bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of a system for the perfusion of isolated, rodent organs
Authors: Thein E. , Sevilmis G. , Muenzing S. , Hammer C. , Messmer K.
Published: March 2003

Abstract: Perfusion of isolated organs is a common experimental approach. However, the surfaces of the perfusion system might alter the components of the blood and thereby negatively affect organ function. The aim of this study was to minimize the influence of the perfusion system on the blood components and to evaluate the system. Pressure and flow in the perfusion system consisting of a roller‐pump, reservoir, oxygenator, hemo‐filter and bubble‐trap with a total tubing length of 4.5 m are controlled by a computer software (dasylab, Datalog, Moenchengladbach, Germany) via a transducer connected to the system. The organ to be perfused is positioned under a microscope (Orthoplan, Leica, Bensheim, Germany), allowing the investigation of microcirculatory parameters. The images raised are recorded on video tapes. To evaluate the system it was perfused with human blood (Hct 28 to 30%) for 90 min. Heparin (n = 6) or citrate (n = 6) served as anti‐coagulants. The disappearance of cells from the blood was determined at time points 0, 1, 5, 10, 15, 20, 30, 45, 60, 75 and 90 min by means of a cell counter (AC T8, Coulter Beckmann, Krefeld, Germany). Cell activation was assessed by analysis of the expression of L‐ and P‐selectin and CD11b. The activation of the complement system was examined by measuring the serum levels of the complement factors C3c and C4. There was no significant loss or activation of the blood cells at any of the above given time points. The serum levels of the complement factors remained within the physiological range and showed no changes throughout the whole experiments. Thus, the perfusion system does not have a negative influence on the blood and its individual components, and is therefore a reliable tool for perfusion experiments.
High avidity antibodies to fetal pig pancreas endocrine cells transfer rejection but are not normally generated to fetal pig pancreas xenografts
Authors: Fox Annette , Mountford Joanne , Braakhuis Andrea , Harrison Leonard C.
Published: March 2003

Fox A, Mountford J, Braakhuis A, Harrison LC. High avidity antibodies to fetal pig pancreas endocrine cells transfer rejection but are not normally generated to fetal pig pancreas xenografts. Xenotransplantation 2002; 9: 382–392. © Blackwell Munksgaard, 2002

Previous studies on the contribution of T cell‐dependent antibody (Ab) to non‐vascular xenograft rejection have yielded conflicting results, being confounded by the presence of recipient T cells and the use of different tissues and immunizing regimens to generate Ab. In the present study, the effect of adoptive transfer of Ab on fetal pig pancreas (FPP) and pig PK15 cell xenografts was examined in T cell‐deficient severe combined immune deficiency (SCID) mice. T cell‐dependent Abs raised by hyperimmunization with different cell types and by FPP transplantation were compared.

Ab raised by hyperimmunization with pig thymocytes exhibited strong binding to pig thymocytes and PK15 cells but did not transfer FPP rejection. IgG1 and IgM, but not IgG3, Abs bound strongly to FPP exocrine and connective tissue, whereas binding to endocrine cells in vitro and in vivo was weak or absent. This pattern of Ab binding was similar to that observed after transplanting FPP into BALB/c mice. Furthermore, serum recovered from BALB/c mice 20 days after FPP transplantation bound strongly to non‐endocrine but not endocrine cells and did not transfer FPP rejection. In contrast, serum from mice hyperimmunized with PK15 cells bound strongly to PK15 cells and transferred rejection of intraperitoneal PK15 cells. Furthermore, this serum contained IgG1 and IgM Abs that bound strongly, and IgG3 Abs that bound weakly, to endocrine cells in FPP, and also transferred rejection of FPP in SCID mice. These results indicate that endocrine cells express low concentrations of xenoreactive Ab epitopes and that high Ab concentrations and/or high avidity Abs are required for sufficient endocrine cell binding to cause damage and rejection in the immunodeficient mouse model. Such Abs are not elicited by transplanting FPP into immunocompetent mice. Nevertheless, a contribution of Ab to rejection in immunocompetent mice cannot be excluded.
Promotion of xenogeneic hematopoietic chimerism in rodents by mononuclear phagocyte depletion
Authors: Cheng J. , Glaser R. M. , Kruger‐Grey H. , White‐Scharf M. E. , Cooper D. K. C. , Thall A. D.
Published: March 2003

Cheng J, Glaser RM, Kruger‐Grey H, White‐Scharf ME, Cooper DKC, Thall AD. Promotion of xenogeneic hematopoietic chimerism in rodents by mononuclear phagocyte depletion. Xenotransplantation 2002; 9: 402–409. © Blackwell Munksgaard, 2002

The successful establishment of tolerance toward pig tissues in primates through hematopoietic progenitor cell engraftment is restricted by the rapid disappearance of these cells in the recipient following infusion. We developed and tested the hypothesis that phagocytes of the reticuloendothelial system are responsible for the rapid clearance of infused pig hematopoietic cells using a mouse model. Mice received non‐myeloablative conditioning and, on various days, were injected with medronate‐encapsulated liposomes (M‐L) or control blank liposomes, followed by the intravenous infusion of miniature swine hematopoietic cells. M‐L were well‐tolerated in mice (n=100) at levels that deplete mononuclear phagocytes. Depletion of mononuclear phagocytes in normal Balb/c mice as well as in severe combined immune deficient mice increased the accumulation of pig hematopoietic cells in the bone marrow (BM) by 10‐fold when measured 24 h after the infusion of the cells. Colony‐forming unit analysis showed an increased accumulation of pig hematopoietic progenitors in the BM of mice that were infused with medronate‐liposomes. We conclude that depletion of mononuclear phagocytes by M‐L has the potential to lower the barrier to the establishment of mixed chimerism and tolerance induction in xenotransplantation.
Intraseasonal variation in immune defence, body mass and hematocrit in adult house martins Delichon urbica
Authors: Christe Philippe , Møller Anders Pape , González Guillermo , De Lope Florentino
Published: March 2003

The intensity of parasite infections often increases during the reproductive season of the host as a result of parasite reproduction, increased parasite transmission and increased host susceptibility. We report within‐individual variation in immune parameters, hematocrit and body mass in adult house martinsDelichon urbicarearing nestlings in nests experimentally infested with house martin bugsOeciacus hirundinisand birds rearing nestlings in initially parasite‐free nests. From first to second broods body mass and hematocrit of breeding adult house martins decreased. In contrast leucocytes and immunoglobulins became more abundant. When their nests were infested with ectoparasites adults lost more weight compared with birds raising nestlings in nests treated with pyrethrin, whereas the decrease in hematocrit was more pronounced during infection with blood parasites. Neither experimental infestation with house martin bugs nor blood parasites had a significant effect on the amount of immune defences.
Direct suppressive effects of weak magnetic fields (50 Hz and 162/3 Hz) on melatonin synthesis in the pineal gland of Djungarian hamsters (Phodopus sungorus)
Authors: Brendel H. , Niehaus M. , Lerchl A.
Published: March 2003

In many investigations performed thus far on rodents, a suppression of melatonin synthesis was observed when animals were exposed to weak magnetic fields. However, among the several issues not yet resolved is the question of whether the observed changes are caused by direct effects on the pineal gland or by indirect effects, e.g., at the level of the eyes. We, therefore, performed a series of experiments in which direct effects of weak magnetic fields were studied in isolated pineal glands of Djungarian hamsters (Phodopus sungorus). After sacrifice of animals during morning hours, pineal glands were removed and placed individually into glass chambers that were perfused with oxygenated buffer. Experiments (n=8) lasted for 8 hr. Magnetic fields (162/3 or 50 Hz at 86 μTesla) were generated by Helmholtz coils, and were present during the entire period. In each experiment, 12 exposed, and 12 sham‐exposed, pineal glands were placed individually in glass chambers, which were surrounded by identical coils. Because of the design of the coils (bifilament), and the experimental setup (black box), the experimentator was not aware which coil was activated until the results were obtained. After 3.25 hr of adaptation, melatonin production was stimulated by isoproterenol (10−7 M) for 30 min. Eluted fractions were collected, and melatonin concentrations were measured by radioimmunoassay. Maximum melatonin production was achieved after 5–7 hr. In all experiments, maximum melatonin concentrations were lower in the exposed groups compared with the sham‐exposed controls. Statistical analyses for each frequency showed significant suppressive effects at 162/3 Hz (P<0.01), and 50 Hz (P<0.001). It is concluded that the suppressive effects of magnetic fields on the synthesis of melatonin are a result of primary mechanisms at the level of the pineal gland.
Understanding cytotoxic T‐lymphocyte escape during simian immunodeficiency virus infection
Authors: O'Connor David , Friedrich Thomas , Hughes Austin , Allen Todd M. , Watkins David
Published: March 2003

Summary: Infection of rhesus macaques with simian immunodeficiency virus (SIV) is an excellent model system for studying viral adaptation to immune responses. In this review, we discuss how the SIV‐infected macaque has provided unequivocal evidence for cytotoxic T‐lymphocyte (CTL) selection of viral escape variants. This improved understanding of CTL escape may influence human immunodeficiency virus (HIV) vaccine design as well as our understanding of HIV pathogenesis.
Host–tumor interactions during the regression of a rat histiocytoma, AK‐5
Authors: Khar Ashok , Anjum Rana
Published: March 2003

Summary: An efficient immune response comprises a highly intricate, integrated circuitry involving both the cellular and the humoral arms of the immune system of the host interacting with the rapidly proliferating microcosm of the tumor. The mechanism of tumor rejection involving multiple arms of the immune system was reviewed in a spontaneously regressing rat histiocytoma, AK‐5, an autologous tumor–host system. Intraperitoneal tumor transplantation leads to death in all animals, whereas subcutaneously (s.c.) transplanted tumor undergoes regression in 70% of animals. Regression of the tumor occurs by both apoptosis and necrosis, and natural killer (NK) cells were identified as the chief effectors mediating tumor cell death in vivo. A type 1 helper T cell (Th1)‐driven cytokine cascade played a crucial role in enhancing cellular functions at the tumor site and obtaining a sufficient immune response for tumor rejection. The s.c. tumor‐bearing hosts were shown to produce a factor which induced apoptosis in tumor cells, mediating tumor rejection. This review emphasizes the daunting complexities and interesting liaisons between the host immune system and the tumor, highlighting the work from our laboratory, and stressing that it is the interaction of several factors in concert or antagonizing each other that is responsible for the spontaneous regression of a tumor.
Regulation of IL‐4 production in mast cells: a paradigm for cell‐type‐specific gene expression
Authors: Weiss Deborah L. , Brown Melissa A.
Published: March 2003

Summary: The role of interleukin (IL)‐4 as an important immunomodulatory cytokine is well established. IL‐4 exhibits a highly restricted pattern of expression by cells of distinct lineages. The cell types that produce IL‐4 are located in anatomically distinct locations (e.g. circulating T cells vs. fixed tissue mast cells) and thus have access to different IL‐4‐responsive target cells. In addition, these cells appear to regulate IL‐4 expression in cell‐type‐specific ways. These findings suggest that an understanding of IL‐4 gene regulation in T and mast cells could provide the means to specifically control IL‐4 release in a lineage‐ and site‐specific manner. In this article we review the current knowledge regarding the cell‐type specific regulation of IL‐4 gene expression in mast cells and compare this to what has been defined in T cells. We show that there are distinct yet parallel events that control developmentally determined chromatin modifications, allowing accessibility of the locus, and provide the potential for transcription. In differentiated cells, a subset of unique cell activation signals initiates the cascade of events that lead to transcriptional activation of the IL‐4 gene.

This work was supported by the National Science Foundation (DLW), the National Institutes of Health and the Multiple Sclerosis Society (MAB). We appreciate the technical and intellectual contributions of many colleagues including Doris Powell, John Hural, Tammy Nachman, Ben Hock, David Tara, Greg Henkel, Susan Lee, Millie Kwan, Melanie Sherman and Ginny Secor.
Hematopoietic stem cells and their precursors: developmental diversity and lineage relationships
Authors: Dzierzak Elaine
Published: March 2003

Summary:  Within the context of the developing embryo, restrictions in cell lineage potential occur through cell–cell interactions and signaling molecules, leading to changes in genetic programs and to the emergence of disparate tissues containing functionally distinct cell types including somatic stem cells. Tissue maintenance in the adult is thought to occur through specific stem cells, and in the case of the hematopoietic system, through hematopoietic stem cells (HSCs). These cells arise in midgestation within the region of the embryo containing the dorsal aorta, gonads, and mesonephros (AGM) and are thought to maintain a distinct hematopoietic lineage‐restricted fate. However, recent transplantation experiments suggest that within the adult, HSCs previously thought to be restricted can, under certain circumstances, display unexpected lineage potentials. With these surprising and controversial results, it is becoming apparent that a better understanding of the developmental processes, molecular programs and lineage relationships leading to the emergence of adult stem cells will provide insight into the incremental steps involved in lineage determination, and perhaps possibilities for the manipulated differentiation of stem cells. The most widely studied, accessible stem cell and cellular differentiation hierarchy is that of the hematopoietic system. With the issue of stem cell potential in the forefront, the focus of this review is on the development of the hematopoietic system: how HSCs arise in the embryo, the lineage relationships of hematopoietic cells as they are generated, and the identification of precursor cells fated to the hematopoietic lineage throughout ontogeny.
Ecstasy‐induced toxicity in rat liver
Authors: Beitia G. , Cobreros A. , Sainz L. , Cenarruzabeitia E.
Published: March 2003

Abstract: Background/Aims: The aim of the present study was to examine the effects of single and repeated administration of 3,4‐methylenedioxymethamphetamine (MDMA, “ecstasy”) on rat liver. Methods: Animals were given an acute (20 mg/kg) and repeated (20 mg/kg, b.i.d., for 4 consecutive days) intraperitoneal dose of MDMA, and at various times after administration the hepatic and serum determinations were made. Results: The effect of acute MDMA administration included increased triglyceride and cholesterol levels and an increase in all enzyme activities 6 h post administration. The toxic effect of MDMA was also observed in other hepatic processes. Glycogen content showed a marked decrease, which was accompanied by a decrease in serum glucose levels. No significant changes in lipid peroxidation and hepatic GSH content were observed. In contrast, multiple MDMA administration produced some evidence of oxidative stress, namely, increased MDA content and decreased GSH content, a small decrease in liver glycogen at 3 h recovering 6 h post dose, no effect on blood glucose and increased AST and ALP activities but no effects on ALT activity. Seven days after the last MDMA injection a tendency towards recovery was shown. Conclusion: Our results show that the liver toxicity caused by MDMA administration involves several mechanisms.
Growth inhibition of liver metastases by the anti‐angiogenic drug TNP‐470
Authors: Gervaz Pascal , Scholl Beatrix , Padrun Vivianne , Gillet Michel
Published: March 2003

Abstract: Objective: This study was undertaken in order to assess the efficacy of a potent angiogenesis inhibitor, TNP‐470, on tumor growth in a syngeneic rodent model of liver metastases from colorectal cancer. Background: New blood vessel formation is a prerequisite for primary and metastatic tumor growth. TNP‐470, a synthetic derivative of fumagillin when subcutaneously transplanted into nude mice, inhibits endothelial cell proliferation and migration, as well as the growth of various human cancers. However, the antitumor effect of this drug has not been studied in models reproducing a natural metastatic environment. Since the liver provides an extensive vascular bed for secondary tumor growth, an anti‐angiogenic strategy may therefore be less efficient for treating hepatic metastases than primary tumors. Methods: 107 DHD K12 colon carcinoma cells were injected intrasplenically into syngeneic BD IX rats to produce diffuse liver metastases. TNP‐470 (30 mg/kg/day) was administered on alternate days starting 4 days after tumor implantation. The animals were sacrificed after 4 weeks and their livers were processed for histologic examination. In both the treatment and control groups (n=7), tumor volume was determined using a computerized analytical system, and tumor microvessel density was measured by immunostaining with anti‐von Willebrand Factor monoclonal antibody. Results:In vitro, TNP‐470 demonstrated a direct toxicity towards the DHD K12 cell line with an IC50 of 0.1 μg/ml. Metastases were present in all animals from both groups. Liver weight (15.2 g vs 11.7 g, p=0.01), and tumor volume (1218 mm3 vs 406 mm3, p=0.03) were significantly reduced in the TNP‐470 group compared to the control group. Tumor microvessel density was not statistically different between the two groups (67 vs 63 microvessels/×200 field, p=0.41). Conclusion: TNP‐470 inhibits the growth of liver metastases in a syngeneic rat model of colorectal cancer. The mechanism responsible for this effect remains unclear, but may involve a combination of anti‐angiogenic and direct cytotoxic effects.
Enhanced expression of endothelin receptor subtypes in cirrhotic rat liver
Authors: Yokomori Hiroaki , Oda Masaya , Ogi Mariko , Kamegaya Yoshitaka , Tsukada Nobuhiro , Nakamura Masahiko , Ishii Hiromasa
Published: March 2003

Abstract: Background/Aim: A number of vasoactive substances have been implicated as potential mediators of intrahepatic portal hypertension. Endothelin (ET)‐1 has been suggested to be involved in the regulation of hepatic microcirculation and development of portal hypertension. The aim of this study was to clarify the localization of two subtypes of ET receptors, ET A (ETaR) and B receptors (ETbR), in normal rat liver, and how the receptor expressions are altered in CCl4‐induced cirrhotic rat liver. Methods: Liver specimens were examined immunohistochemically after reacting with anti‐ETaR and anti‐ETbR rabbit polyclonal antibodies. Immunogold staining was also performed using the same antibodies, and examined under light and electron microscopy. Results: In normal rat liver, immunohistochemistry revealed expression of ETaR and ETbR on the hepatic sinusoidal lining cells. By immunogold electron microscopy, electron‐dense gold particles indicating the presence of ETaRs were localized mainly on hepatic stellate cells (HSCs) and to a lesser extent on sinusoidal endothelial cells (SECs), while ETbRs were expressed equally intensely on HSCs and SECs. In cirrhotic animals, both ETaR and ETbR increased significantly on HSCs, while there were no significant increases in either receptor on SECs. Conclusions: In the normal state, HSCs possess both ETaRs and ETbRs, while SECs mainly possess ETbRs. In cirrhosis, endothelins may exert more intense effects on HSCs via the enhanced ETaRs and ETbRs, causing an increase in hepatic sinusoidal microvascular tone.
Molecular cloning of three nonhuman primate follicle stimulating hormone β‐subunit cDNAs
Authors: Wolfgang M.J. , Grendell R.L. , Golos T.G.
Published: March 2003

The follicle stimulating hormone (FSH) β‐subunit cDNAs were cloned and sequenced for an old world primate, the rhesus monkey (Macaca mulatta), and two New World primates, the common marmoset (Callithrix jacchus) and pygmy marmoset (Cebuella pygmaea). The cDNA and predicted amino acid sequences of the rhesus monkey FSH β‐subunit were related most closely to the human FSH β‐subunit (>96% identity). The common and pygmy marmosets have identical FSH β‐subunit cDNAs, whereas the marmoset FSH β‐subunit diverges from the rhesus and human molecules with less than 93% identity. These results have significance for the implementation of assisted reproductive technologies in the nonhuman primate as well as the evolution of genes encoding reproductive hormones.
Effects of chair restraint on the strength of the tibia in rhesus monkeys
Authors: Hutchinson Teresa M. , Bakulin Alexy V. , Rakhmanov Alexander S. , Martin R. Bruce , Steele Charles R. , Arnaud Sara B.
Published: March 2003

To determine the effects of the relative inactivity and unloading on the strength of the tibias of monkeys, Macaca mulatta, we used a non‐invasive test to measure bending stiffness, or EI (Nm2), a mechanical property. The technique was validated by comparisons of in vivo measurements with standard measures of EI in the same bones post‐mortem (r2=0.95, P<0.0001). Inter‐test precision was 4.28±1.4%. Normative data in 24 monkeys, 3.0±0.7 years and 3.6±0.6 kg, revealed EI to be 16% higher in the right than left tibia (4.4±1.6 vs. 3.7±1.6 Nm2, P<0.05). Five monkeys, restrained in chairs for 14 days, showed decreases in EI. There were no changes in EI in two chaired monkeys that lost weight during a 2‐week space flight. The factors that account for both the decreases in bone mechanical properties after chair restraint at 1 g and lack of change after microgravity remain to be identified. Metabolic factors associated with body weight changes are suggested by our results.
Prey preference and reproductive success of the generalist predatorOrius laevigatus
Authors: Venzon Madelaine , Janssen Arne , Sabelis Maurice W.
Published: March 2003

In theory, selection favours predators that select prey in order to maximise reproductive success. We studied the association between preference and performance of the generalist predatorOrius laevigatuswith respect to two prey species: spider mites (Tetranychus urticae) and western flower thrips (Frankliniella occidentalis). Under ample prey supply, the predators had higher maximum reproductive success (measured as intrinsic population growth rater) on thrips than on spider mites; hence thrips represent a higher prey quality to the bugs. This was at odds with the observed preference of the predatory bug for plants (patches) with high densities of spider mites to plants with moderate densities of thrips in release‐recapture experiments. Thus, prey quality does not suffice to explain the preference of predators for plants with prey. The quality of a patch as an oviposition site (i.e. the number of eggs produced on a patch per bug per day) also did not match preference patterns. Hence, patch preference was not correlated to prey quality or oviposition rate on prey patches. However, patch productivity, i.e. the total number of offspring surviving until adulthood that can be produced by one female on a patch, was correlated with preference. This was further tested by offering the predators a choice between plants with high densities of spider mites and plants with high densities of thrips in an independent set of release‐recapture experiments. These two types of prey patches were found equivalent in terms of patch productivity. Indeed, the predators showed no preference for either of the two types of patches, which is in agreement with our predictions. This suggests that the predatory bugs select patches based on patch productivity rather than on prey quality or oviposition rate on a patch.
Characterizing ecosystem‐level consequences of biological invasions: the role of ecosystem engineers
Authors: Crooks Jeffrey A.
Published: March 2003

Invasions by exotic species represent both threats to ecosystems as well as opportunities to learn more about them. Among the invaders that will have the largest impacts are those that directly modify ecosystems and thus have cascading effects for resident biota. Exotics can affect ecosystems by altering system‐level flows, availability, or quality of nutrients, food, and physical resources (e.g. living space, water, heat or light). The invader‐mediated control of physical resources, typically achieved through the modification of habitats, has received limited attention in invasion biology. This reflects a general trend in ecology, and only recently has the concept of ecosystem engineering been developed to account for the role of species that shape habitats. Plants and animals in terrestrial and aquatic systems can both create and destroy structure. When introduced into ecosystems, these exotic engineers cause physical state changes with effects that ramify throughout the system. Although the consequences of these modifications are varied and complex, insight gained from general ecological principles offers an opportunity to predict what invaders will do upon their integration into systems. Examples from the literature suggest that introduced ecosystem engineers that increase habitat complexity or heterogeneity tend to cause abundances and/or species richness to rise, while those that decrease complexity tend to have the reverse effect. In assessing such patterns, however, it is critical to also consider spatial scales and the life habits of resident organisms. In addition to providing predictive power, recognition of engineering as a major means by which invasive species affect ecosystems provides a unifying theme for invasion biology and offers a chance to consider more fully the general role of species in ecosystems.
Early onset of reproductive senescence in domestic sheep Ovis aries
Authors: Mysterud Atle , Steinheim Geir , Yoccoz Nigel G. , Holand Øystein , Stenseth Nils Chr.
Published: March 2003

A central theme in life history theory is to determine how reproduction varies with age in iteroparous organisms. Evidence of ageing and senescence, defined as the progressive loss of function accompanied by decreased performance with age, remains poorly documented for large herbivores, in particular as it relates to reproduction. Analyses of body weight of 87 532 domestic sheep lambs demonstrates that onset of reproductive senescence in ewes occurs already at 5 and 6 years of age when measured, respectively, as lamb weight and litter size produced. This provides convincing evidence of early onset of reproductive senescence in this highly domesticated sheep breed. As this is earlier than indicated for other Ovis species as well as for the Soay sheep, an ancient and lightly domesticated sheep, we hypothesize that there may be a cost of selection for large litter size in mammalian herbivores.
Basins of attraction: population dynamics with two stable 4‐cycles
Authors: Henson Shandelle M. , Costantino R. F. , Desharnais Robert A. , Cushing J. M. , Dennis Brian
Published: March 2003

We use the concepts of composite maps, basins of attraction, basin switching, and saddle fly‐by's to make the ecological hypothesis of the existence of multiple attractors more accessible to experimental scrutiny. Specifically, in a periodically forced insect population growth model we identify multiple attractors, namely, two locally stable 4‐cycles. Using the model‐predicted basins of attraction, we examine data time series from a Tribolium experiment for evidence of the multiple attractors. We conclude that the multiple attractor hypothesis together with demographic stochasticity accounts for the experimental observations.
Does bird community structure vary with landscape patchiness? A Chihuahuan Desert perspective
Authors: Gutzwiller Kevin J. , Barrow, Jr. Wylie C.
Published: March 2003

During the springs of 1995–1997, we studied birds and landscapes at 70 sites in the Chihuahuan Desert to assess relations between bird community structure and landscape patchiness. Within each of two spatial extents (1‐km and 2‐km‐radius areas centered on each site), we measured the number of patches of individual land‐cover types and the total number of patches of all land‐cover types. Mean bird richness, and the mean abundance and probability of occurrence of most bird species were significantly correlated with one or more of these variables. Contrary to evidence from other systems, positive association with landscape patchiness did not increase with the degree to which species were habitat generalists, was not negatively related to body size, and did not differ between neotropical migrants and nonmigrants. For the communities’ primary constituent species as a group, the strength of positive and negative associations with patchiness did not differ between landscape extents. Within the 1‐km but not the 2‐km extent, habitat specialists were more positively and negatively associated with patchiness than were habitat generalists. In general, however, neither habitat breadth, body size, nor migratory status seemed to be responsible for associations with landscape patchiness. Mean richness, and the mean abundance and probability of occurrence of most species were significantly correlated with patchiness within one or both extents, and patchiness of all of the most extensive land‐cover types was influential. The simplest explanation for most of the bird‐patchiness relations we found is that the associations reflected species‐specific habitat needs. Through effects on avian richness, abundance, and occurrence, landscape patchiness affected bird community structure. A more complete understanding of the effects of landscape patchiness on bird community structure is likely to emerge when ecologists study the patchiness of major land‐cover types at various spatial extents.
Herbivory on Acacia seedlings in an East African savanna
Authors: Shaw Margaret T. , Keesing Felicia , Ostfeld Richard S.
Published: March 2003

Trees critically affect the functioning of savanna ecosystems through their effects on nutrient cycling, water availability, and patterns of space use by wildlife. Therefore, whatever factors influence successful recruitment of tree seedlings are important filters controlling savanna ecosystem function. In African savannas, large mammals have been considered the most important agents of mortality for adult trees, but their impacts on tree seedlings are not well‐known. Similarly, the effects of rodents and invertebrates as seedling predators are largely unstudied in Africa. To assess the relative roles of large mammals, rodents, and invertebrates as predators of Acacia seedlings in an African savanna, we conducted two experiments in which we exposed Acacia drepanolobium seedlings to different guilds of herbivores. In the first experiment, seedlings exposed to rodent and invertebrate herbivores did not suffer greater damage than did seedlings exposed only to invertebrates, suggesting that invertebrates caused most of the damage to the seedlings. In the second experiment, 63% of seedlings exposed to all herbivores (large mammals, rodents, and invertebrates) suffered major damage or mortality in 14 days. Seedlings exposed to only rodents and invertebrates, however, suffered damage at a faster rate than did seedlings exposed to rodents, invertebrates, and large mammals, suggesting that small herbivores (rodents and invertebrates) might be compensating for the removal of large herbivores. Certain specific types of damage, such as cotyledon removal, were significantly more common in areas from which large mammals had been excluded, suggesting that the invertebrate herbivore community may differ between areas with and without large mammals. Overall, invertebrates caused the greatest damage to seedlings while rodents had relatively little effect and no seedlings were consumed or trampled by large mammals. Our results indicate that invertebrates can have a pronounced influence on seedling survival for a dominant savanna tree, which in turn may influence tree recruitment and ecosystem function.
Sub‐therapeutic exposure to polyene antimycotics elicits a post‐antifungal effect (PAFE) and depresses the cell surface hydrophobicity of oral Candida albicans isolates
Authors: Egusa H. , Ellepola A. N. B. , Nikawa H. , Hamada T. , Samaranayake L. P.
Published: March 2003

Abstract: Post‐antifungal effect (PAFE) is defined as the suppression of growth that persists following limited exposure of fungi to antimycotics and subsequent removal of the drug. The fungal pathogen Candida albicans is the major aetiologic agent of oral candidosis, and the cell surface hydrophobicity (CSH) of this yeast is considered a critical factor contributing to its colonisation potential. As the concentration of topically prescribed antifungals reach sub‐therapeutic levels at dosage intervals, the study of the polyene‐induced PAFE and its impact on the CSH of oral C. albicans should be of clinical relevance. Hence the aims of this investigation were to measure the PAFE and CSH of 12 isolates of C. albicans following limited exposure (1 h) to nystatin and amphotericin B and also to investigate the ultrastructural features of yeast cells following such antifungal exposure. The yeasts were exposed to sub‐lethal concentrations of nystatin (×2 MIC) and amphotericin B (×2 MIC) for a period of 1 h. Following subsequent removal of the drug, the PAFE and the CSH of the isolates were assessed by a turbidometric measurement of growth and a biphasic aqueous‐hydrocarbon assay, respectively. The mean duration of PAFE of nystatin and amphotericin B were 5.99 (±0.49) h and 8.73 (±0.93) h, respectively, while the reduction in CSH following exposure to these drugs were 17.32% (P<0.05 for 83% of the isolates) and 14.26% (P<0.05 for 66% of the isolates), respectively. On scanning electron microscopy the exposed cells were seen to undergo collapse of the internal cell membrane, leaving an intact cell wall, while a proportion of cells were deflated. Some cells showed intense puckering of the cell wall, resulting in a mulberry appearance. Taken together, these data elucidate additional mechanisms by which polyene antimycotics may operate in vivo to suppress candidal pathogenicity.
Comparison of BrdU and cyclin A as markers of the S‐phase in oral precancerous lesions
Authors: Oliver Richard J. , MacDonald D. Gordon
Published: March 2003

Abstract: A study comparing bromodeoxyuridine (BrdU) and cyclin A as markers of cells in the S‐phase in oral precancerous lesions was performed. These were also compared with the growth fraction (GF) as assessed by Ki‐67. Biopsies of 15 lesions were obtained, presenting clinically as leukoplakia or erythroplakia of the lateral tongue or floor of mouth. Half of each biopsy was incubated in BrdU and routinely fixed and processed. Sequential sections from each block were cut and stained immunohistochemically with antibodies against the following proteins: BrdU, Ki‐67 and cyclin A. Stained sections were quantified and the labelling indices (LI) expressed per 100 of the total nucleated cell population (%) and per millimetre basement length (/mm). The mean LI% for BrdU was 11.24% (SD 2.83), for cyclin A it was 12.76% (SD 3.88) and the GF% was 29.25% (SD 11.88). The mean LI/mm for BrdU was 40.93/mm (SD 11.88), for cyclin A it was 47.59/mm (SD 18.28) and the GF/mm was 110.72/mm (SD 49.30). The BrdU and cyclin A indices were significantly correlated with each other. In the more dysplastic cases, the cyclin A LI was quantitatively much larger than that for BrdU, suggesting that the protein was being overexpressed. It was concluded that as a tool to study the kinetic aspects of the cell cycle in dysplastic lesions cyclin A was limited by the fact that it is overexpressed. In minimally dysplastic lesions and normal epithelia, however, cyclin A may be a viable alternative to BrdU for the study of the S‐phase.
DNA methylation: an epigenetic pathway to cancer and a promising target for anticancer therapy
Authors: Worm Jesper , Guldberg Per
Published: March 2003

The unique properties of a cancer cell are acquired through a stepwise accumulation of heritable changes in the information content of proto‐oncogenes and tumor suppressor genes. While gain, loss, and mutation of genetic information have long been known to contribute to tumorigenesis, it has been increasingly recognized over the past 5 years that ‘epigenetic’ mechanisms may play an equally important role. The main epigenetic modification of the human genome is methylation of cytosine residues within the context of the CpG dinucleotide. De novo methylation of ‘CpG islands’ in the promoter regions of tumor suppressor genes may lead to transcriptional silencing through a complex process involving histone deacetylation and chromatin condensation, and thus represents a tumorigenic event that is functionally equivalent to genetic changes like mutation and deletion. DNA methylation is interesting from a diagnostic viewpoint because it may be easily detected in DNA released from neoplastic and preneoplastic lesions into serum, urine or sputum, and from a therapeutic viewpoint because epigenetically silenced genes may be reactivated by inhibitors of DNA methylation and/or histone deacetylase. A better understanding of epigenetic mechanisms leading to tumor formation and chemoresistance may eventually improve current cancer treatment regimens and be instructive for a more rational use of anticancer agents.
High incidence of autoantibodies in Taiwanese patients with oral submucous fibrosis
Authors: Chiang C. P. , Hsieh R. P. , Chen T. H. H. , Chang Y. F. , Liu B. Y. , Wang J. T. , Sun A. , Kuo M. Y. P.
Published: March 2003

Background:  Previous study has shown a high incidence of autoantibodies including antinuclear (ANA), antismooth muscle (SMA), antigastric parietal cell (GPCA), antithyroid microsomal (TMA), and antireticulin antibodies in a small group of 26 patients with oral submucous fibrosis (OSF). The reasons why some of the OSF patients have high titers of autoantibodies in serum have not been completely explained and no further study on autoantibodies in OSF patients has been done in a large group of patients.

Methods:  In this study, we determined the serum levels of ANA, SMA, GPCA, and TMA in a large group of 109 male Taiwanese patients with OSF by an indirect immunofluorescence technique (for ANA, SMA, and GPCA), and by a semiquantitative microtiter particle agglutination test (for TMA). The presence of serum autoantibodies in OSF patients was further correlated with patients' oral habits and the severity of OSF measured by maximum mouth opening (MMO) and sites of involvement.

Results:  We found that the frequencies of presence of serum ANA (23.9%), SMA (23.9%), and GPCA (14.7%) in OSF patients were significantly higher than those (9.2, 7.3, and 5.5%, respectively) in healthy control subjects (P < 0.01, P < 0.005, and P < 0.05, respectively). Although the frequency of presence of TMA (5.5%) in OSF patients was also greater than that (2.8%) in healthy control subjects, the difference was not significant (P > 0.05). The presence of serum GPCA in OSF patients was significantly associated with daily areca quid (AQ) consumption (P < 0.05). The presence of serum ANA in OSF patients associated with daily AQ consumption was of borderline statistical significance (P = 0.066). However, no significant correlations were demonstrated between the presence of serum autoantibodies in OSF patients and other variables of oral habits, MMO, and sites of involvement.

Conclusion:  In this study, all the 109 OSF patients had AQ chewing habit and 73.4% of the OSF patients swallowed the ‘juice’ of AQ during the chewing process. The presence of serum GPCA and ANA in OSF patients was associated with daily consumption of AQs. AQ chewing caused mucosal microtrauma, and ulcerations facilitated the diffusion of genotoxic and cytotoxic AQ ingredients into the oral and gastric tissues. Altered autoantigens released from AQ ingredients‐damaged cells may induce autoantibody production. Higher frequencies of specific HLA‐DR antigens in OSF patients may also help autoantibody production. Therefore, we conclude that the high incidence of autoantibodies in OSF patients may be due to AQ chewing habit, toxic AQ ingredients, and genetic susceptibility of the OSF patients.
Odontogenic cyst with verrucous proliferation
Authors: Aldred Michael J , Talacko Anna A , Allan Peter G , Shear Mervyn
Published: March 2003

An unusual case of an odontogenic cyst with verrucous proliferation is described in a 13‐year‐old girl. This histologically distinctive odontogenic cyst variant does not appear to have been reported previously. The cyst was characterised by a series of verrucous projections in the lumen with hypergranulosis and cells resembling koilocytes, raising the possibility of a viral aetiology. However, no evidence of human papillomavirus (HPV) was found using immunohistochemistry and polymerase chain reaction (PCR) amplification.
Metastatic infiltration of the dental pulp by medulloblastoma
Authors: Ahmad S. , Roberts G. J. , Lucas V. S. , Barrett A. W. , Harkness W.
Published: March 2003

Medulloblastoma is an infratentorial primitive neuroectodermal tumour. It is the most commonly occurring brain tumour of childhood, accounting for 15–20% of all paediatric tumours. Extracranial metastasis is rare, but may involve the skeleton. Jaw lesions, however, have never been described. A case is reported of metastases of a medulloblastoma to the jaw including the dental pulp.
Nomenclature for Identified Pigmentation Genes in the Mouse
Authors: JORDAN SIOBHÁN , BEERMANN FRIEDRICH
Published: March 2003

More than 90 different loci influence pigmentation in the mouse. During the past few years, an increasing number of genes have been identified, and assigned to the corresponding coat color loci and pigmentation mutants. As a consequence, different names have been used in publications for loci, genes and corresponding proteins. In the following article, we present the rules and guidelines for gene nomenclature, and provide the current nomenclature for pigmentation mutants in the mouse.
Gene Correction by RNA‐DNA Oligonucleotides
Authors: ALEXEEV VITALI , YOON KYONGGEUN
Published: March 2003

An oligonucleotide composed of a contiguous stretch of RNA and DNA residues has been developed to facilitate the correction of single‐base mutations of episomal and chromosomal targets in mammalian cells. The design of the oligonucleotide exploited the highly recombinogenic RNA‐DNA hybrids and featured hairpin capped ends avoiding destruction by cellular helicases or exonucleases. The RNA‐DNA oligonucleotide (RDO) was designed to correct a point mutation in the tyrosinase gene and caused a permanent gene correction in mouse albino melanocytes, determined by clonal analysis at the level of genomic sequence, protein and phenotypic change. Recently, we demonstrated correction of the tyrosinase gene using the same RDO in vivo, as detected by dark pigmentation of several hairs and DOPA staining of hair follicles in the treated skin of albino mice. Such RDOs might hold a promise as a therapeutic method for the treatment of skin diseases. However, the frequency of gene correction varies among different cells, indicating that cellular activities, such as recombination and repair, may be important for gene conversion by RDOs. As this technology becomes more widely utilized in the scientific community, it will be important to understand the mechanism and to optimize the design of RDOs to improve their efficiency and general applicability.
Melanin Granules Prevent the Cytotoxic Effects of l‐DOPA on Retinal Pigment Epithelial Cells in Vitro by Regulation of NO and Superoxide Radicals
Authors: AKEO KIYOSHI , AMAKI SACHI , SUZUKI TAIJU , HIRAMITSU TADAHISA
Published: March 2003

Inasmuch as the nitrogen cycle elicits the direct reduction of N2 to NH3 through enzymatic reactions, and inasmuch as
l‐DOPA (
l‐dihydroxyphentlalamine), a catecholamine, can be a source of nitric oxide (NO), it is possible that melanin granules in the eye affect the generation of NO, which causes damage to the retinal pigment epithelial (RPE) cells during the oxidation of
l‐DOPA. In order to confirm this possibility, we analyzed the correlations of NO generation, cell growth, and superoxide dismutase (SOD) activities in two types (melanotic and amelanotic) of bovine RPE cells following exposure to
l‐DOPA. NO generation from
l‐DOPA was determined using an NO detector that is reliant on redox currents. The concentration of NO was measured in terms of diffusion currents run between a working electrode and a counter electrode, both being set in culture medium placed in a Petri dish. For the assays,
l‐DOPA was added to the medium at various concentrations (5, 29.9, 79.4, 152.7 or 249 μM), and 6 min after addition, an NO‐trapping agent 2,4‐carboxyphenyl‐4,4,5,5‐tetramethylimidazole‐1‐oxyl 3‐oxide (carboxy‐PTIO) was also added. The melanotic and amelanotic types of RPE cells were cultured separately in medium with
l‐DOPA under an atmosphere containing 20, 10 or 5% oxygen. Cell numbers were counted using a Coulter counter, and SOD activities were determined following incubation for 24, 48 or 72 hr using a modification of the luminol assay. The results obtained indicated that: (a) NO was produced from
l‐DOPA in a concentration‐dependent manner and was trapped quantitatively by carboxy‐PTIO; (b) the generation of NO was inhibited more markedly in the melanotic cell line than in the amelanotic one, suggesting an increased tolerance to
l‐DOPA‐derived cytotoxicity in the former; and (c) the SOD activities were more affected by oxygen concentration in the melanotic cells than in the amelanotic ones. From these results, it is concluded that melanin granules in RPE cells have a role in preventing the cytotoxicity derived from
l‐DOPA and in regulating the generation of NO and superoxide radicals.