bluuebunny/crossref_metadata_2025 huggingface dataset:
Photosynthesis and carbon balance of a Sahelian fallow savanna
Authors: Hanan Niall P. , Kabat Pavel , Dolman A. Johannes , Elbers JaN. A.
Published: October 2003

Eddy‐covariance measurements of CO2 exchange above a Sahelian savanna consisting of small shrubs over a near‐continuous herb layer were made during the HAPEX‐Sahel experiment in Niger, West Africa. The measurements were made near‐continuously during an 8‐week period, covering the main part of the rainy season and three weeks at the beginning of the dry season. The measurements were corrected for in‐canopy storage of CO2 and the night‐time measurements used to derive respiration functions for the soil, roots and above‐ground plant material. Photosynthetic CO2 uptake was estimated and compared to simulations using a biochemical photosynthesis model in a simple, ‘big‐leaf’, implementation. The model satisfactorily reproduced the measurements (coefficient of determination 0.80) using parameters defined from the literature and based on soil nutrient concentrations. When the quantum yield (α) and rubisco capacity (Vmr) were fitted to the data with allowance for physiological changes through the season, an excellent agreement between model and measurements was obtained (coefficient of determination 0.93, RMS error 1.46 μmol m–2 s–1).

The fitted photosynthesis and respiration model was used to estimate the carbon balance of the savanna site during the growing season of 1992 and for the complete calendar year. Harvest estimates of net plant biomass accumulation during the growing season and annual wood accumulation agreed well with modelled net photosynthesis and annual net carbon accumulation, respectively. Peak instantaneous ecosystem CO2 uptake was comparable to peak values observed in other biomes, but annual photosynthesis and carbon sequestration were considerably lower than observed elsewhere.
Potentially complex biosphere responses to transient global warming
Authors: Neilson Ronald P. , Drapek Raymond J.
Published: October 2003

Feedback interactions between terrestrial vegetation and climate could alter predictions of the responses of both systems to a doubling of atmospheric CO2. Most previous analyses of biosphere responses to global warming have used output from equilibrium simulations of current and future climate, as compared to more recently available transient GCM simulations. We compared the vegetation responses to these two different classes of GCM simulation (equilibrium and transient) using an equilibrium vegetation distribution model, MAPSS. Average climatologies were extracted from the transient GCM simulations for current and doubled (2×) CO2 concentrations (taken to be 2070–2099) for use by the equilibrium vegetation model. However, the 2 × CO2 climates extracted from the transient GCM simulations were not in equilibrium, having attained only about 65% of their eventual 2 × CO2 equilibrium temperature change. Most of the differences in global vegetation response appeared to be related to a very different simulated change in the pole to tropic temperature gradient. Also, the transient scenarios produced much larger increases of precipitation in temperate latitudes, commensurate with a minimum in the latitudinal temperature change. Thus, the (equilibrium) global vegetation response, under the transient scenarios, tends more to a greening than a decline in vegetation density, as often previously simulated. It may be that much of the world could become greener during the early phases of global warming, only to reverse in later, more equilibrial stages. However, whether or not the world's vegetation experiences large drought‐induced declines or perhaps large vegetation expansions in early stages could be determined by the degree to which elevated CO2 will actually benefit natural vegetation, an issue still under debate. There may occur oscillations, perhaps on long timescales, between greener and drier phases, due to different frequency responses of the coupled ocean–atmosphere–biosphere interactions. Such oscillations would likely, of themselves, impart further reverberations to the coupled Earth System.
An internet retailing data framework for supporting consumers and business processes
Authors: Vrechopoulos Adam P. , Pramataris Katherine C. , Doukidis Georgios , Lekakos George
Published: October 2003

Abstract.  This paper describes an action research case study dealing with the development of an internet retail store with advanced capabilities. The research focuses on the exploitation of information generated through consumer–system interaction by the virtual retailer (i.e. sales, navigation and personal consumer data). The results effectively support the business processes, consumers and product suppliers. To that end, an internet retailing data framework was developed during the user requirements capturing phase of the ACTIVE (Advertising and Commerce Through the Internet in the context of the Virtual Enterprise) project, as a means of structuring the system's information requirements and data processing mechanisms. The purpose of this framework is to describe in detail what consumer information the system needs to collect and to advise the virtual retailer (i.e. ACTIVE's administrator) how to use the available software components to exploit this information in order to effectively support consumers and business processes. Despite the fact that the proposed framework is tailored to the ACTIVE characteristics and needs, it can also be utilized by other virtual retailers to effectively support their key stakeholders (i.e. customers and suppliers).
The 2G method for doubly grounding evaluation frameworks
Authors: Lundell Björn , Lings Brian
Published: October 2003

Abstract.  There are a number of approaches open to an information system (IS) development organization wishing to evaluate the potential relevance of an IT product for use in their own organization. This work considers method support for evaluation of CASE tools, as a complex example of an IT product. Our interest is in evaluation for selection, namely the evaluation of products prior to experience of their use in the defined context. Certain weaknesses are apparent in existing evaluation methods proposed in the literature for evaluation for selection. Our primary concern in this paper is to present a new method which, we claim, addresses these weaknesses. We provide a rationale and a detailed description of the new method, which is referred to as 2G. The method specifically addresses the important early phases of an evaluation, during which an evaluation framework is to be established. The method is to be used within the intended usage context for the IT product, so the resulting evaluation framework will be situated rather than general. We identify weaknesses in previously available methods, and discuss the advantages offered by the 2G method. The method has a solid basis in underlying theory, something which has influenced our presentation of it. Equally importantly, our presentation is strongly influenced by our experience with the method in actual usage situations, in small and medium IS development organizations. We claim that 2G is a practical candidate for any IS development organization wishing to undertake evaluations of CASE tools prior to adoption.
Human aquaporin adipose (AQPap) gene
Authors: Kondo Hidehiko , Shimomura Iichiro , Kishida Ken , Kuriyama Hiroshi , Makino Yasunaka , Nishizawa Hitoshi , Matsuda Morihiro , Maeda Norikazu , Nagaretani Hiroyuki , Kihara Shinji , Kurachi Yoshihisa , Nakamura Tadashi , Funahashi Tohru , Matsuzawa Yuji
Published: October 2003

Aquaporin adipose (AQPap), which we identified from human adipose tissue, is a glycerol channel in adipocyte [Kishida et al. (2000) J. Biol. Chem.275, 20896–20902]. In the current study, we determined the genomic structure of the human AQPap gene, and identified three AQPap‐like genes that resembled (≈ 95%) AQPap, with little expression in human tissues. The AQPap promoter contained a putative peroxisome proliferator response element (PPRE) at −46 to −62, and a putative insulin response element (IRE) at −542/−536. Deletion of the PPRE abolished the pioglitazone‐mediated induction of AQPap promoter activity in 3T3‐L1 adipocytes. Deletion and single base pair substitution analysis of the IRE abolished the insulin‐mediated suppression of the human AQPap gene. Analysis of AQPap sequence in human subjects revealed three missense mutations (R12C, V59L and G264V), and two silent mutations (A103A and G250G). The cRNA injection of the missense mutants into Xenopus oocytes revealed the absence of the activity to transport glycerol and water in the AQPap‐G264V protein. In the subject homozygous for AQPap‐G264V, exercise‐induced increase in plasma glycerol was not observed in spite of the increased plasma noradrenaline. We suggest that AQPap is responsible for the increase of plasma glycerol during exercise in humans.
The fate of newly synthesized V‐ATPase accessory subunit Ac45 in the secretory pathway
Authors: Schoonderwoert Vincent Th. G. , Jansen Eric J. R. , Martens Gerard J. M.
Published: October 2003

The vacuolar H+‐ATPase (V‐ATPase) is a multimeric enzyme complex that acidifies organelles of the vacuolar system in eukaryotic cells. Proteins that interact with the V‐ATPase may play an important role in controlling the intracellular localization and activity of the proton pump. The neuroendocrine‐enriched V‐ATPase accessory subunit Ac45 may represent such a protein as it has been shown to interact with the membrane sector of the V‐ATPase in only a subset of organelles. Here, we examined the fate of newly synthesized Ac45 in the secretory pathway of a neuroendocrine cell. A major portion of intact ≈ 46‐kDa Ac45 was found to be N‐linked glycosylated to ≈ 62 kDa and a minor fraction to ≈ 64 kDa. Trimming of the N‐linked glycans gave rise to glycosylated Ac45‐forms of ≈ 61 and ≈ 63 kDa that are cleaved to a C‐terminal fragment of 42–44 kDa (the deglycosylated form is ≈ 23 kDa), and a previously not detected ≈ 22‐kDa N‐terminal cleavage fragment (the deglycosylated form is ≈ 20 kDa). Degradation of the N‐terminal fragment is rapid, does not occur in lysosomes and is inhibited by brefeldin A. Both the N‐ and C‐terminal fragment pass the medial Golgi, as they become partially endoglycosidase H resistant. The Ac45 cleavage event is a relatively slow process (half‐life of intact Ac45 is 4–6 h) and takes place in the early secretory pathway, as it is not affected by brefeldin A and monensin. Tunicamycin inhibited N‐linked glycosylation of Ac45 and interfered with the cleavage process, suggesting that Ac45 needs proper folding for the cleavage to occur. Together, our results indicate that Ac45 folding and cleavage occur slowly and early in the secretory pathway, and that the cleavage event may be linked to V‐ATPase activation.
The solution structure of reduced dimeric copper zinc superoxide dismutase
Authors: Banci Lucia , Bertini Ivano , Cramaro Fiorenza , Del Conte Rebecca , Viezzoli Maria Silvia
Published: October 2003

The solution structure of homodimeric Cu2Zn2 superoxide dismutase (SOD) of 306 aminoacids was determined on a 13C, 15N and 70% 2H labeled sample. Two‐thousand eight‐hundred and five meaningful NOEs were used, of which 96 intersubunit, and 115 dihedral angles provided a family of 30 conformers with an rmsd from the average of 0.78 ± 0.11 and 1.15 ± 0.09 Å for the backbone and heavy atoms, respectively. When the rmsd is calculated for each subunit, the values drop to 0.65 ± 0.09 and 1.08 ± 0.11 Å for the backbone and heavy atoms, respectively.

The two subunits are identical on the NMR time scale, at variance with the X‐ray structures that show structural differences between the two subunits as well as between different molecules in the unit cell. The elements of secondary structure, i.e. eight β sheets, are the same as in the X‐ray structures and are well defined. The odd loops (I, III and V) are well resolved as well as loop II located at the subunit interface. On the contrary, loops IV and VI show some disorder. The residues of the active cavity are well defined whereas within the various subunits of the X‐ray structure some are disordered or display different orientation in different X‐ray structure determinations. The copper(I) ion and its ligands are well defined. This structure thus represents a well defined model in solution relevant for structure–function analysis of the protein. The comparison between the solution structure of monomeric mutants and the present structure shows that the subunit–subunit interactions increase the order in loop II. This has the consequences of inducing the structural and dynamic properties that are optimal for the enzymatic function of the wild‐type enzyme. The regions 37–43 and 89–95, constituting loops III and V and the initial part of the β barrel and showing several mutations in familial amyotrophis lateral sclerosis (FALS)‐related proteins have a quite extensive network of H‐bonds that may account for their low mobility. Finally, the conformation of the key Arg143 residue is compared to that in the other dimeric and monomeric structures as well as in the recently reported structure of the CCS–superoxide dismutase (SOD) complex.
A point mutation in the ATP synthase of Rhodobacter capsulatus results in differential contributions of ΔpH and Δφ in driving the ATP synthesis reaction
Authors: Turina Paola , Melandri B. Andrea
Published: October 2003

The interface between the c‐subunit oligomer and the a subunit in the F0 sector of the ATP synthase is believed to form the core of the rotating motor powered by the protonic flow. Besides the essential cAsp61 and aArg210 residues (Escherichia coli numbering), a few other residues at this interface, although nonessential, show a high degree of conservation, among these aGlu219. The homologous residue aGlu210 in the ATP synthase of the photosynthetic bacterium Rhodobacter capsulatus has been substituted by a lysine. Inner membranes prepared from the mutant strain showed approximately half of the ATP synthesis activity when driven both by light and by acid‐base transitions. As estimated with the ACMA assay, proton pumping rates in the inner membranes were also reduced to a similar extent in the mutant. The most striking impairment of ATP synthesis in the mutant, a decrease as low as 12 times as compared to the wild‐type, was observed in the absence of a transmembrane electrical membrane potential (Δφ) at low transmembrane pH difference (ΔpH). Therefore, the mutation seems to affect both the mechanism responsible for coupling F1 with proton translocation by F0, and the mechanism determining the relative contribution of ΔpH and Δφ in driving ATP synthesis.
Molecular cloning of the Matrix Gla Protein gene from Xenopus laevis
Authors: Conceição Natércia , Henriques Nuno M. , Ohresser Marc C. P. , Hublitz Philip , Schüle Roland , Cancela M. Leonor
Published: October 2003

To analyze the regulation of Matrix Gla Protein (MGP) gene expression in Xenopus laevis, we cloned the xMGP gene and its 5′ region, determined their molecular organization, and characterized the transcriptional properties of the core promoter. The Xenopus MGP (xMGP) gene is organized into five exons, one more as its mammalian counterparts. The first two exons in the Xenopus gene encode the DNA sequence that corresponds to the first exon in mammals whereas the last three exons show homologous organization in the Xenopus MGP gene and in the mammalian orthologs. We characterized the transcriptional regulation of the xMGP gene in transient transfections using Xenopus A6 cells. In our assay system the identified promoter was shown to be transcriptionally active, resulting in a 12‐fold induction of reporter gene expression. Deletional analysis of the 5′ end of the xMGP promoter revealed a minimal activating element in the sequence from −70 to −36 bp. Synthetic reporter constructs containing three copies of the defined regulatory element delivered 400‐fold superactivation, demonstrating its potential for the recruitment of transcriptional activators. In gel mobility shift assays we demonstrate binding of X. laevis nuclear factors to an extended regulatory element from −180 to −36, the specificity of the interaction was proven in competition experiments using different fragments of the xMGP promoter. By this approach the major site of factor binding was demonstrated to be included in the minimal activating promoter fragment from −70 to −36 bp. In addition, in transient transfection experiments we could show that this element mediates calcium dependent transcription and increasing concentrations of extracellular calcium lead to a significant dose dependent activation of reporter gene expression.
Epoxidation of benzo[a]pyrene‐7,8‐dihydrodiol by human CYP1A1 in reconstituted membranes
Authors: Kisselev Pyotr , Schwarz Dieter , Platt Karl‐Ludwig , Schunck Wolf‐Hagen , Roots Ivar
Published: October 2003

Human cytochrome P4501A1 (CYP1A1) is one of the key enzymes in the bioactivation of environmental pollutants such as benzo[a]pyrene (B[a]P) and other polycyclic aromatic hydrocarbons. To evaluate the effect of membrane properties and distinct phospholipids on the activity of human CYP1A1 purified insect cell‐expressed human CYP1A1 and of human NADPH‐P450 reductase were reconstituted into phospholipid vesicle membranes. Conversion rates of up to 36 pmol·min−1·pmol−1 CYP1A1 of the enantiomeric promutagens (–)‐ and (+)‐trans‐7,8‐dihydroxy‐7,8‐dihydro‐B[a]P (7,8‐diol) to the genotoxic diolepoxides were achieved. The highest rates were obtained when negatively charged lipids such as phosphatidylserine and phosphatidylinositol and/or nonbilayer phospholipids such as phosphatidylethanolamine were present in the membrane together with neutral lipids. Both Vmax and Km values were changed. This suggests a rather complex mechanism of stimulation which might include altered substrate binding as well as more effective interaction between CYP1A1 and NADPH‐P450 reductase. Furthermore, the ratio of r‐7,t‐8‐dihydroxy‐t‐9,10‐epoxy‐7,8,9,10‐tetrahydro‐B[a]P (DE2) to r‐7,t‐8‐dihydroxy‐c‐9,10‐epoxy‐7,8,9,10‐tetrahydro‐B[a]P (DE1) formed from (–)‐7,8‐diol was significantly increased by the introduction of anionic lipids, but not by that of nonbilayer lipids. Thus, charged lipids affect the stereoselectivity of the epoxidation by leading to the formation of a larger amount of the ultimate mutagen DE2 than of DE1, which is far less carcinogenic. These data suggest that membrane properties such as negative charge and nonbilayer phase propensity are important for the efficiency and selectivity of enzymatic function of human CYP1A1.
Functionally active fusion protein of the novel composite cytokine CLC/soluble CNTF receptor
Authors: Guillet Catherine , Lelièvre Eric , Plun‐Favreau Hélène , Froger Josy , Chabbert Marie , Hermann Jacques , Benoit de Coignac Amelie , Bonnefoy Jean‐Yves , Gascan Hugues , Gauchat Jean‐François , Elson Greg
Published: October 2003

The heterodimeric cytokine composed of the soluble ciliary neurotrophic factor receptor (sCNTFR) and the IL‐6 family member cardiotrophin‐like cytokine (CLC) was recently identified as a new ligand for gp130–leukemia inhibitory factor receptor (LIFR) complex [Plun‐Favreau, H., Elson, G., Chabbert, M., Froger, J., deLapeyriere, O., Lelievre, E., Guillet, C., Hermann, J., Gauchat, J. F., Gascan, H. & Chevalier, S. (2001) EMBO J.20, 1692–1703]. This heterodimer shows overlapping biological properties with LIF. Although CLC contains a putative signal peptide and therefore should enter into the classical secretory pathway, the protein has been shown to be retained within transfected mammalian cells, unless coexpressed with either sCNTFR or cytokine like factor (CLF) [Elson, G. C., Lelievre, E., Guillet, C., Chevalier, S., Plun‐Favreau, H., Froger, J., Suard, I., de Coignac, A. B., Delneste, Y., Bonnefoy, J. Y., Gauchat, J. F. & Gascan, H. (2000) Nat. Neurosci.3, 867–872]. In the present study, we demonstrate that a fusion protein comprising CLC covalently coupled through a glycine/serine linker to sCNTFR (CC–FP) is efficiently secreted from transfected mammalian cells. CC–FP shows enhanced activities in respect to the CLC/sCNTFR native complex, on a number of cells expressing gp130 and LIFR on their surface. In addition, CC–FP is able to compete with CNTF for cell binding, indicating that both cytokines share binding epitope(s) expressed by their receptor complex. Analysis of the downstream signaling events revealed the recruitment by CC–FP of the signal transducer and activator of transcription (STAT)‐3, Akt and mitogen‐activated protein (MAP) kinase pathways. The monomeric bioactive CLC/sCNTFR fusion protein is therefore a powerful tool to study the biological role of the recently described cytokine CLC.
Development of species‐specific PCR primers on rDNA for the identification of European Armillaria species
Authors: Sicoli G. , Fatehi J. , Stenlid J.
Published: October 2003

Attempts to design species‐specific PCR primers from six European Armillaria species in the ribosomal RNA genes are reported. Primers were developed on the basis of the nucleotide sequence variability of the internal transcribed spacers (ITS) and the intergenic spacer (IGS1) of the ribosomal DNA. Four sets of primers gave specific PCR products for Armillaria tabescens, Armillaria mellea and Armillaria ostoyae. However, due to the high sequence similarities between Armillaria borealis and Armillaria ostoyae and between Armillaria cepistipes and Armillaria gallica no species specific amplification was obtained for these taxa.
Responses of conifer species of the Great Lakes region of North America to inoculation with the pitch canker pathogen Fusarium circinatum
Authors: Enebak S. A. , Stanosz G. R.
Published: October 2003

Five conifer species grown in the Great Lakes region of North America were examined for their susceptibility to Fusarium circinatum, (syns. Fusarium subglutinans f. sp. pini and F. moniliforme var. subglutinans), the causal agent of pitch canker. Three‐year‐old (3‐0) seedlings of red (Pinus resinosa), jack (P. banksiana) eastern white (P. strobus), Scots (P. sylvestris) and Austrian (P. nigra) pine were planted in 4 l pots in a greenhouse at Auburn University in November 1998. In April and June 1999, seedlings were inoculated by removing a needle fascicle approximately 5 cm from the terminal bud and placing a drop containing F. circinatum conidia on the wound. Resin production, canker length and seedling mortality were recorded 12 weeks later. Jack, Scots and eastern white pine were the most susceptible with Austrian and red pine more resistant to the fungus. F. circinatum was re‐isolated from 37% to 96% of inoculated seedlings. The susceptibility of jack, Scots and eastern white pine indicates a potential risk to these important species of the region if F. circinatum were to be introduced into the area.
Factors Consumers Identify as Important to Recovery from Schizophrenia
Authors: Tooth Barbara , Kalyanasundaram Vaidyanathan , Glover Helen , Momenzadah Sirous
Published: October 2003

Objective: The purpose of the present study was to provide a consumer perspective on recovery from schizophrenia and to identify what consumers considered important in this journey, compare it to the literature and also to provide a consumer definition of recovery.

Methods: A four-part qualitative process was developed following consultation with two consumer focus groups. Fifty-seven people who identified themselves as in recovery participated in the study. The interviews were tape-recorded and thematic analysis used to identify the common themes used by the participants.

Results: The most frequently reported category related to an active sense of self, with the person's determination to get better, manage their illness and realising their need to help themselves the most common subcategories.

Conclusions: The findings of the present study are discussed in relation to the literature on recovery from mental illness and their implications for the provision of services.
Lack of microsatellite instability in neoplasms of ampulla of Vater
Authors: Park Sunhoo , Kim Sun Whe , Kim Sun Hee , Darwish Nevine S. , Kim Woo Ho
Published: October 2003

To clarify the genetic background of ampullary neoplasm, we investigated the occurrence of microsatellite instability (MSI) in 64 samples of neoplasm of the ampulla of Vater. Eight out of 22 adenomas (34.6%), nine out of 32 carcinomas (28.1%) and one metastatic lesion (10.0%) showed MSI in 1–3 of the nine dinucleotide markers; those cases are categorized into microsatellite instability‐low (MSI‐L). The remaining samples were stable with respect to all of the tested markers. None of the samples showed a frameshift mutation in the poly A‐tract of BAT‐26 or transforming growth factor‐β type II receptor, which are frequently mutated in gastric or colorectal cancers showing microsatellite instability. To confirm our finding, we stained 93 ampullary neoplasms with antibodies against the mismatch repair proteins: hMLH1 and hMSH2. All tumors were found to express mismatch repair proteins. In contrast to gastric or colorectal cancers, MSI does not play an important role in the carcinogenesis of ampullary carcinoma.
Primary carcinoid tumor of the testis: Immunohistochemical, ultrastructural and FISH analysis with review of the literature
Authors: Kato Noriko , Motoyama Teiichi , Kameda Noriaki , Hiruta Nobuaki , Emura Iwao , Hasegawa Go , Murata Tetsuya , Kimura Mikihiko , Tsuda Hitoshi , Ishihara Tokuhiro
Published: October 2003

Primary carcinoid tumor of the testis only accounts for 0.2% of all carcinoid tumors in Japan. The clinicopathological features, including differences between Japanese and Europe/United States (Eur/US) series’, which are known in ovarian carcinoids, have not yet been sufficiently recognized. In the present study, five testicular carcinoids from various clinicopathological viewpoints were analyzed, with a review of the literature. All 15 cases in Japan, including 10 previously reported, were insular carcinoids. Three of the 15 cases (20%) were associated with a teratoma. Serotonin production was confirmed in at least 10 cases (five cases in the present study and five cases in previous studies), but carcinoid syndrome was present in only two cases. Three of the 15 cases (20%) showed distant metastases, and the tumors that metastasized were larger than those that did not. These features were almost similar to those observed in the Eur/US series. Three pure carcinoids were also studied for the number of sex chromosomes by fluorescence in situ hybridization (FISH). They did not show a significant numerical abnormality of the X chromosome, which is common in testicular germ cell tumors. Therefore, the genetic background of pure carcinoids might be different from that of common germ cell tumors.
Dedifferentiated malignant myoepithelioma of the parotid gland
Authors: Ogawa Ikuko , Nishida Toshihiro , Miyauchi Mutsumi , Sato Sunao , Takata Takashi
Published: October 2003

Dedifferentiated salivary gland tumor is a rare, recently recognized tumor type. A case of dedifferentiated malignant myoepithelioma in a 59‐year‐old man who presented with a painful mass in the left preauricular region is reported. Histologically, two distinct neoplastic cell populations were observed in the same tumor mass. The first population was composed of solid nests of polygonal eosinophilic or glycogen‐rich clear cells showing neoplastic myoepithelial immunocytological features, such as positivity for cytokeratins, vimentin, S‐100 protein (S‐100), α‐smooth muscle actin (SMA) and glial fibrillary acidic protein (GFAP). A multinodular growth pattern, necrosis and occasional mitotic figures suggested malignancy. This population was diagnosed as low‐grade malignant myoepithelioma. The second population infiltrated diffusely into the parotid gland and facial nerves. It consisted of polygonal or short spindle cells with obvious pleomorphism and atypical mitoses. The tumor cells were positive for vimentin and cytokeratins, and showed an accumulation of p53 and cyclin D1. S‐100 protein, SMA and GFAP were negative. This population was regarded as undifferentiated carcinoma. A final diagnosis of dedifferentiated malignant myoepithelioma was made. This seems to be the first published case of dedifferentiation in malignant myoepithelioma. Because any tumor type can undergo dedifferentiation with accumulation of additional genetic changes, complete sampling should be the standard approach to all salivary gland tumors in order to avoid missing a dedifferentiation component.
Microwave cell death: Immunohistochemical and enzyme histochemical evaluation
Authors: Ozaki Takashi , Mori Ichiro , Nakamura Misa , Utsunomiya Hirotoshi , Tabuse Katsuyoshi , Kakudo Kennichi
Published: October 2003

In Japan, microwave coagulation therapy (MCT) has been used for the management of primary and metastatic liver cancer. Needle biopsy examination from the lesion has frequently shown the presence of nucleated cancer cells in histopathological examinations, prompting the conclusion that cancer cells are not completely eliminated by microwave therapy, whereas computed tomography and ultrasonography examinations show tumor regression. To determine whether microwave‐treated tissue contains functionally viable cells, an examination of the Na+‐K+‐ATPase protein and its activity using immunohistochemical and enzyme histochemical methods were carried out in microwave‐treated rat liver. Four concentric, morphologically identifiable zones around the microwave probe needle appeared 2 days after treatment. Zone A, which was between the innermost spongy zone and the outer necrotic zone, contained only slight morphological alterations in the hepatocytes, which had slightly hyperchromatic nuclei and mildly eosinophilic cytoplasm. The hepatocytes in zone A were found to be positive for the Na+‐K+‐ATPase antigenicity but negative for enzyme activity, indicating that zone A was undergoing cell death, although morphologically this was not discernible. This type of cell death caused by microwave treatment is morphologically different from previously known types of cell death, either oncosis or apoptosis.
Cholesterol hepatolithiasis with peribiliary cysts
Authors: Terada Tadashi , Matsushita Hiroshi , Tashiro Jo , Sairenji Takayuki , Eriguchi Masazumi , Osada Isao
Published: October 2003

A 78‐year‐old man was admitted to our clinic because of fatigue. Imaging modalities showed beaded stricture and dilation of the intrahepatic left segmental bile duct. Anomalous pancreatico‐biliary ductal union and polycystic kidney disease were absent. Resection of the hepatic left lobe was performed. Grossly, cholesterol stones were impacted in  the  dilated  intrahepatic  large  bile  ducts,  and  multiple tiny cysts measuring 2–8 mm were noted in the peribiliary areas (peribiliary cysts). Histologically, the cholesterol hepatoliths consisted of cholesterol empty spaces and fibrinous materials, and, in places, foreign body giant cells were seen around the cholesterol crystals. The peribiliary cysts were lined by a layer of cuboidal epithelia. They were intimately intermingled with intrahepatic peribiliary glands, and a close association between the two components was recognized in some places. A mild degree of ascending cholangitis was noted. Bile duct anomalies including von‐Meyenburg complexes and simple cysts were not recognized. Peribiliary cysts have been reported in various liver diseases, including portal hypertension, portal thrombosis, cirrhosis, hepatocellular carcinoma, and adult polycystic kidney disease. However, to the best of our knowledge, there have been no reports on peribiliary cysts developing in hepatolithiasis. The present case indicates that peribiliary cysts occur in cholesterol hepatolithiasis, and suggests that they are derived from cystic dilations of intrahepatic peribiliary glands.
Cardiac ankyrin repeat protein is preferentially induced in atrophic myofibers of congenital myopathy and spinal muscular atrophy
Authors: Nakada Chisato , Oka Akira , Nonaka Ikuya , Sato Kenzo , Mori Shigeo , Ito Hisao , Moriyama Masatsugu
Published: October 2003

Cardiac ankyrin repeat protein (CARP), which is structurally characterized by the presence of four ankyrin repeat motifs in its central region, is believed to be localized in the nucleus and to participate in the regulation of cardiac‐specific gene expression in cardiomyocytes. However, we recently found that CARP was induced in skeletal muscle by denervation, leading us to speculate that CARP may be induced under some pathological conditions. In the present study, we immunohistochemically analyzed the expression of CARP in 11 cases of spinal muscular atrophy (SMA) and 14 cases of congenital myopathy. In SMA, CARP was expressed selectively in severely atrophic myofibers, suggesting that CARP expression may reflect the status of muscle atrophy. Furthermore, in the congenital myopathies, the expression patterns of CARP were distinct among the subtypes, which included nemaline myopathy, myotubular myopathy, central core disease, and congenital fiber type disproportion. Although CARP was preferentially expressed in severely damaged myofibers in nemaline myopathy, it was not detected in central core disease. These findings suggest that immunohistochemical evaluation of CARP may be helpful in the diagnosis of SMA and the congenital myopathies.
Histological study of fetal kidney with urethral obstruction and vesicoureteral reflux: A consideration on the etiology of congenital reflux nephropathy
Authors: SHIMADA KENJI , MATSUMOTO FUMI , TOHDA AKIRA , UEDA MASANAO
Published: October 2003

Purpose: A recent subject of interest regarding reflux nephropathy is the presence of renal abnormalities in neonates and infants who have no history of urinary tract infections. Debates have centered on the etiology of this renal abnormality – congenital reflux nephropathy; regarding whether it is the result of abnormal ureteral budding or of back pressure effect from sterile reflux. We examined the renal pathology of fetuses with urethral obstruction and vesicoureteral reflux, and we suggest herein a possible etiology of congenital reflux nephropathy.

Methods: The renal pathology of seven autopsied fetuses with vesicoureteral reflux was studied. Reflux was demonstrated at autopsy by slow injection of contrast medium into the bladder. Severe urethral obstruction, either atresia or urethral valves, was evident in six of the subjects.

Results: In six subjects, abnormality of the urinary tracts was detected by prenatal ultrasonography. Of these six subjects, three revealed characteristics of prune belly syndrome. Reflux was graded as moderate in five subjects, and severe in two. In three subjects autopsied at 21 weeks gestation or earlier, the kidneys were well‐developed with normal corticomedullary configuration, and nephrogenesis was retained. In three cases autopsied at over 25 weeks of gestation, the kidneys were grossly cystic, and the nephrogenic zone was completely absent. Contrast medium was observed not only in the dilated ducts and tubules, but also in the subcapsular cysts. Extravasation of the contrast medium was seen in the peritubular space. In the last subject with normal lower urinary tract, abnormal segments among normal cortical structures were observed.

Conclusion: Our findings of renal pathology in fetuses with reflux are quite similar to those seen in fetal hydronephrosis. Back pressure from reflux probably damages the developing kidney leading to a degeneration of the ampullae and a reduction in the number of nephrons. Both dilatation of the collecting ducts and tubules, and extravasation of the urine may result in interstitial fibrosis. We postulate that one of the important etiologies of congenital reflux nephropathy may be the result of back pressure from sterile reflux.
Spontaneous disappearance of a renal arteriovenous malformation
Authors: KUBOTA HIROKI , SAKAGAMI HIROSHI , Kubota YASUE , SASAKI SHOICHI , UMEMOTO YUKIHIRO , KOHRI KENJIRO
Published: October 2003

Abstract We describe herein a case of complete spontaneous disappearance of a congenital arteriovenous malformation (AVM). A 28‐year‐old male was hospitalized for right flank pain and gross hematuria, followed by bladder tamponade. To improve the patient's symptoms, bladder irrigation was performed. Cystoscopy demonstrated bloody urine from the right ureteral orifice. Right selective renal arteriography demonstrated tortuous, coiled vascular channels with early filling of the renal vein. Thus, right renal AVM was diagnosed. However, the patient refused further treatment and was discharged. One year later, massive hematuria recurred with bladder tamponade and the patient was rehospitalized. Renal arteriography did not show any evidence of AVM and there has been no hematuria since.
Analysis of serum α‐fetoprotein concentration in patients with viral hepatitis
Authors: SHE Wei Min , HU De Chang , YUAN He Jun , ZHAI Wei Rong , LIANG Yi , LIU Hou Yu
Published: October 2003

OBJECTIVE: To investigate serum α‐fetoprotein (AFP) concentrations in patients with viral hepatitis.

METHODS: Serum concentrations of total bilirubin (TB), alanine aminotransferase (ALT), aspartate amino­transferase (AST), albumin, globulin, AFP and viral markers were determined in 310 patients with pathologically proven viral hepatitis. The relation between the concentration of AFP and clinical manifestation, pathology, family history of liver malignant disease and virus type was studied.

RESULTS: Serum AFP concentrations were elevated in 115 of the 310 patients (37.1%). According to the pathological diagnosis, the lowest positive rate of AFP was in acute hepatitis (11.7%), the highest was in chronic severe hepatitis (66.7%), the second highest in liver cirrhosis (57.5%), and chronic hepatitis was intermediate (34.2%). If the diagnosis was based on the clinical manifestation, the highest positive rate was found in chronic severe hepatitis, the lowest in chronic hepatitis, and acute hepatitis was intermediate. The positive rate of serum AFP by virus type was 35.5% for hepatitis B (HBV), superinfected with HAV or with HEV was 62.8%, and with HCV was 27.3%. Only one in six patients with HCV infection and none with simple HAV or HEV infection were positive for AFP. In patients with a family history of liver cancer, the positive rate of AFP was higher than in those without such a history (57.9%vs38.2%;P = 0.75).

CONCLUSIONS: The results indicate that AFP positivity is not uncommon in patients with viral hepatitis and if the patient has an elevated concentration, it is highly likely to be HBV infection or HBV super­infected with HAV or HEV.
Survey of the genotype for S‐mephenytoin hydroxylase in the Chinese Han population
Authors: WANG Hong , LI Yu Yuan , NIE Yu Qiang , WANG Han Ping , MAO Ping , XIE Jian Jin
Published: October 2003

OBJECTIVE:  S‐mephenytoin hydroxylase is a polymorphic cytochrome P450 (CYP) enzyme that catalyzes the metabolism of omeprazole, a proton‐pump inhibitor, and some other drugs. The aim of this survey was to investigate the distribution of the genotype of S‐mephenytoin hydroxylase in Chinese people.

METHODS:  One hundred and fifty‐five unrelated healthy volunteers were selected and their blood samples were used for genotyping by PCR‐restriction enzyme analysis. DNA from homozygous extensive metabolizers (EM) could be digested into two fragments, whereas poor metabolizers (PM) could not be digested and heterozygous EM could be partly digested.

RESULTS:  Two mutations of CYP2C19 were found; that is, m1 and m2. The frequency of the PM (m/m) genotype was 15.5% (24/155) and that of EM was 84.5% (131/155). The EM included 36.8% (57/155) homo‐EM (wt/wt) and 47.7% (74/155) hetero‐EM (wt/m).

CONCLUSIONS:  There were two forms of CYP2C19 mutations. The frequency of PM (m/m) and heterozygous EM genotype (w/m) in Chinese people were significantly higher than those of Western white people. Hetero‐EM were more common than homo‐EM in the Chinese population. The genotyping variation might explain the different effect of PPI on individuals.
Is cranberry juice effective in the treatment and prevention of Helicobacter pylori infection of mice?
Authors: XIAO Shu Dong , SHI Tong
Published: October 2003

OBJECTIVE:  It is well known that eradication of Helicobacter pylori infection results in healing of peptic ulcer and regression of gastric mucosal inflammation. Cranberry juice beverages have been shown to achieve good results in the prevention of recurrent urinary tract infection. The present study aimed to investigate whether a cranberry juice cocktail could eradicate or prevent H. pylori infection in mice.

METHODS:  In the therapeutic trial, C57BL/6 mice were infected with H. pylori and 2 weeks later, 80 mice were randomly allocated into four groups: Group A, cranberry juice (0.5 mL/mouse, p.o. daily for 30 days); Group B, triple therapy (amoxycillin 50 mg/kg, bismuth subcitrate 6.15 mg/kg, and metronidazole 22.5 mg/kg, daily for 14 days); Group C, a combination of cranberry juice and triple therapy; Control Group, the mice were infected with H. pylori and left untreated. The mice were killed after 24 h and 4 weeks and H. pylori infection status was assessed by rapid urease test and by culture and histology, respectively. In the prevention trial, 40 mice had oral cranberry juice for 30 days. In the last 5 days (days 26−30), the mice were divided into four groups: Group A, challenged orally with H. pylori three times on days 26, 28 and 30 when the mice were not given cranberry juice; Group B, challenged with H. pylori suspended in cranberry juice; Group C, challenged with H. pylori 6 h after receiving juice; Control group, no cranberry juice, but challenged with H. pylori. Two weeks later, the mice were killed to assess the status of H. pylori infection.

RESULTS:  The clearance rates at 24 h after treatment in groups A, B and C were 80%, 100%, and 90%, respectively (P < 0.01 as compared with Control group, two tailed Fisher's Exact Probability Test). Four weeks after cessation of treatment the eradication rates in groups A, B and C were 20% (P = 0.474, two tailed Fisher's Exact Probability Test), 80% and 80%, respectively (P < 0.01). None of the mice were clear of H. pylori infection.

CONCLUSIONS:  Cranberry juice can clear H. pylori infection in mice with a clearance rate of 80%, but the eradication rate was low (20%). Cranberry juice was not effective in preventing H. pylori infection in the mice used in this study.
Saquinavir induces stable and functional expression of the multidrug transporter P‐glycoprotein in human CD4 T‐lymphoblastoid CEMrev cells
Authors: Dupuis ML , Flego M , Molinari A , Cianfriglia M
Published: October 2003

Background

The multidrug transporter P‐glycoprotein (P‐gp) is expressed in HIV‐1 target cells, in a range of pharmacological barriers and in AIDS‐associated tumours. P‐gp substrates include HIV‐1 protease inhibitors (PIs) and anticancer drugs, which are efficiently effluxed from multidrug‐resistant (MDR) cells.

Objectives

The aim of this study was to investigate the effect on human CD4 T‐lymphoblastoid CEMrev cells of saquinavir and other PIs in terms of P‐gp expression and to characterize the functional and biochemical patterns of PI‐induced P‐gp molecules.

Methods

CEMrev cells no longer expressing detectable amounts of P‐gp were cultured for a prolonged period in the presence of 10 μg/mL saquinavir (CEMsaq10) and tested for P‐gp expression and function. Subsequently, CEMsaq10 cells were transferred into medium containing 15 μg/mL saquinavir (CEMsaq15) and cultured for several months. These cell lines were continuously monitored for P‐gp expression, function and immunochemical patterns. A similar strategy was adopted to determine whether other PIs, such as ritonavir and indinavir, were able to induce P‐gp expression in CEMrev cells.

Results

Compared with the drug‐diluent control, the exposure of CEMrev cells to 10μg/mL saquinavir induced, in a consistent fraction of cells (45–50%), de novo expression of functioning P‐gp molecules. The transfer of CEMsaq10 cells to 15μg/mL saquinavir was associated with a dramatic increase in P‐gp expression and function (85–90% of CEMsaq15 cells expressed P‐gp and effluxed P‐gp dye substrates). These saquinavir‐induced P‐gp molecules included 75‐kDa molecules as well as the classical 170‐kDa form of P‐gp, suggesting induction of a particular isoform of P‐gp termed mini‐P‐glycoprotein. Conversely, ritonavir and indinavir induced transient P‐gp expression in a small percentage of the CEMrev cells.

Conclusions

Treatment of human CD4 T‐lymphoblastoid CEMrev cells with saquinavir caused over‐expression of functioning P‐gp molecules. This de novo acquired MDR phenotype, which differed from that induced by other PIs, was stable, as expression and activity of P‐gp were observed in CEMsaq10 and CEMsaq15 cells during prolonged in vitro culturing, even in drug‐free conditions.
Laser Doppler Velocimetry and Flow Visualization Studies in the Regurgitant Leakage Flow Region of Three Mechanical Mitral Valves
Authors: Meyer Richard S. , Deutsch Steven , Bachmann Christopher B. , Tarbell John M.
Published: October 2003

Abstract: Streak line flow visualization and laser Doppler velocimetry (LDV) were conducted in the regurgitant leakage flow region of 3 mechanical heart valve types: CarboMedics, Medtronic Hall, and St. Jude Medical. Streak line flow visualization identified regions of high regurgitant flow, and LDV measurements were focused on those locations. Maximum regurgitant flow velocities after valve closure ranged from 0.7 to 2.6 m/s, and maximum Reynolds shear stress after valve closure ranged from 450 to 3,600 dyne/cm2. These data indicate that leakage flows can generate turbulent jets with elevated Reynolds stresses even in bileaflet valves.
Coronary Artery Bypass Grafting for Hemodialysis‐ Dependent Patients
Authors: Hirose Hitoshi , Amano Atushi , Takahashi Akihito , Ozaki Shigeyuki , Nagano Naoko
Published: October 2003

Abstract:Patients with end‐stage renal disease carry a risk of coronary atherosclerosis. This study was performed to evaluate the perioperative and remote data of coronary artery bypass grafting (CABG) in hemodialysis dependent patients. We retrospectively analyzed the results of isolated CABG performed at Shin‐Tokyo Hospital between June 1, 1993 and May 31, 2000. Preoperative, perioperative, and follow‐up data of the patients on hemodialysis (Group HD, n = 37) were collected and compared with those of control patients (Group C, n = 1,639). Group HD consisted of 26 males and 11 females with a mean age of 59.9 ± 8.1 years, and the mean number of bypasses was 2.5 ± 1.1. Group HD had a longer postoperative intubation time, ICU stay, and hospital stay than Group C. The postoperative major complication rate in Group HD (18.9%) was not significantly different from that in Group C (11.3%). However, the inhospital mortality rate in Group HD (5.4%) was higher than Group C (0.6%). At the mean follow‐up of 2.4 years, the actuarial 3‐year survival of Groups HD and C were 90.6% and 97.6%, respectively (p < 0.001), excluding hospital mortality. The actuarial 3‐year cardiac event‐free rates were 84.3% in Group HD and 88.8% in Group C, showing no difference. Patients on chronic hemodialysis carry a significant risk of prolonged inhospital care and hospital death. Once successful surgical revascularization was completed, their long‐term cardiac events could be controlled as effectively. The increased distant death rates was probably associated with the nature of renal disease.