bluuebunny/crossref_metadata_2025 huggingface dataset:
Antiproliferative effects of heparin on normal and transformed NIH/3T3 fibroblasts.
Authors: Cavari Simone , Ruggiero Marco , Vannucchi Simonetta
Published: October 2002

We studied the effect of heparin on proliferation and signalling in normal NIH/3T3 fibroblasts, and in cells transformed by different oncogenes. Heparin inhibited the proliferation of normal as well as of v‐sis and v‐erbB transformed fibroblasts in the presence of serum, but failed to inhibit v‐erbB‐driven proliferation in serum‐starved cultures; under these conditions, heparin inhibited by approximately 50% the proliferation of normal and v‐sis‐ transformed cells. Heparin also inhibited PDGF‐induced cell proliferation and inositol lipid turnover in v‐sis transformants, but it did not affect PDGF mitogenic signalling in NIH/3T3 fibroblasts.
An elastinolytic enzyme detected in the culture medium of human arterial smooth muscle cells
Authors: Okada Yoshikatsu , Katsuda Shogo , Okada Yasunori , Nakanishi Isao
Published: October 2002

The culture medium of human arterial smooth muscle cells exhibits an elastinolytic activity with 68 and 64 kDa on elastin substrate gels. The enzymatic activities are inhibited by ethylenediamine tetraacetic acid, a metalloproteinase inhibitor, but not by other inhibitors of serine, cysteine and aspartic proteinases. The proteinase in the culture medium is activatable by 4‐aminophenylmercuric acetate and degrades insoluble elastin. Compared to other matrix metalloproteinases (MMP), the activity shows the similar elastinolytic pattern to that by MMP‐2 purified from human rheumatoid synovium, while MMP‐3 and MMP‐9 have different lytic patterns and MMP‐1 possesses no elastinolytic activity. An immunoblot analysis demonstrated that the 68‐kDa enzyme is MMP‐2. An immunofluorescence study illustrates that MMP‐2 is localized within the cytoplasm of the smooth muscle cells. These findings suggest that the elastinolytic enzyme secreted by human arterial smooth muscle cells is MMP‐2.
Exogenous catalase introduced in CHO cells by electroporation does not protect against chromosome damage induced by ionizing radiation.
Authors: Cortés Felipe , Domínguez Inmaculada , Sandström Björn
Published: October 2002

The relative importance of hydrogen peroxide generated as a consequence of irradiation with X‐rays for the production of chromosomal aberrations has been studied in cultured CHO cells. Catalase introduced into cells by electroporation protected DNA from strand breakage induced by hydrogen peroxide given 4h later, and the yield of chromosome aberrations was also reduced. Nevertheless, when the cells were irradiated after treatment with catalase following a similar protocol and the yield of chromosomal aberrations analyzed at metaphase, no protective effect was observed as compared with cells treated with X‐rays alone. These observations seem to support the hypothesis that hydroxyl radicals generated from hydrogen peroxide are not a major factor responsible for chromosome damage induced by ionizing radiation.
Elongation factor 1α is a component of the subcortical actin bundles of characean algae.
Authors: Collings David A. , Wasteneys Geoffrey O. , Miyazaki Masazumi , Williamson Richard E.
Published: October 2002

Antibodies to elongation factor 1α (EF1α), a known 50 kDa actin‐bundling protein in Dictyostelium, identified a protein in a whole cell extract of the characean alga Nitella pseudoflabellata that had an apparent molecular weight of 51 kDa. Indirect immunofluorescence microscopy revealed labelling by the EF1α antibodies of the subcortical actin bundles, even after the motile organelles of the endoplasm were removed by perfusion with ATP‐containing solutions.
Field bean protease inhibitor preparations, unlike methotrexate, can completely suppress Yoshida sarcoma tumor in rats
Authors: Banerji Ashutosh P. , Fernandes Augustine O.
Published: October 2002

Protease inhibitor preparations (PIP) with antitryptic and antichymotryptic activities, isolated from field bean legume as well as doxorubicin and cyclophosphamide could effectively suppress the growth of Yoshida sarcoma ascites tumor cells transplanted in adult rats and prevent their death. As against this, methotrexate and heat‐inactivated PIP were ineffective in such rats at varied doses of treatment tried. The percent survival of animals appeared to be related to the purity, treatment mode and the dose of PIP used. Zymographic analysis of the trypsin activated sarcoma cell homagenate revealed the presence of six protease bands in the molecular weight range of 51kD to 206kD. Prolonged interactions of such zymograms with protease inhibitors such as 20mM EDTA or 5mM diisopropyl fluorophosphate (DIFP) or 400 · μg/ml of PIP in reaction buffer indicated that these are not metalloproteases but serine proteases whose activities are inhibited by PIP and DIFP. Since proteases are involved in cell growth regulation and cell transformation, we hypothesize a positive relationship between the field bean protease inhibitor;s blocking action on tumor cell proteases and its tumor suppressing activity
Tumor necrosis factor alpha, a cytokine coregulating sugar uptake by cultured human synovial cells.
Authors: Hernvann Alain , Souliac‐Marc Catherine , Aussel Christian , Ekindjian Ohvanesse
Published: October 2002

Confluent cultures of osteoarthritic and rheumatoid human synovial cells were treated with human recombinant tumor necrosis factor alpha (TNF‐α) The cytokine increased uptake of 2‐deoxy‐D‐[1‐3H]glucose (2‐DOG) in a time‐ and concentrations‐dependent manner. In synovial cells obtained from osteoarthritic patients (OA cells), the stimulation of 2‐DOG uptake occurred 3 hours following addition of TNF‐α (1 ng/ml) and was maximal by 24 hours Rheumatoid synovial cells (RA cells) appeared less sensitive to the cytokine: 2‐DOG uptake stimulation was only significant after 6 hours of incubation. In both OA and RA cells, the effect was protein synthesis‐dependent, and was not secondary to prostaglandin E2 synthesis or cell growth. Interteukin‐1β was more efficient than TNF‐α for 2‐DOG uptake stimulation The two cytokines seemed to act in an additive manner.
Cytotoxicity of vacuolar H+ ‐ATPase inhibitors to UMR‐106 rat osteoblasts: an effect on iron uptake into cells?
Authors: Hall Tony J.
Published: October 2002

Treatment of rat osteoblastic UMR‐106 cells with bafilomycin A1 rhamnoside or concanamycin A, which are potent and specific inhibitors of the vacuolar H+‐ATPase (V‐ATPase), caused a rapid rounding up of the cells (within 6 hr), inhibition of cell growth (IC50 = 3.3 nM and 0.5 nM, respectively, at 24 hr) and cell death at 54 hr. Since proliferating cells have an absolute requirement for iron and the V‐ATPase plays a crucial role in iron uptake into cells via the transferrin cycle, the effect of the iron chelator, desferal, was tested on UMR‐106 cells. A time‐dependent cell rounding, suppression of cell growth followed by cell death very similar to that observed with the V‐ATPase inhibitors was seen. Therefore, the in vitro and in vivo toxicity of V‐ATPase inhibitors may be due, at least in part, to their preventing iron uptake into cells.
The effect of cisplatin and transplatin on the conformation and association of F‐actin.
Authors: Hui Zeng Hui , Fen Lu Jing , Kui Wang
Published: October 2002

The effects of cisplatin and transplatin on the conformation and association of F‐actin were studied by ESR, turbidimetry and CD measurement. The results indicate that the major component affecting F‐actin secondary conformation is derived from their effect on the tertiary or quaternary conformation and association states of F‐actin. The effect of platinum is seen by the fact that binding of cisplatin causes first an increase in molecular size followed by a later decrease. The induction time for the association depended on the concentration of cisplatin. Transplatin was able to reach the target site more readily, resulting in the dissociation of F‐actin even at a very low concentration.
WHERE AM I? HOW A CELL RECOGNIZES ITS POSITIONAL INFORMATION DURING MORPHOGENESIS
Authors: HATA RYU‐ICHIRO
Published: October 2002

Morphogenesis is an old, and one of the latest, fascinating fields in biological science and a huge number of papers on molecular mechanisms underlying it have been published. But most of the works and reviews on these mechanisms pertain to molecules of, as it were, the planning or design of morphogenesis, such as morphogens and homeodomain proteins. In this review, I will describe the function of extracellular matrix (ECM) and other cell adhesion molecules in morphogenesis as that of actual morpho‐creating molecules, morphocreators, and discuss their roles as positional information‐pertaining molecules.
CELL DEATH, SURVIVAL AND PROLIFERATION IN TETRAHYMENA THERMOPHILA. EFFECTS OF INSULIN, SODIUM NITROPRUSSIDE, 8‐BROMO CYCLIC GMP, NG‐METHYL‐L‐ARGININE AND METHYLENE BLUE
Authors: CHRISTENSEN SØREN T. , KEMP KÅRE , QUIE HELENE , RASMUSSEN LEIF
Published: October 2002

Cells of the ciliate Tetrahymena thermophila produce compounds that act as autocrine (paracrine) survival and/or growth factors. 8‐Bromo cyclic GMP, sodium nitroprusside, hemin, protoporphyrin IX, human recombinant and bovine insulin were tested for their ability to substitute for the cell‐produced factors and stimulate cell survival and proliferation. The cells were inoculated into conical flasks in a nutritionally complete, chemically defined medium at known cell densities from 5 to 5000cells/ml. In unsupplemented medium cells at 5 to 500cells/ml (‘low initial cell density cultures’) died within 8h, whereas cells at 1000 and 5000cells/ml (‘high initial cell density cultures’) proliferated with lag phases lasting for up to 4h. In the presence of insulin compounds, hemin, protoporphyrin IX, or 8‐bromo cyclic GMP, cells also proliferated at all low initial cell densities. Sodium nitroprusside was effective over two separate concentration ranges: at the nanomolar levels as well at low pico‐ to femtomolar levels. At initial population densities of up to 50cells/ml the cells at both concentrations of sodium nitroprusside survived about 4‐fold longer than the controls. At 500 initial cells/ml, cells at thehigh concentrations of sodium nitroprusside survived about 4‐fold longer than those of the control cultures; they proliferated in the low concentrations of sodium nitroprusside. Concentrations of hemin, too low to have any effects on their own, had synergistic effects with sodium nitroprusside. NG‐methyl‐L‐arginine inhibited proliferation at high initial cell densities. This inhibitory action was reduced by high concentrations of L‐arginine, protoporphyrin IX, sodium nitroprusside, or 8‐bromo cGMP, but not by insulin. Methylene blue inhibited cell proliferation at high initial cell densities. This inhibition was circumvented by addition of 8‐bromo cGMP. The findings that insulin‐related material may be released from Tetrahymena and that insulin and sodium nitroprusside increase intracellular cGMP in these cells are discussed in relation to the presented results. Together these observations suggest that cGMP is responsible for supporting cell survival in Tetrahymena and switching the cells into their proliferative mode, and that cell‐produced signal molecules and insulin stimulate an NO‐dependent guanylate cyclase into producing cGMP.
A FINE STRUCTURAL STUDY OF THE HIPPOCAMPUS AND DORSAL ROOT GANGLION IN MOUSE TRISOMY 16, A MODEL OF DOWN'S SYNDROME
Authors: LANE NANCY J. , BALBO ANDREA , RAPOPORT STANLEY I.
Published: October 2002

Mouse trisomy 16 (Ts16) appears to provide an animal model of Down's syndrome in that a portion of mouse chromosome 16 is syntenic with part of human chromosome 21. Trisomy 21 in human beings leads to the mental retardation of Down's syndrome and in middle age, to some presenile anatomic and clinical features of Alzheimer's disease. Neural tissue from aging Ts16 mice is unavailable, however, as Ts16 mouse embryos die late in utero. We studied these embryos looking at the ultrastructure of neurons from the hippocampus and dorsal root ganglion in normal control mice embryos (diploid) and in Ts16 late embryonic litter mates after day 15 of gestation. The organelles in the Ts16 neurons looked similar to those in control neurons, fixed and processed under similar conditions. No obvious neuropathological structures were observed. These results, when compared to reports on electrophysiological abnormalities of cultured fetal Ts16 neurons and on abnormalities in neurotransmitter markers in the Ts16 fetal brain, lead us to suggest that the mental retardation of Down's syndrome is likely to result from functional and chemical defects not directly related to abnormal neuronal ultrastructure. When related to fine structural studies of transplanted embryonic Ts16 hippocampus which have been maintained for long periods of time, these results indicate that the trisomic mouse brain would not be useful as a structural model for Down's syndrome and hence presenile Alzheimer's disease, as it is not associated with any detectable morphological abnormality.
IDENTIFICATION OF LECTINS IN THE KINETIDS OF TETRAHYMENA PYRIFORMIS
Authors: KOVÁCS PÉTER , MÜLLER WERNER E. G. , CSABA GYÖRGY
Published: October 2002

Previously we described lectin‐like molecules in the ciliate Tetrahymena pyriformis; by application of synthetic neoglycoconjugates it is now shown that T. pyriformis contains considerable amounts of both a β‐d‐glucose‐ and a lactose‐specific lectin. No evidence for the presence of α‐d‐mannose‐, α‐d‐galactose‐ or of α‐l‐fucose‐specific lectins could be obtained. The two lectins, identified in T. pyriformis, are associated with the kinetids. During cell division the lectins disappear or become masked in the fission furrow. Therefore, we assume that these lectins are involved in the organization of the distribution pattern of the kinetids during cell division perhaps due to lectin—glycoprotein interactions.
CISPLATIN INHIBITS PINOCYTOSIS INDICTYOSTELIUM DISCOIDEUM
Authors: REDDY T.B.K , CHATTERJEE S.
Published: October 2002

The effects ofcis‐diamminedichloroplatinum(II) [cisplatin], a potential anticancer drug, were studied on pinocytotic functions in the cellular slime mouldDictyostelium discoideumby administering FITC‐dextran as a fluid phase marker. Cisplatin treatment at a concentration of 100 and 200 μg/ml for 1 h causes inhibition in pinocytotic uptake in growingDictyosteliumcells in a dose‐dependent manner. Cisplatin treatment induced the association of more actin with the cell cortex, thereby presumably restricting the flexibility of the cell membrane and inhibiting the formation of pinosomes. Ultrastructural analysis of cisplatin‐treated cells showed a lower number of pinosomes. These results have been discussed in the light of cisplatin's known actions that affect various cellular functions.
MODULATION OF INTERFERON γ INDUCED INCREASES IN CATHEPSIN B IN THP‐1 CELLS BY ADRENERGIC AGONISTS AND ANTAGONISTS
Authors: LI QINGDI , BEVER CHRISTOPHER T.
Published: October 2002

In order to investigate the possible modulation of macrophage function by the autonomic nervous system, the effect of adrenergic agonists and antagonists on interferon (IFN)‐γ‐induced increases in cathepsin B (CB) in a macrophage‐like cell line was studied. It has been shown previously that IFN‐γ induces increased CB activity in phorbol myristate acetate (PMA)‐primed THP‐1 cells. Isoproterenol (ISO) (10μm), a mixed β‐receptor agonist, increased the induction of CB activity in the cells but norepinephrine (10μm) and epinephrine (10μm), the α and β receptor agonists, had little effect. The addition of the mixed α‐receptor antagonist phentolamine (10μm) had no effect on ISO induced increases but the mixed β‐receptor antagonist propranolol (10μm) and the selective β1‐receptor antagonist atenolol produced significant inhibition. These results suggest that the activation of β‐receptors could be involved in the induction of CB activity in macrophages and provide a possible mechanism for the regulation of macrophage effector function by the autonomic nervous system. Dibutyryl cAMP (1mm) alone also induced increases in CB in THP‐1 cells, and H‐89 or HA1004 abrogated the effect of dibutyryl cAMP, suggesting that the effect of ISO on CB could be through the elevation of cAMP and the activation of cAMP‐dependent protein kinases.
MAPPING CELL WALL POLYSACCHARIDES OF LIVING MICROBIAL CELLS USING ATOMIC FORCE MICROSCOPY
Authors: GAD M. , ITOH ARIMICHI , IKAI ATSUSHI
Published: October 2002

Functionalized atomic force microscope tips were used to sense specific forces of interaction between ligand—receptor pairs and to map the positions of polysaccharides on a living microbial cell surface. Gold‐coated tips were functionalized with concanavalin A using a cross‐linker with a spacer arm of 15.6Å. It was possible to measure the binding force between concanavalin A and mannan polymers on the yeast (Saccharomyces cerevisiae) cell surface. This force ranged from 75 to 200pN. The shape of the force curve indicated that the polymers were pulled away from the cell surface for a fairly long distance that sometimes reached several hundred nanometres. The distribution of mannan on the cell surface was mapped by carrying out the force measurement in the force volume mode of atomic force microscopy (AFM). During the measurement, the maximum cantilever deflection after contact between the tip and the sample was kept constant at 10nm using trigger mode to keep the pressing force on the sample surface as gently as possible at a force of 180pN. This regime was used to minimize the non‐specific adhesion between the tip and the cell surface. Specific molecular recognition events took place on specific areas of the cell surface that could be interpreted as reflecting a non‐uniform distribution of mannan on the cell surface.
AN ATOMIC FORCE MICROSCOPIC EXAMINATION OF THE APICAL MEMBRANE OF THE MAMMALIAN GASTRIC GLAND
Authors: GEIBEL JOHN
Published: October 2002

The authors have examined the morphology of the apical membrane of living gastric glands from both the rat and rabbit with an atomic force microscope using both a conventional upright configuration and in the new inverted bioscope mode. Individual gastric glands were hand dissected and the apical membrane was exposed using a microsurgical approach. The split open glands allowed to access and directly image 4–6 cells with their apical axis available to the scanning tip of the atomic force microscope. All cells were scanned in a physiological Ringer solution at 37°C. The scans revealed that we could visualize both parietal and chief cells and to distinguish them via their unique apical topography. The parietal cells showed a variety of small canaliculi that were dispersed along the apical axis of the cell. Scans of chief cells revealed an apical surface that was covered with microvilli along the entire apical margin. The results of these studies show that it is indeed feasible to image living gastric glands at 37°C and to observe the surface topology of both the parietal and chief cell.
THE ATOMIC FORCE MICROSCOPE DETECTS ATP‐SENSITIVE PROTEIN CLUSTERS IN THE PLASMA MEMBRANE OF TRANSFORMED MDCK CELLS
Authors: EHRENHÖFER UWE , RAKOWSKA AGNIESZKA , SCHNEIDER STEFAN WERNER , SCHWAB ALBRECHT , OBERLEITHNER HANS
Published: October 2002

Plasma membrane proteins are supposed to form clusters that allow ‘functional cross‐talk’ between individual molecules within nanometre distance. However, such hypothetical protein clusters have not yet been shown directly in native plasma membranes. Therefore, we developed a technique to get access to the inner face of the plasma membrane of cultured transformed kidney (MDCK) cells. The authors applied atomic force microscopy (AFM) to visualize clusters of native proteins protruding from the cytoplasmic membrane surface. We used the K+channel blocker iberiotoxin (IBTX), a positively charged toxin molecule, that binds with high affinity to plasma membrane potassium channels and to atomically flat mica. Thus, apical plasma membranes could be ‘glued’ with IBTX to the mica surface with the cytosolic side of the membrane accessible to the scanning AFM tip. The topography of these native inside‐out membrane patches was imaged with AFM in electrolyte solution mimicking the cytosol. The plasma membrane could be clearly identified as a lipid bilayer with the characteristic height of 4.9±0.02nm. Multiple proteins protruded from the lipid bilayer into the cytosolic space with molecule heights between 1 and 20nm. Large protrusions were most likely protein clusters. Addition of the proteolytic enzyme pronase to the bath solution led to the disappearance of the proteins within minutes. The metabolic substrate ATP induced a shape‐change of the protein clusters and smaller subunits became visible. ADP or the non‐hydrolysable ATP analogue, ATP‐γ‐S, could not exert similar effects. It is concluded that plasma membrane proteins (and/or membrane associated proteins) form ‘functional clusters’ in their native environment. The ‘physiological’ arrangement of the protein molecules within a cluster requires ATP.
SIMS MICROSCOPY: METHODOLOGY, PROBLEMS AND PERSPECTIVES IN MAPPING DRUGS AND NUCLEAR MEDICINE COMPOUNDS
Authors: CLERC JÉRÔME , FOURRÉ CATHERINE , FRAGU PHILIPPE
Published: October 2002

Secondary ion mass spectrometry (SIMS) microscopy, a mass spectrometry method designed in the 1960s, offers new analytical capabilities, high sensitivity (ppm to ppb region), high specificity and improved lateral resolution, thus facilitating insight into many physiological and biomedical questions. Apart from the sample preparation and the physical characteristics of the detection, the biological model must also be considered.

SIMS analysis of diffusible ions and molecules requires strict cryogenic procedures which always begin by a flash‐freeze fixation. Cellular integrity can be checked by mapping the major element distributions since intra and extracellular ions are redistributed only in damaged cells. Cryofixing may be followed either by a freeze‐fracture methodology or by cryoembedding and dry‐cutting. Chemical sample preparation is only used for ions or molecules bound to fixed cell structures.

The use of scanning procedures ameliorates the lateral resolution and chromosome imaging has been reported with probe size of below 50nm. Absolute quantification can be derived for embedded specimen by using internal references included in tissue equivalent resins. The sensitivity is limited by the ionization yield of the tag element and may be further impaired when working at high mass resolution (≥5000) to eliminate interfering cluster ions.

SIMS drug mapping is usually performed after in vitro administration of a molecule to cell culture systems. Drug detection is accomplished indirectly by detecting a tag isotope naturally present or introduced by labelling, mainly with halogens,15N and14C. Molecular imaging with TOF‐SIMS is an appealing alternative especially for heavier compounds. We stress some biological problems through a critical review of published SIMS drug studies. SIMS proved useful in assessing the targeting specificity of nuclear medicine pharmaceutics, even after in vivo administration. The first microscopic evidence of a thionamide induced follicular blockade of the iodine organification process is presented in a human sample.
A COMPARISON OF THE ANTI‐HISTONE AND APOP‐TAG TECHNIQUE FOR DEMONSTRATING APOPTOSIS WITH OPTION FOR SILVER ENHANCEMENT
Authors: AL‐HAZZAA AMAL A. , BOWEN I. D. , BIRCHALL M. A.
Published: October 2002

A novel immunocytochemical method is presented for the qualitative detection of DNA fragmentation in apoptosis. Anti‐histone antibody is employed to localize exposed nucleosomal histones (H1, H2a, H2b, H3 and H4) rather than tagging the cut ends of fragmenting DNA as in conventional technique. The method was tested on squamous cell carcinoma of the larynx routinely fixed in formaldehyde and embedded in paraffin wax and compared with results obtained employing Apop‐Tag kit (Oncor).
HAPLOID MALE GERM CELLS SHOW NO SUSCEPTIBILITY TO TRANSFORMATION BY SIMIAN VIRUS 40 LARGE TUMOUR ANTIGEN IN TRANSGENIC MICE
Authors: NAYERNIA KARIM , SAMANI AMIR ABBAS , KLAPROTH SILKE , ENGEL WOLFGANG
Published: October 2002

Cell‐type specific tumorigenesis can be induced in transgenic mice by the directed expression of simian virus 40 (SV 40) large tumour antigen (TAg). In an attempt to determine the susceptibility of haploid male germ cells to neoplastic transformation by this oncogene, transgenic mice were generated that harboured a chimeric gene composed of the SV40 T antigen genes fused to the 2.3‐kb 5′ flanking sequences of the rat proacrosin gene. It was previously shown that this regulatory sequence is able specifically to direct the expression of CAT reporter gene in male germ cells with the onset of translation in early haploid male germ cells. The transgene showed regulated expression in male germ cells. Although T antigen immunostaining was detected specifically in spermatids, no testicular pathology was observed. This indicates that spermatids show no susceptibility to transformation by oncogene TAg. However, in about 10% of animals of two independent transgenic lines, we could find non‐testicular tumours in abdomen with a sarcoma‐like structure in advanced age which showed SV40 TAg expression.
CHANGES IN ENDOGENOUS POLYAMINE LEVELS ARE ASSOCIATED WITH DIFFERENTIATION IN DICTYOSTELIUM DISCOIDEUM
Authors: SARAN SHWETA
Published: October 2002

This is the first report correlating levels of polyamines and its fractions with differentiation in Dictyostelium discoideum. Temporal changes in endogenous levels of free, conjugated and bound putrescine, spermidine and spermine were analysed at critical stages of morphogenesis in this organism. No spermine was found at any given stage and putrescine was the most abundant polyamine. There was a sharp increase in the levels of both free (and total) and conjugated forms of putrescine and spermidine at the slug stage as compared to the growth phase. The levels of putrescine and spermidine were found to be higher in isolated prespore cells as compared to the prestalk cells. Remarkably, the levels of polyamine decreased at the early culminant stage. Data suggest that a moderate level of polyamines is needed for growth but it is important to have high levels of polyamines at the time of differentiation.
BISPHENOL A DIGLYCIDYL ETHER (BADGE) SUPPRESSES TUMOR NECROSIS FACTOR‐α PRODUCTION AS A PPARγ AGONIST IN THE MURINE MACROPHAGE‐LIKE CELL LINE, RAW 264.7
Authors: Nakamuta Makoto , Enjoji Munechika , Uchimura Koutaro , Ohta Satoshi , Sugimoto Rie , Kotoh Kazuhiro , Kato Masaki , Irie Takashi , Muta Tatsushi , Nawata Hajime
Published: October 2002

Bisphenol A diglycidyl ether (BADGE) is a newly described peroxisome proliferator‐activated receptor γ (PPARγ) antagonist in adipogenic cells. In contrast, in the macrophage‐like cell line RAW 264.7, BADGE, like the PPARγ agonist pioglitazone hydrochloride, not only increased promoter activity of the PPARγ‐luciferase reporter gene, but also suppressed lipopolysaccharide (LPS)‐induced tumor necrosis factor‐α (TNF‐α) production. These results suggest that BADGE is a PPARγ agonist in RAW 264.7 cells. Furthermore, overexpression of the coactivator p300 restored BADGE‐ or pioglitazone hydrochloride‐suppressed promoter activity of the nuclear factor‐kappa B (NF‐κB)‐luciferase reporter gene, suggesting that PPARγ may interfere with NF‐κB transcriptional activity via coactivator competition.
MYOSIN II REDISTRIBUTION DURING REAR RETRACTION AND THE ROLE OF FILAMENT ASSEMBLY AND DISASSEMBLY
Authors: Koehl Gudrun , Mcnally James G.
Published: October 2002

The literature to date suggests a role for myosin II in rear retraction, including evidence that myosin undergoes a characteristic ‘C’‐to‐spot redistribution at the cell posterior which is associated with retraction. Here we investigate the mechanism of both retraction and the ‘C’‐to‐spot using
MECHANICAL ASPECTS OF CELL SHAPE REGULATION AND SIGNALING
Authors: Goldmann Wolfgang H.
Published: October 2002

Physical forces play a critical role in cell integrity and development, but little is known how cells convert mechanical signals into biochemical responses. This mini‐review examines potential molecular mediators like integrins, focal adhesion proteins, and the cytoskeleton in the context of a complex cell structure. These molecules—when activated by cell binding to the extracellular matrix—associate with the skeletal scaffold via the focal adhesion complex. Vinculin is presented as a mechanical coupling protein that contributes to the integrity of the cytoskeleton and cell shape control, and examples are given of how mechanical signals converge into biochemical responses through force‐dependent changes in cell geometry and molecular mechanics.
Fertile Usnea Longissima in the Oregon Coast Range
Authors: Keon D. B.
Published: October 2002

Apothecia from Usnea longissima thalli collected in the Oregon Coast Range are described. Fertile U. longissima specimens have seldom been observed and rarely documented in the literature. A brief history of accounts in the literature is given, and possible reasons for the infrequent occurrence of apothecia are discussed. This is the first published account of fertile U. longissima specimens in the U.S. Pacific Northwest.
Carnivore Diversity in the Late Quaternary of Israel
Authors: Dayan Tamar
Published: October 2002

During the past 70,000 years, Israeli carnivore faunas have varied only slightly in richness (number of species), but widely in diversity (including the relative abundances of the different species). Human population growth, sedentism, and the beginning of agriculture are often considered to have caused habitat destruction toward the end of the Pleistocene that may have affected animal populations. However, patterns of changing carnivore diversities from three sites in the Mediterranean region of Israel correlate well with changes in precipitation: species diversity is higher during more humid phases and lower during drier phases. The environmental effect of sedentism may have accelerated the later drop in carnivore diversity but cannot account for fluctuations in diversity preceding it.
SEM Analysis of Quartz Sand Grain Surface Textures Indicates Alluvial/Colluvial Origin of the Quaternary “Glacial” Boulder Clays at Huangshan (Yellow Mountain), East-Central China
Authors: Helland P. E. , Huang Pei-Hua , Diffendal R. F.
Published: October 2002

Geomorphic features and Pleistocene deposits on Huangshan have been attributed to glaciation. Recent reassessment questions this interpretation. As part of the reassessment, quartz sand grains from deposits identified as glacial boulder clays (till composed of boulders in a clay or silt matrix) were analyzed by scanning electron microscope for evidence of their sedimentary history. Surface textures found on the boulder-clay grains were compared with those on grains with known sedimentary histories including glacial, grus, colluvial, and alluvial grains. The analysis shows that the grains lack typical glacial textures. The surface textures present indicate a complex history. Nonuniformly weathered grain surfaces point to chemical weathering of the source rock. This is supported by the deep weathering of the nonquartz clasts in the sand-sized fraction as well as in boulders at the outcrops. The close correspondence in surface-texture frequencies with those of the alluvial grains indicates an alluvial component to the grains’ history. The similarity with the colluvial grains and the outcrops’ structures suggest an alluvial/colluvial origin for the deposits. The history indicated by the surface textures agrees with the recent reassessment of the geomorphic features and points to warm climatic conditions in east-central China for at least part of the Pleistocene.
Interfaces for Refining Recursion and Procedures
Authors: Staples Mark
Published: October 2002

This paper presents novel definitions of interfaced recursion blocks, interfaced procedures, and interfaced recursive procedures for the Refinement Calculus. These definitions allow step-wise refinement rules to be formally stated and proved for these constructs. An interface is associated with a (recursive) call by preceding the body of the implementation by an assertion statement which says that the interface refines to the implementation. An interface will typically be a specification statement, but in principle can be any command. The theory and rules presented in this paper have been mechanised in the theorem prover Isabelle/ZF.
A Multi-formalism Approach for the Validation of UML Models
Authors: Dupuy Sophie , du Bousquet Lydie
Published: October 2002

Our approach is based on UML models. They are edited with the rational Rose
™
tool [Rat96] and complemented with annotations that state several constraints. The class diagram is the starting point of a translation process that produces formal specifications in Z [Spi92] and Lustre [CHP87]. The RoZ tool is used to translate the class diagram into Z automatically. The Z and Lustre specifications are used to validate the UML models by means of a prover and a testing environment.
Data Abstraction Techniques in the Validation of CSP-OZ Specifications
Authors: Wehrheim Heike
Published: October 2002

CSP-OZ is an integrated formal method which combines the state-oriented specification language Object-Z with the process algebra CSP, thereby allowing a description of static as well as dynamic aspects of a system. Checking correctness of CSP-OZ specifications can be done via a
translation
into (FDR-)CSP, on which automatic verification can be performed with the FDR model checker if the state space of the resulting CSP process is not too large to be processed. This paper investigates how
data abstraction
techniques can be used to bring a translated specification within range of automatic verification.
Abstraction and Testing in CSP
Authors: Schneider Steve
Published: October 2002

Restricted views of process behaviour result in a form of abstraction which is useful in the construction of specifications involving fault-tolerance and atomicity. This paper presents an operational characterisation of abstraction for refusable and non-refusable events in terms of testing. This view is a generalisation of standard notions of testing, and is given a new denotational characterisation encapsulated within the CSP denotational semantics. It informs, reinforces and extends the traditional denotational approach to abstraction.
Safe retroperitoneal endoscopic resection of pheochromocytomas
Authors: Berends Frits J. , Van Der Harst Erwin , Giraudo Giuseppe , Terkivatan Türkan , Kazemier Geert , Bruining Hajo A. , De Herder Wouter W. , Bonjer H. Jaap
Published: October 2002

Although endoscopic adrenalectomy is advocated for small adrenocortical tumors, questions remain about the safety of endoscopic retroperitoneal resection of pheochromocytomas. In this study we evaluated the outcome of retroperitoneal endoscopic adrenalectomy for pheochromocytoma. Between June 1995 and September 1999 we performed 18 retroperitoneal endoscopic adrenalectomies for a pheochromocytoma or paraganglioma. All patients received adequate α‐adrenergic blockade. The adrenal vein was ligated at the end of the procedure. Operative blood pressure values were recorded and evaluated. Altogether 15 patients (11 women, 4 men; mean age 47.2 years) were operated on for 17 pheochromocytomas and 1 extraadrenal tumor (4 right, 11 left, 3 bilateral). One female patient was operated on at 13 weeks’ gestation. Hypertensive episodes at operation were seen in 4 (26.7%) patients, and tachycardia occurred in 5 (33%). Hemodynamic changes could be corrected in all cases using simple measures without morbidity or detrimental effects. The mean operating time was 125 minutes (80–180 minutes), and the conversion rate was 5.6% (1/18). The median hospital stay was 5 days (3–28 days). Morbidity was 20% (3/15). Endoscopic retroperitoneal adrenalectomy for pheochromocytoma is safe and effective, and it is associated with limited morbidity.
Computer‐generated trauma management plans: Comparison with actual care
Authors: Clarke John R. , Hayward Catherine Z. , Santora Thomas A. , Wagner David K. , Webber Bonnie L.
Published: October 2002

TraumAID is a computer‐based decision aid that uses decision rules and logical deduction to generate management plans for the initial definitive management of injured patients; its use is currently confined to assessing penetrating thoracoabdominal injuries in nonpregnant adults. These management plans were compared to trauma center care in an American urban medical school hospital. The TraumAID program was available to trauma chief residents for patient care during the “golden hour.” Resulting changes in plans were documented by the residents. For 15 months the management plans for all applicable patients were documented serially, as were computer plans and outcomes. The sequential care and computer‐generated care plans were then blinded and judged by three other trauma surgeons as to acceptability and preference. A consecutive series of 97 patients was evaluated. The residents used the computer for 40 cases during patient care. In 5 of the 40 cases, they altered their evaluation, diagnosis, or treatment; in none of these 5 was the alteration judged an error. Of the 97 patients, 10 had adverse outcomes, 2 of which were judged potentially avoidable, with unacceptable errors in management. TraumAID’s plans were acceptable for both. In 31 cases previously managed by the judges themselves, the TraumAID plans were preferred by the judge to the care he or she had provided, by a ratio of 25:6 (p<0.01). In a preliminary assessment, computer‐generated, patient‐specific protocols for the acute management of injuries were preferred to actual care previously given by the judges themselves and were associated with improved care and potential improvement in outcome.
Effect of the presence of hepatitis B e antigen on prognosis after liver resection for hepatocellular carcinoma in patients with chronic hepatitis B
Authors: Kubo Shoji , Hirohashi Kazuhiro , Yamazaki Osamu , Matsuyama Mitsuharu , Tanaka Hiromu , Horii Katsuhiko , Shuto Taichi , Yamamoto Takatsugu , Kawai Shuichi , Wakasa Kenichi , Nishiguchi Shuhei , Kinoshita Hiroaki
Published: October 2002

We examineded the clinical effects of serum hepatitis B e antigen (HBeAg) positivity on clinicopathologic findings and prognosis after liver resection for hepatocellular carcinoma (HCC) in patients with chronic hepatitis B. A series of 56 patients who underwent curative resection were divided into two groups: 25 HBeAg‐positive patients (group 1) and 31 HBeAg‐negative patients (group 2). The mean age was significantly lower in group 1 than in group 2 (p=0.0021), and the proportion of patients with symptoms was significantly higher in group 1 than in group 2 (p=0.037). There were no significant differences in other clinical findings between the two groups, including laboratory test results, coexisting medical conditions, and operative methods. Although tumor size, degree of differentiation of the main tumor, and the prevalence of vascular invasion did not differ between the groups, the prevalence of intrahepatic metastasis and the proportion of patients with active hepatitis were significantly higher in group 1 than in group 2 (p=0.009 and p=0.043, respectively). Tumor‐free and cumulative survival rates were significantly lower in group 1 than in group 2 (p=0.022 and p=0.0001, respectively). Multivariate analysis of various possible risk factors demonstrated serum HBeAg positivity to be an independent risk factor for recurrence [risk ratio (RR) 2.49; 95% confidence interval (CI) 1.12–5.49; p=0.032] and an independent unfavorable factor for the survival time (RR 7.58; 95% CI 2.10–27.8; p=0.0020). We concluded that the prognosis after liver resection for HCC is worse for HBeAg‐positive patients than for HBeAg‐negative patients.
Pylorus‐preserving gastrectomy: Effect on resistance through the sphincter of Oddi compared to conventional distal gastrectomy in dogs
Authors: Naito Hiroo , Shibata Chikashi , Ohtani Noriya , Funayama Yuji , Fukushima Kouhei , Matsuno Seiki , Sasaki Iwao
Published: October 2002

Bile stasis is an important etiologic factor in the high incidence of postgastrectomy gallstone disease (PGGD). Our previous study showed that duodenal, but not prepyloric, transection disturbed the motility of the sphincter of Oddi (SO) in anesthetized dogs. We had developed pylorus‐preserving gastrectomy (PPG), in which the anal margin of the resected stomach is the prepyloric portion, not the duodenum. The present study evaluated the usefulness of PPG for reducing bile stasis, which may induce PGGD. We examined the resistance of bile flow through the SO using dogs that had undergone either PPG (n=5) or conventional distal gastrectomy (B‐I) (n=5). Four weeks after gastrectomy we anesthetized the animals and compared the basal and volume load‐induced pressure in the common bile duct (CBD) between groups with or without administration of cholecystokinin‐8 (CCK8). Flow resistance of the SO was evaluated by measuring flow volume through the SO following a graded pressure load to the CBD. The basal pressure and the threshold pressure to open the SO were significantly lower in PPG dogs than in B‐I dogs independent of CCK8 administration. There were no significant differences between groups in regard to volume load‐induced pressure elevation or the resistance of the SO. These results indicate that PPG may be more useful for reducing the incidence of PGGD than conventional distal gastrectomy, possibly through attenuating resistance to bile flow.
Evaluation of a new composite prosthesis (PL‐PU99) for the repair of abdominal wall defects in terms of behavior at the peritoneal interface
Authors: Bellón Juan M. , García‐Carranza Alberto , Jurado Francisca , García‐Honduvilla Natalio , Martín Antonio Carrera‐San , Buján Julia
Published: October 2002

This study was designed to evaluate the behavior of a new composite polypropylene‐polyurethane (PL‐PU99) when placed in direct contact with the visceral peritoneum during the repair of an abdominal wall defect. Full‐thickness abdominal wall defects (7×5 cm) were created in 36 anaesthetized white New Zealand rabbits. The defects were repaired with polypropylene prostheses or PL‐PU99 prostheses (comprised of PL and a polyurethane sheet glued to the PL with acrylic adhesive) to establish two study groups (n=18 each). Animals were sacrified 14, 30, or 90 days after implantation and prosthesis/surrounding tissue specimens were subjected to light and electron microscopy and morphometric analysis of the newly formed peritoneum. Immunohistochemical analysis was performed using the rabbit specific monoclonal antibody RAM‐11. The biomechanical strength of the implants was also assessed. Firm adhesions were detected in the PL implants, whereas adhesions were practically non‐existent in the PL‐PU99 implants. The surface area covered by adhesions was greater (p<0.01) in the PL group (7.36 vs. 0.11 cm2). The neoperitoneum formed after the implantation of a PL prosthesis was disorganized in structure, whereas that formed at the interface with the PL‐PU99 prosthesis was structurally similar to the host peritoneum. The excellent performance of the PL‐PU99 prosthesis shown in this study warrants further investigation into its use for the repair of abdominal wall defects when the prosthetic patch needs to be placed in contact with the intestinal loops.
Clinical characteristics of hepatitis B core antibody‐positive hepatocellular Carcinoma
Authors: Nakai Takuya , Koh Kenzo , Kawabe Takashi , Shiraishi Osamu , Okuno Kiyotaka , Yasutomi Masayuki
Published: October 2002

The pathology and prognosis of hepatitis B surface antigen (HBsAg)‐positive hepatocellular carcinoma (HCC) and hepatitis C virus antibody (HCVAb)‐positive HCC is well documented. However, patients with HBsAg‐negative/hepatitis B core antibody (HBcAb)‐positive HCC are included with non‐B non‐C disease and have been characterized independently. A series of 125 patients who had undergone hepatectomy for HCC were divided into three groups and compared. The HBsAg group comprised 25 HBsAg‐positive patients, the HCV group comprised 70 HCVAb‐positive patients, and the HBcAb group comprised 22 HBcAb‐positive/HBsAg‐negative patients. Eight patients of negative virus markers were excluded in this study. Tumors were larger in the HBcAb group (6.2 cm) than in the HBsAg (4.4 cm) and HCV (3.7 cm) groups. Disease‐free 1‐, 3‐, and 5‐year survival rates were, respectively, 75.0%, 57.1%, and 57.1% in the HBcAb group; 60.9%, 41.8%, and 41.8% in the HBsAg group; and 88.0%, 54.0%, and 37.8% in the HCV group. HBcAb‐positive HCC patients had larger tumors, but their prognosis was relatively good. Although HBsAg and HCVAb are used for conventional screening of patients with hepatic disorders, we believe that screening is also necessary in patients with positive HBcAb titers for early detection of HCC.
Charles-Michel Billard (1800–1832): Pioneer of Infant Pathology
Authors: Beckwith J. Bruce
Published: October 2002

How very wide, and, at the same time, an almost unbeaten track, lies open to investigate the diseases of new-born infants by an attentive and accurate observation in dissection after death, as well as while they are living.

Giovanni Battista Morgagni, 1761 [1]
Free‐listed items are effective cues for eliciting additional items in semantic domains
Authors: Brewer Devon D. , Garrett Sharon B. , Rinaldi Giovanni
Published: October 2002

This study tested a cueing procedure for enhancing recall in semantic domains based on associative processes inferred from semantic clustering. Participants first free listed items exhaustively from a semantic domain (fruits or drugs). Then, to aid recall of additional items from the domain, participants received either the items they free listed as semantic cues (to trigger semantically similar items) or alphabetic cues (to trigger items beginning with a particular letter). Participants' strong semantic clustering and weak alphabetic clustering in free listing confirmed previous research on associative processes. By several measures, free‐listed items as semantic cues elicited moderately more additional items than alphabetic cues. Semantic cues elicited an appreciable proportion of items that would not have been identified at the aggregate level through free listing alone. These results indicate that using free‐listed items as semantic cues can be a useful adjunct for ethnographic applications of free listing. Copyright © 2002 John Wiley & Sons, Ltd.
A comparison of mental and physical context reinstatement in forensic interviews with alleged victims of sexual abuse
Authors: Hershkowitz Irit , Orbach Yael , Lamb Michael E. , Sternberg Kathleen J. , Horowitz Dvora
Published: October 2002

Forensic interviews with 142 alleged victims of sexual abuse, ranging from 4.0 to 13.5 years of age, were conducted under three different interviewing conditions: at the scene of the incidents (Physical Context Reinstatement; PCR group), in the investigator's office with mental context reinstating instructions (MCR group), and in the office without contextual cueing (Control group). Children in the PCR, MCR, and Control groups did not differ significantly with respect to the total number of informative details reported. Children in the MCR condition provided more detailed responses to the main invitation and in their first narrative than did children in the PCR condition, however. They also provided proportionally more detailed responses to open‐ended invitations and fewer details in response to directive prompts than did children in the two other conditions. The MCR procedures were thus associated with greater improvements in the quality of information retrieval than were the PCR procedures. In all interviewing conditions, children aged 7 to 13 years provided significantly more details than 4‐ to‐6‐year‐old children did. The youngest children provided fewer details in response to invitations and directive utterances, and proportionally more details in response to option‐posing and suggestive utterances. No significant interactions between age and interviewing condition were apparent. Published in 2002 by John Wiley & Sons, Ltd.