It consists of two solid‐phase extractions and two derivation steps followed by gas chromatography/negative ion chemical ionization tandem mass spectrometry (GC/NICI‐MS/MS) analysis. This method is highly selective and sensitive and it has been successfully applied to biological samples. Copyright © 2003 John Wiley & Sons, Ltd.
Entropy evaluation using the kinetic method: is it feasible?
Authors: Drahos László , Vékey Károly
Published: October 2003

The kinetic method is one of the most widely used experimental techniques for the measurement of thermochemical parameters by mass spectrometry. Recently it has been realized that it can also be used to determine reaction entropies, but the validity of this approach has not been established. This Perspective evaluates kinetic method plots in cases where there is a significant entropy difference between the competing fragmentation channels (i.e. between sample and reference compounds in the dissociating cluster ion). The concept underlying this study is to calculate mass spectra theoretically, based on known thermochemical parameters and as a function of experimental conditions. This can be done accurately using the RRKM‐based MassKinetics software. The resulting mass spectra are then interpreted by the kinetic method, yielding ΔH and ΔS values. These values are, in turn, compared with the true values used to generate the calculated mass spectra. The results show that the reaction entropy difference between sample and reference has a very large influence on kinetic method plots. This should always be considered when studying energy‐dependent mass spectra (using metastable ions or low‐ or high‐energy collision‐induced dissociation (CID)), even if only ΔH is to be determined. Kinetic method plots are not strictly linear and this becomes a serious issue in the case of small molecules showing a large entropy effect. In such cases, results obtained at a low degree of excitation are more accurate. Energy and entropy effects can be evaluated in a relatively straightforward manner: first, the apparent Gibbs energy (ΔGapp) and effective temperature (Teff) are determined from kinetic method plots (intercept and slope, respectively), obtained from experiments using various degrees of excitation. Second, the resulting ΔGapp is plotted against Teff, the slope yielding ΔS while the intercept (extrapolation to zero temperature) yields ΔH. This data evaluation yields more accurate results than alternative methods used in the literature. The resulting ΔH values are fairly accurate, with errors, in most cases, <4 kJ mol−1. On the other hand, ΔS is systematically underestimated by 20–40%. Empirically scaling ΔS values determined by the kinetic method by 1.35 results in a ΔS value within 20% (or 10 J mol−1 K−1) of the theoretical value. Copyright © 2003 John Wiley & Sons, Ltd.
Insulin‐like actions of vanadium: Potential as a therapeutic agent
Authors: Marzban Lucy , McNeill John H.
Published: October 2003

Vanadium compounds are glucose‐lowering agents that are shown to mimic/enhance most of the metabolic actions of insulin both in vitro and in vivo. Several studies have demonstrated that vanadium treatment lowers plasma glucose levels in experimental models of type 1 diabetes and enhances insulin sensitivity in models of type 2 diabetes. Therefore, these compounds have gained attention as candidates for oral therapy in both types of diabetes. Despite numerous studies, the mechanism(s) by which vanadium mediates its metabolic effects in vivo are still not completely understood. The finding that most of the insulin‐like effects of vanadium in vitro are observed in the presence of high concentrations of vanadium that are not usually achieved in vivo suggests that these effects of vanadium may not have therapeutic relevance. Also, a growing body of evidence from in vivo studies indicates that enhancing glucose disposal in the peripheral tissues is not an adequate explanation for the glucose lowering effects of vanadium in vivo. Accordingly, recent studies suggest that suppression of hepatic glucose production through inhibition of key gluconeogenic enzymes might have an important role in mediating the glucoregulatory effects of vanadium. Several potential sites in the insulin‐signaling pathways, including both receptor and postreceptor mechanisms, have been proposed for the insulin‐like effects of vanadium compounds. In this review, we have attempted to discuss the possible molecular mechanism(s) underlying the metabolic effects of vanadium in vivo. J. Trace Elem. Exp. Med. 16:253–267, 2003. © 2003 Wiley‐Liss, Inc.
Recent advances in cellular iron metabolism
Authors: Ponka Prem
Published: October 2003

Iron is essential for oxidation–reduction catalysis and bioenergetics, but unless appropriately shielded, iron plays a key role in the formation of toxic oxygen radicals that can attack all biological molecules. Hence, specialized molecules for the acquisition, transport, and storage (ferritin) of iron in a soluble nontoxic form have evolved. The delivery of iron to most cells occurs after the binding of transferrin to transferrin receptors on the cell membrane. The transferrin receptor complexes are then internalized by endocytosis, and iron is released from transferrin by a process involving endosomal acidification. Iron is then transported through the endosomal membrane by the Fe2+ transporter Nramp2/DMT1. Importantly, the identical transporter is involved in the absorption of inorganic iron in the duodenum, a process that is facilitated by the ferric reductase, Dcytb, which provides Fe2+ for Nramp2/DMT1. Organisms and cells have limited ability to excrete excess iron and only some specialized cells evolved active mechanisms to export iron. Iron release from these “donor cells” (primarily enterocytes and macrophages that recycle hemoglobin iron) is mediated by ferroportin 1. The ferroxidase activity of copper‐containing proteins, hephaestin and ceruloplasmin, facilitates the movement of iron across the membranes of enterocytes and macrophages, respectively. Cells are also equipped with a regulatory system that controls iron levels in the labile pool. Levels of iron modulate the capacity of iron regulatory proteins to bind to the iron responsive elements present in the untranslated regions of mRNAs for several proteins involved in iron metabolism (e.g., ferritin, transferrin receptor, Nramp2); these associations, or lack of them, in turn control the expression of these proteins. Despite these homeostatic mechanisms, organisms often face the threat of either iron deficiency or iron overload. J. Trace Elem. Exp. Med. 16:201–217, 2003. © 2003 Wiley‐Liss, Inc.
Structure–activity relationship of insulinomimetic vanadyl–picolinate complexes in view of their clinical use
Authors: Sakurai Hiromu , Yasui Hiroyuki
Published: October 2003

In view of the clinical use of vanadium compounds, we prepared seven analogs of a vanadyl–picolinate complex (VO(pic)2) with VO(N2O2) coordination mode, which was found in 1995 to exhibit highly effective and long‐term insulinomimetic activity in treating both streptozotocin (STZ)‐induced type 1 diabetic rats (STZ rats) and hereditarily type 2 diabetic KK‐Ay mice by daily intraperitoneal (i.p.) injections and on oral administration, to find the structure–activity relationship of the complexes. Using an in vitro insulinomimetic evaluation of the complexes in terms of their inhibiting effect on free fatty acids release from isolated rat adipocytes treated with epinephrine (adrenaline), we found the activity (IC50: 50% inhibitor's concentration of the complex on the free fatty acid release) to be as follows: VO(5ipa)2 > VO(3mpa)2 > VO(6mpa)2 > VO(3hpa)2 > VO(pic)2 > VO(6hpa)2 ≈ VOSO4, indicating that the introduction of an electron‐withdrawing halogen atom or an electron‐donating methyl group at the 5th or 3rd position on the picolinate ligand causes stronger insulinomimetic activity than that of the lead complex VO(pic)2. Next we examined the pharmacokinetic features in the blood of the complexes by using the blood circulation‐monitoring electron spin resonance method, in which good linear relationships between the pharmacokinetic parameters and the IC50 values were found. Based on the results, we tested the complexes and found that both VO(5ipa)2 and VO(3mpa)2 complexes treat type 1 diabetes in STZ rats. Because the daily oral administration of vanadyl complexes is the only method to treat type 1 diabetes in place of daily insulin injections, the present results will be useful for the development of vanadyl complexes with high safety and long‐term activity. J. Trace Elem. Exp. Med. 16:269–280, 2003. © 2003 Wiley‐Liss, Inc.
Pre‐ and post‐transcriptional regulation of the Menkes disease gene
Authors: Harris Edward D. , Majumdar Sudeep
Published: October 2003

Menkes disease is testament to a copper (Cu)‐ATPase (ATP7A) playing a dominant role in the absorption and homeostasis of Cu. Significantly, the proximal promoter region of the Menkes disease gene (MNK) has cis‐active elements that relate to binding sites for transcription factors which in yeast are known to be activated by a low Cu status. A response to low Cu has not been rationalized into the control of Menkes gene expression, but seems important in light of recent Cu absorption studies in humans. The ATP7A gene gives rises to alternative transcripts, one of which has an insert at the 5′ end with sequence information for a protein with a structural domain similar to a Golgi tethering protein. This has opened speculation that one alternative transcript product may have an important biological function in regulating the entrance of ATP7A laded vesicles into the secretory pathway. This paper presents evidence supporting promoter activation and alternative splicing, pre‐ and post‐transcription events respectively, in the control of Menkes disease gene expression. J. Trace Elem. Exp. Med. 16:181–189, 2003. © 2003 Wiley‐Liss, Inc.
Recent advances in the biochemistry of chromium(III)
Authors: Vincent John B.
Published: October 2003

The biochemistry of chromium(III) [Cr(III)] has been a poorly understood field of endeavor; studies of the biochemistry of none of the other transition metals have been as problematic. Despite four decades of investigation, only recently has a clear picture of the role of Cr potentially been defined. The biologically important form is the trivalent ion. Cr(III) apparently is required for proper carbohydrate and lipid metabolism in mammals, although Cr deficiency is difficult to achieve. Conditions that increase circulating glucose and insulin concentrations increase urinary chromium output. Chromium is excreted after an insulin challenge, probably in the form of the oligopeptide chromodulin. Chromodulin may be the key to understanding the role of chromium at a molecular level as the molecule has been found to bind to activated insulin receptor, stimulating its kinase activity. A mechanism for the action of chromodulin has recently been proposed; this mechanism can serve as a potential framework for further studies to test the role of chromium in metabolism. An examination of the use of chromium picolinate, [Cr(pic)3], illustrates the difficulties associated with biochemical studies dealing with Cr(III). J. Trace Elem. Exp. Med. 16:227–236, 2003. © 2003 Wiley‐Liss, Inc.
Cadmium and human health: A perspective based on recent studies in China
Authors: Nordberg Gunnar
Published: October 2003

Cadmium (Cd) occurs in low concentrations in all human diets and in cigarettes. In contaminated areas and in certain occupations, high human exposures occur. In assessing risk to human health, it is important to identify the adverse effect that occurs at the lowest exposure level, i.e., the critical effect, which is crucial for preventive action. Excessive Cd exposure may give rise to renal, pulmonary, hepatic, skeletal, reproductive effects, and cancer. Previous evaluations (e.g., by WHO) have identified renal dysfunction, occurring in long‐term Cd exposure, as the critical effect. However, skeletal and reproductive effects are also discussed as possible critical effects. For preventive action, information is important about exposure levels that give rise to the earliest (critical) effects. To gain new information on this issue, population groups in China exposed to high concentrations of Cd via rice and Cd‐exposed workers were studied for possible renal, skeletal, and male reproductive toxicity. Skeletal effects in terms of decreased bone mineral density and an increased occurrence of fractures were found in groups of the general population living in the most Cd‐exposed area. Our studies further show that renal effects measured by sensitive biomarkers, such as urinary content of beta‐2‐microglobulin, calcium, and N‐acetyl‐beta‐D‐glucosaminidase, occurs at lower cumulative exposures to Cd than those giving rise to skeletal effects and also at lower exposures than previously estimated, e.g., by WHO. The findings confirm the renal dysfunction as the critical effect of long‐term Cd exposure. Metallothionein (MT) gene expression in peripheral blood lymphocytes was measured in Cd exposed workers. A higher prevalence of renal dysfunction was found among Cd exposed workers with low MT gene expression than among those with high MT gene expression, at similar blood and urinary Cd levels. MT gene expression in PBLC thus may be a biomarker for identifying sensitive population groups. J. Trace Elem. Exp. Med. 16:307–319, 2003. © 2003 Wiley‐Liss, Inc.
Regulation of tyrosine phosphorylation cascades by phosphatases: What the actions of vanadium teach us
Authors: Hulley Philippa , Davison Allan
Published: October 2003

Protein phosphorylation and dephosphorylation regulate much of the machinery of the cell. Emphasis in recent years has swung toward regulation by dephosphorylation. Much current research focuses on protein tyrosine phosphatases. Researchers of cellular regulation use vanadium as a probe because of its unparalleled ability to selectively inhibit protein tyrosine phosphatases at submicromolar concentrations. This review focuses on the biological actions of vanadium relevant to cellular regulatory cascades. Recent research has led to identification of control points and possible drug targets in 1) the glucose control mechanisms downstream from insulin receptors; 2) pathways regulating mitogenesis, tumor promotion, and other events downstream from growth factor receptors; 3) regulation of osteogenesis and possibilities for counteracting the bone damaging actions of glucocorticoids. An up‐to‐date understanding of the mechanisms by which vanadium acts and of its currently identified targets is prerequisite to the intelligent design of experiments of this kind. In this review, we will consider mechanisms at the enzymological level, in cellular regulatory cascades, and events affecting the cell or organism as a whole. J. Trace Elem. Exp. Med. 16:281–290, 2003. © 2003 Wiley‐Liss, Inc.
Dietary boron: An overview of the evidence for its role in immune function
Authors: Hunt Curtiss D.
Published: October 2003

This review summarizes the evidence for boron essentiality across the biological spectrum with special focus on biochemical pathways and biomolecules relevant to immune function. Boron is an essential trace element for at least some organisms in each of the phylogenetic kingdoms Eubacteria, Stramenopila (brown algae and diatoms), Viridiplantae (green algae and familiar green plants), Fungi, and Animalia. Discovery of several of the currently recognized boron‐containing biomolecules was achieved because the bound boron formed four coordinate covalent bonds with the ligand, creating a thermodynamically stable complex that is almost undissociable in water. Boron is a constitutive element in three antibiotics and a quorum‐sensing signal in bacteria. It enhances Fc receptor expression and interleukin‐6 production in cultured mammalian macrophages. Boron binds tightly to the diadenosine polyphosphates and inhibits the in vitro activities of various serine protease and oxidoreductase enzymes. Physiological amounts of dietary boron decrease skinfold thickness after antigen injection in gilts and elevated circulating natural killer cells after adjuvant injection in rats. It is predicted that several boron biomolecules waiting discovery are signaling molecules that interact with the cell surface and are probably composed of two mirror or near‐mirror halves stabilized by a single boron atom to form a large circular biomolecule. J. Trace Elem. Exp. Med. 16:291–306, 2003. Published 2003 Wiley‐Liss, Inc.
Zinc is essential for brain development and function
Authors: Sandstead Harold H.
Published: October 2003

Zinc's roles in brain function are poorly understood. Zinc is essential pre‐ and postnatally for growth, maturation, and function. In early pregnancy, zinc is essential for cell multiplication and implantation of the embryo and for cell differentiation and organ formation. Deficiency causes teratology in all tissues. Zn deficiency in later pregnancy impairs neuronal replication and migration (as observed in cerebellar external granular cells). Synaptogenesis is impaired (as observed in Purkinje cells). It has been proposed that zinc deficiency impairs calcium channels causing a decrease in intracellular calcium that suppresses gene expression of growth factors and synthesis of nucleic acids and proteins. Whatever the mechanism, effects in experimental animals include poorly reversible impairments in learning and memory later in life, which appears associated with decreased neuronal survival. It is unknown if similar phenomena occur in humans. It is known however that low fetal growth, a process caused by maternal zinc deficiency, is risk factor for coronary heart disease, type 2 diabetes mellitus, chronic lung disease, and obesity. One wonders if fetal growth is related to later neuronal health and function. J. Trace Elem. Exp. Med. 16:165–173, 2003. © 2003 Wiley‐Liss, Inc.
Gastrointestinal nematodes, trace elements, and immunity
Authors: Koski Kristine G. , Scott Marilyn E.
Published: October 2003

The exploration of the scientific literature on the interrelationship among trace elements, gastrointestinal nematodes, and their requisite Th2 immunity demonstrates extensive literature but regrettably, research remains inadequate and sparse, with far fewer studies having investigated the interrelationship among trace elements and host immunity in infected hosts. Gastrointestinal nematodes, such as hookworms, Ascaris lumbricoides, and Trichuris trichiura, require activation of the Th2 arm of the immune cascade and the expression of the Th2 cytokines (interleukin‐4, interleukin‐5, and interleukin‐10) and their effectors for worm expulsion. However, parasites have evolved a series of strategies to invade the host and to evade host defense mechanisms. Many of these mechanisms involve metalloproteinases for tissue invasion and enzymes, such as catalase and superoxide dismutase, to minimize free radical damage to the parasitic tissues from the host's immune system. Deficiencies of iron, molybdenum, copper, and zinc, have been associated with higher worm burdens, as have excessive intakes of molybdenum, iron, and copper. The possibility is emerging that there may be an optimum trace element level in the diet above which and below which the parasite is advantaged. Moreover, there is some data to suggest that specific trace elements may be directly toxic to the parasite. J. Trace Elem. Exp. Med. 16: 237–251, 2003. © 2003 Wiley‐Liss, Inc.
Arsenic essentiality: A role affecting methionine metabolism
Authors: Uthus Eric O.
Published: October 2003

Although there is no known biological function of arsenic, considerable evidence suggests that arsenic has a physiological role related to methionine metabolism. In early studies using amino acid‐based diets, it was found that arsenic deprivation had little effect on growth in rats fed adequate methionine. However, in rats fed suboptimal methionine, arsenic deprivation resulted in a significant reduction in body weight. Other studies showed that feeding methyl depletors caused severe signs of arsenic deprivation. Because it was found that alteration in methionine status or methyl metabolism affected signs of arsenic deprivation, and that many of these signs were related to methionine or methyl metabolism, it was hypothesized that arsenic has a physiological role affecting methionine metabolism. In animal studies testing this hypothesis, it was shown that arsenic deprivation reduces the hepatic concentration of S‐adenosylmethionine. Additionally, arsenic status affects DNA methylation in animal and cell culture models; very low or high doses of arsenic, compared with control amounts, result in an apparent hypomethylation of DNA. Because global DNA hypomethylation is associated with an increased incidence of cancer, we tested whether dietary arsenic (deficient, adequate, or excess; 0, 0.5 or 50 μg arsenic/g diet, respectively) would affect the formation of aberrant crypts in rats treated with the carcinogen dimethylhydrazine. Aberrant crypts are preneoplastic lesions that have been associated with colon carcinomas. More aberrant crypts were observed in rats fed the high amount of dietary arsenic compared to those fed adequate arsenic. The number of aberrant crypts in the arsenic‐deprived group also tended to be higher than those found in rats fed adequate arsenic. Thus, many findings indicate that arsenic plays a role in methionine/methyl metabolism; however, the site of action of arsenic remains unknown. Possibly, arsenic is instrumental in maintaining the metabolic pool of S‐adenosylmethionine. These results show that compared to controlled amounts, having too little or too much arsenic in the diet is harmful. That is, there is an amount of dietary arsenic that is not only not harmful, but beneficial. J. Trace Elem. Exp. Med. 16:345–355, 2003. Published 2003 Wiley‐Liss, Inc.
Copper‐lowering therapy with tetrathiomolybdate for cancer and diseases of fibrosis and inflammation
Authors: Brewer George J.
Published: October 2003

Angiogenesis is required for tumor growth and is a likely Achilles heel for cancer. However, antiangiogenic agents have been somewhat disappointing in cancer therapy, perhaps because they target a single angiogenic factor, and there is much redundancy in angiogenic systems. Copper is required for high levels of angiogenesis, and many angiogenic factors have a requirement for copper. Thus, anticopper drugs offer the possibility of more global inhibition. Our group has developed tetrathiomolybdate (TM) for the initial treatment of neurologic Wilson's disease. Penicillamine makes about 50% of these patients neurologically worse, and many never recover. Only 2 of 55 (3.6%) patients worsened when treated with TM. Because TM exhibited desirable properties of potency, speed, and safety, we studied it as an antiangiogenic agent. We hypothesize that if copper is lowered to midrange, the cellular requirements for copper are met, but angiogenic cytokine signaling is inhibited. TM has shown strong inhibition of cancer growth in five rodent models, encouraging results in a canine study of advanced and metastatic cancer, and encouraging results in a phase 1/2 study of advanced and metastatic cancer in 42 patients. Finally, we have hypothesized that the pathway of fibrosis involving transforming growth factor beta (TGF‐β) and connective tissue growth factor is inhibitable by copper‐lowering therapy with TM. This pathway is overactive and dysregulated in many diseases of fibrosis. In animal studies, TM has completely inhibited the pulmonary fibrosis induced by bleomycin, the hepatitis induced by concanavalin A, and the cirrhosis induced by carbon tetrachloride. We find that TM inhibits transforming growth factor beta and inflammatory cytokines tumor necrosis factor alpha and interleukin‐1‐beta. J. Trace Elem. Exp. Med. 16:191–199, 2003. © 2003 Wiley‐Liss, Inc.
Zinc status (plasma and hair zinc concentrations) during pregnancy: A longitudinal study
Authors: Çavdar A.O. , Söylemez F. , Cengiz B. , Aydemir F.
Published: October 2003

A longitudinal study of plasma and hair zinc concentration analysis was performed in 51 and 38 pregnant women, respectively. Plasma zinc levels were followed from first trimester to the end of second trimester, whereas hair zinc concentrations were measured in all trimesters. They were all measured by atomic absorption spectrophotometer. Both plasma and hair zinc levels declined significantly during the second trimesters There was also a significant difference in plasma zinc levels between the “well‐nourished” and “poorly nourished” groups (P < 0.001 and P < 0.05)Similar changes could not be observed for hair zinc concentrations, probably because of the fact that all pregnant women were from Ankara rather than from villages, where the dietary habit is frequently associated with zinc deficiency. J. Trace Elem. Exp. Med. 16:175–179, 2003. © 2003 Wiley‐Liss, Inc.
An overview of the role of iron in T cell activation
Authors: Kuvibidila Solo , Warrier Raj P. , Surendra Baliga B.
Published: October 2003

Iron, an essential growth trace element, is required for proliferation of all living cells, including T lymphocytes. Many, though not all, immune responses require lymphocyte proliferation. Iron deficiency, a worldwide public health problem for children and for women of childbearing age, is associated with impaired lymphocyte proliferative responses to mitogens and cell‐mediated immunity. However, the mechanisms have not been fully elucidated. Our data on certain early key events in the T cell activation pathways, obtained from iron‐deficient murine splenic T lymphocytes, show reductions in hydrolysis of cell membrane phosphatidyl inositol 4,5 bisphosphate, protein kinase C activation, and interleukin‐2 secretion. Although the expression of CD3 molecule (a component of the T cell‐receptor/CD3 complex, required for T cell activation) is not decreased by iron deficiency in splenocytes and thymocytes, the expression of the co‐stimulatory molecule, CD28, is. Iron‐deficiency increases the percentage of CD3+/CD28− thymocytes but decreases that of CD3−/CD28+ cells. Iron deficiency and iron chelation by deferoxamine decrease CD28 fluorescence intensity but tends to increase that of CD3. Progression of activated spleen cells through the cell cycle (Go/G1, S, G2/M phases) is also altered by iron deficiency independently of differences in the percentages of CD3+ T cells between groups, probably through impaired transition of G1 to S phase. Data suggest that the role of iron in T cell proliferation is not limited to the regulation of ribonucleotide reductase activity, but also involves other steps in the T cell activation pathways. J. Trace Elem. Exp. Med. 16:219–225, 2003. © 2003 Wiley‐Liss, Inc.
Zinc and immunity: Molecular mechanisms of zinc action on T helper cells
Authors: Prasad Ananda S.
Published: October 2003

The essentiality of zinc for humans was recognized in 1963. It is now evident that nutritional deficiency of zinc in human populations throughout the developing world is common. The major factor responsible for this deficiency is the consumption of mainly cereal proteins rich in phytate. The clinical manifestations of zinc deficiency include growth retardation and male hypogonadism in the adolescents, rough skin, poor appetite, mental lethargy, delayed wound healing, cell‐mediated immune dysfunctions, and abnormal neurosensory disorders. A conditioned deficiency of zinc has been observed in many diseased states. In this work I have summarized our current knowledge concerning the molecular mechanisms of zinc action on T helper cells. Our studies showed that in zinc‐deficient HUT‐78 cells, phosphorylated IκB and Iκk, ubiquitinated IκB, and binding of nuclear factor (NF)‐κB to DNA were significantly decreased. Zinc increased the translocation of NF‐κB from cytosol to nucleus. These data show that zinc plays an important role in the activation of NF‐κB in HUT‐78 cells. We showed a significant effect of zinc on gene expression of interleukin (IL)‐2 and IL‐2 receptors α and β. We also showed that a decrease in gene expression of IL‐2 and its receptors in zinc‐deficient HUT‐78 cells may be the result of decreased activation of NF‐κB in zinc‐deficient cells. J. Trace Elem. Exp. Med. 16:139–163, 2003. © 2003 Wiley‐Liss, Inc.
On non‐normal del Pezzo surfaces
Authors: Abe Makoto , Furushima Mikio
Published: October 2003

LetYbe a non‐normal del Pezzo surface over ℂ and letd≔ (ω−1Y)2> 0 be the degree ofY. Then we prove thatω⊗d−4Yis very ample ford= 1, 2.
A matriceal analogue of Fejer's theory
Authors: Barza Sorina , Persson Lars‐Erik , Popa Nicolae
Published: October 2003

J. Arazy [1] pointed out that there is a similarity between functions defined on the torus and infinite matrices. In this paper we discuss and develop in the framework of matrices Fejer's theory for Fourier series.
Intrinsic characterizations of Besov spaces on Lipschitz domains
Authors: Dispa Sophie
Published: October 2003

The aim of this paper is to study the equivalence between quasi‐norms of Besov spaces on domains. We suppose that the domain Ω ⊂ ℝn is a bounded Lipschitz open subset in ℝn. First, we define Besov spaces on Ω as the restrictions of the corresponding Besov spaces on ℝn. Then, with the help of equivalent and intrinsic characterizations (the Peetre‐type characterization 3.10 and the characterization via local means 3.13) of these spaces, we get another equivalent and intrinsic quasi‐norm using, this time, generalized differences and moduli of smoothness. We extend the well‐known characterization of Besov spaces on ℝn described in Theorem 2.4 to the case of Lipschitz domains.
Analytical properties of measure geometric Krein‐Feller‐operators on the real line
Authors: Freiberg Uta
Published: October 2003

We investigate analytical properties of a measure geometric Laplacian which is given as the second derivative $ {d \over {d \mu}} {d \over {d \nu}} $ w.r.t. two atomless finite Borel measures μ and ν with compact supports supp μ ⊂ supp ν on the real line. This class of operators includes a generalization of the well‐known Sturm‐Liouville operator $ {d \over {d \mu}} {d \over {dx}} $ as well as of the measure geometric Laplacian given by $ {d \over {d \mu}} {d \over {d \mu}} $. We obtain for this differential operator under both Dirichlet and Neumann boundary conditions similar properties as known in the classical Lebesgue case for the euclidean Laplacian like Gauß‐Green‐formula, inversion formula, compactness of the resolvent and its kernel representation w.r.t. the corresponding Green function. Finally we prove nuclearity of the resolvent and give two representations of its trace.
On the index of a vector field tangent to a hypersurface with non‐isolated zero in the embedding space
Authors: Klehn Oliver
Published: October 2003

We give a generalization of an algebraic formula of Gomez‐Mont for the index of a vector field with isolated zero in (ℂn, 0) and tangent to an isolated hypersurface singularity. We only assume that the vector field has an isolated zero on the singularity here.
Blow up and global existence in a nonlinear viscoelastic wave equation
Authors: Messaoudi Salim A.
Published: October 2003

In this paper the nonlinear viscoelastic wave equation

associated with initial and Dirichlet boundary conditions is considered. Under suitable conditions on g, it is proved that any weak solution with negative initial energy blows up in finite time if p > m. Also the case of a stronger damping is considered and it is showed that solutions exist globally for any initial data, in the appropriate space, provided that m ≥ p.
Intersection theory for loaded cycles IV — resonant cases
Authors: Mimachi Katsuhisa , Ochiai Hiroyuki , Yoshida Masaaki
Published: October 2003

We study the structure of the twisted homology groups attached to weighted lines in the plane with resonant singular points, and find possible intersection pairings. As a typical example, we treat homology groups attached to 2‐dimensional Selberg‐type integrals.
On the spectral norm of algebraic numbers
Authors: Popescu Angel , Popescu Nicolae , Zaharescu Alexandru
Published: October 2003

In this paper we continue to study the spectral norms and their completions ([4]) in the case of the algebraic closure \documentclass{article} \usepackage{amssymb} \pagestyle{empty} \begin{document} $ \overline {\mathbb Q} $ \end{document} of ℚ in ℂ. Let \documentclass{article} \usepackage{amssymb} \pagestyle{empty} \begin{document} $ \widetilde{\overline{\mathbb{Q}}} $ \end{document} be the completion of \documentclass{article} \usepackage{amssymb} \pagestyle{empty} \begin{document} $ \overline {\mathbb Q} $ \end{document} relative to the spectral norm. We prove that \documentclass{article} \usepackage{amssymb} \pagestyle{empty} \begin{document} $ \widetilde{\overline{\mathbb{Q}}} $ \end{document} can be identified with the R‐subalgebra of all symmetric functions of C(G), where C(G) denotes the ℂ‐Banach algebra of all continuous functions defined on the absolute Galois group G = Gal\documentclass{article} \usepackage{amssymb} \pagestyle{empty} \begin{document} $ {\overline {\mathbb Q}} / {\mathbb Q} $ \end{document}. We prove that any compact, closed to conjugation subset of ℂ is the pseudo‐orbit of a suitable element of \documentclass{article} \usepackage{amssymb} \pagestyle{empty} \begin{document} $ \widetilde{\overline{\mathbb{Q}}} $ \end{document}. We also prove that the topological closure of any algebraic number field in \documentclass{article} \usepackage{amssymb} \pagestyle{empty} \begin{document} $ \widetilde{\overline{\mathbb{Q}}} $ \end{document} is of the form \documentclass{article} \usepackage{amssymb} \pagestyle{empty} \begin{document} $\widetilde{\mathbb{Q}[x]}$ \end{document} with x in \documentclass{article} \usepackage{amssymb} \pagestyle{empty} \begin{document} $ \widetilde{\overline{\mathbb{Q}}} $ \end{document}.
On the braid index of θm‐curve in 3‐space
Authors: Shinnoki Tomoko , Takamuki Takashi
Published: October 2003

In this paper we consider the braid index and the number of Seifert circles of a θm‐curve in ℝ3 as a generalization of the concepts on an oriented link and establish a relation between them and the degree of Yokota's polynomial invariant.
An algorithm for the divisors of monic polynomials over a commutative ring
Authors: Yengui Ihsen
Published: October 2003

Gilmer and Heinzer proved that given a reduced ring R, a polynomial f divides a monic polynomial in R[X] if and only if there exists a direct sum decomposition of R = R0 ⊕ … ⊕ Rm (m ≤ deg f), associated to a fundamental system of idempotents e0, … , em, such that the component of f in each Ri[X] has degree coefficient which is a unit of Ri. We propose to give an algorithm to explicitly find such a decomposition. Moreover, we extend this result to divisors of doubly monic Laurent polynomials.
Mechanisms of inactivation of the p16INK4a gene in leiomyosarcoma of soft tissue: decreased p16 expression correlates with promoter methylation and poor prognosis
Authors: Kawaguchi Ken‐ichi , Oda Yoshinao , Saito Tsuyoshi , Yamamoto Hidetaka , Tamiya Sadafumi , Takahira Tomonari , Miyajima Kimitaka , Iwamoto Yukihide , Tsuneyoshi Masazumi
Published: October 2003

The p16INK4a tumour suppressor gene, encoding p16 protein, plays a crucial role in regulation of the G1 cell‐cycle phase. To investigate the potential role of p16 in soft tissue leiomyosarcoma (LMS), an immunohistochemical analysis was performed of 77 LMSs for p16 expression. Decreased expression of the p16 protein was identified in 25 of 77 LMSs (32%). Decreased expression of p16 correlated significantly with large tumour size (p = 0.0038). In a univariate analysis, large tumour size and decreased expression of p16 were statistically significant adverse prognostic factors (p = 0.025 and p = 0.0021, respectively). In a multivariate analysis including conventional clinicopathological parameters, decreased expression of p16 protein was revealed as the only independent unfavourable prognostic factor (p = 0.012). To elucidate the mechanisms of inactivation of the p16INK4a gene, 49 LMSs for which genomic DNA was available were examined; analysis for homozygous deletion, mutation, and promoter hypermethylation was conducted using differential PCR, PCR–SSCP, and methylation‐specific PCR, respectively. Promoter hypermethylation was detected in 11 of 49 LMS cases (22%); homozygous deletion was detected in 3 of 49 cases (6%); and mutation was not recognized in any of the cases studied. Eight of 15 cases (53%) with decreased expression of p16 protein revealed methylation of the p16INK4a gene promoter. Promoter hypermethylation correlated closely with decreased expression and poor prognosis (p = 0.0014 and p = 0.0088, respectively). These results suggest that decreased expression of p16 protein can be considered as an independent reliable prognostic parameter in patients with soft tissue LMS. Furthermore, promoter methylation was more frequent than either homozygous deletion or mutation in this tumour, and promoter methylation was also shown to have a strong association with inactivation of the p16INK4a gene. Copyright © 2003 John Wiley & Sons, Ltd.
NF‐κB expression in oral and cutaneous lichen planus
Authors: Santoro Amerigo , Majorana Alessandra , Bardellini Elena , Festa Silvana , Sapelli Pierluigi , Facchetti Fabio
Published: October 2003

Lichen planus (LP) is a chronic inflammatory disorder involving cutaneous and mucosal surfaces, characterized by a T‐cell‐mediated immune response against epithelial cells, with persistent accumulation of T lymphocytes and epithelial cell damage. The mechanisms involved in this chronic inflammatory disease are largely unknown. A pivotal role in the pathogenesis of long‐lasting inflammatory processes is played by the activation of nuclear factor kappa B (NF‐κB), a primary transcription factor which upon translocation to the nucleus, binds to promoter regions of different genes encoding immune and pro‐inflammatory mediators. Using immunohistochemistry, the present study analysed the expression of NF‐κB in 25 cases of cutaneous LP (CLP) and 28 cases of oral LP (OLP) and correlated this with the recruitment of cytotoxic T‐cells (expressing Tia‐1 or perforin) in the inflammatory infiltrate. Nuclear NF‐κB was expressed on basal and suprabasal keratinocytes in all cases of LP, while normal epithelium was consistently negative; OLP contained significantly higher numbers of NF‐κB‐positive keratinocytes than CLP (means: 89.32 versus 22.6; p < 0.05). Furthermore, nuclear NF‐κB expression by epithelial cells correlated with the amount of cytotoxic cell infiltration (p < 0.02). These data suggest that increased NF‐κB activity may represent the basis of maintenance of the inflammatory response. The differences observed between NF‐κB expression on epithelial cells in OLP and CLP and their correlation with the degree of cytotoxic inflammatory infiltrate might explain the different clinical courses of the two variants of the disease, since OLP is typically more recalcitrant than CLP. As proposed for other chronic inflammatory disorders associated with increased NF‐κB activity, the involvement of NF‐κB in the pathogenesis of LP could be considered for selective therapeutic inhibitory targeting. Copyright © 2003 John Wiley & Sons, Ltd.
Expression of the thioredoxin system in interstitial lung disease
Authors: Tiitto Leena , Kaarteenaho‐Wiik Riitta , Sormunen Raija , Holmgren Arne , Pääkkö Paavo , Soini Ylermi , Kinnula Vuokko L
Published: October 2003

The thioredoxin system containing thioredoxin (Trx) and thioredoxin reductase (TrxR) has profound effects on cell proliferation and protection against exogenous oxidants. The significance of the Trx system in human lung and lung diseases is, however, largely unresolved. Altogether, 66 specimens of human lung were investigated by immunohistochemistry for their expression of Trx and TrxR. The diseases included interstitial pneumonias such as usual interstitial pneumonia (UIP), desquamative interstitial pneumonia (DIP), and UIP associated with collagen vascular diseases (CVD‐ILD), and granulomatous diseases such as sarcoidosis and allergic alveolitis. The ultrastructural localization of Trx and TrxR was analysed by immunoelectron microscopy. In healthy lung, Trx and TrxR were expressed in bronchial epithelium and alveolar macrophages. Trx and TrxR were highly concentrated in areas of metaplastic epithelium in UIP and in alveolar macrophages in DIP, though fibrotic areas in UIP were mainly negative. The expression of both enzymes was clearly weaker in CVD‐ILD than in UIP. Granulomas of sarcoidosis showed moderate to intense Trx immunoreactivity. Ultrastructurally, Trx and TrxR were expressed diffusely in the cytosolic compartment and plasma membrane of metaplastic type II pneumocytes, macrophages, and bronchial epithelial cells. This study highlights the importance of Trx and TrxR in primary defence in bronchial epithelium, alveolar epithelium, and macrophages in human lung, but also indicates that elevated expression of these proteins may serve as markers of ongoing cell regeneration and inflammation. Copyright © 2003 John Wiley & Sons, Ltd.
Tissue‐specific p53 responses to ionizing radiation and their genetic modification: the key to tissue‐specific tumour susceptibility?
Authors: Coates Philip J , Lorimore Sally A , Lindsay Kirsten J , Wright Eric G
Published: October 2003

Although little is understood of the underlying mechanisms, there are tissue‐specific responses to tumourigenic and therapeutic agents and these responses are influenced by genetic factors. Ionizing radiation is an important tumourigenic and therapeutic agent for which there is substantial evidence for such tissue‐dependent and genotype‐dependent responses. Because the p53 tumour suppressor protein is a major determinant of cellular responses to radiation, the present study has investigated whether modification of the p53 pathway contributes to tissue‐dependent and genotype‐dependent responses using inbred strains of mice. Comparison of responses in haemopoietic and epithelial cells in irradiated C57BL/6 and DBA/2 mice revealed significant differences in p53 and apoptotic responses in different cell types and in different cells of the same type, reflecting the complexity of damage responses operating in the whole organism. The data suggest that p53‐mediated up‐regulation of Bax is a major determinant of apoptosis in the spleen, but not in the intestine, whereas p53‐mediated induction of p21waf1 plays an anti‐apoptotic role in the spleen, but not in the intestine. It is also shown that p53 stabilization and differential transactivational activities towards Bax or p21waf1 are influenced by genetic factors that act in a tissue‐specific manner. Analysis of ATM, a potential mediator of differential p53 activation, indicates that this key regulator of radiation responses is preferentially induced in epithelial cells, but is unlikely to account for genetic modification of p53 or apoptotic responses in the mouse strains studied. Polymorphisms in the p53 or DNA‐PKcs genes are also unlikely to account for the genetic modifications that are reported here. There are numerous further potential modifiers of the p53 pathway, but analysis of backcross and inter‐cross mice demonstrates that genes responsible for the complex modification of these in vivo responses can be identified by linkage analysis. This approach has the potential to reveal new or unexpected interactions involving the p53 pathway that determine both short‐term and long‐term effects of radiation exposure and the basis of tissue‐specific responses and tumour susceptibility. Copyright © 2003 John Wiley & Sons, Ltd.