GEOGRAPHICAL REVIEW, Issue 1 2002
THOMAS A. WIKLE
ABSTRACT. Since the early 1980s the growing popularity of cellular communication has wrought dramatic landscape changes on the American scene through an invasion of thousands of cellular telephone towers. Objections raised to new tower construction by local residents, interest groups, and regulatory boards range from visual impacts to perceived health risks. This essay traces the origins of wireless telephony, its proliferation across the United States, and the visual impacts associated with tower construction. Three stages in the geographical expansion of wireless networks are identified. [source]

DOSE-DEPENDENT EFFECT OF LUMINAL BUTYRATE ON EPITHELIAL PROLIFERATION IN THE DISTAL COLON OF RATS

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 2001
S Sengupta
Butyrate, a major product of bacterial fermentation of dietary fibre, is trophic to the colonic epithelium, when deprived of dietary fibre or faecal stream. However, the dose,response relationship of butyrate to this trophic effect is not known. The mechanism of this effect is still debated and how it relates to the antitumorigenic action of butyrate is unclear. Aim, To characterise the dose,response relationship of the effect of butyrate delivered topically to the distal colon on fibre-deprived atrophic colonic epithelium in rats. Methods, Sixty-four male Sprague,Dawley rats were maintained on a fibre-free AIN 93G diet for 3 weeks to induce mucosal atrophy in the colon. The rats then underwent laparotomy for colonic intubation, in which a polyethylene tube was positioned at the proximal end of the distal colon via a caecotomy. After recovering from surgery, they were randomly divided into five groups, which were given for 4 days twice daily infusions of 0.5 mL butyrate at doses of 0, 10, 20, 40 or 80 mm (at which complete reversal of atrophy has been previously observed). Prior to sacrifice, the rats were injected intraperitoneally with vincristine to induce mitotic arrest. Crypt column heights and mitotic arrests were quantified by light microscopy. Results, All treatment groups were healthy and stress-free. The mucosa of vehicle-infused rats was atrophic (mean 38 cells/crypt). Effects of twice daily infusions of butyrate were first observed on cell proliferation (number of mitotic arrests per crypt column) at 10 mm, and increased linearly to 80 mm. Crypt column height increased linearly from 20 mm to 80 mm, at which a mean of 45 cells/crypt were observed (the number usually observed in chow-fed healthy rats). The mitotic index (number of mitotic arrests per 100 crypt cells) also increased linearly from 10 mm. Conclusions, Butyrate's trophic effect showed a linear dose,dependent relationship. Although a maximal effect was not convincingly demonstrated, the results indicate that very small amounts of butyrate are required to affect epithelial proliferation. Since much higher luminal delivery is required to suppress tumorigenesis in this model, the mechanism by which butyrate exerts its trophic and antitumorigenic effects are likely to be different. [source]

PROLIFERATION OF ACADEMIC JOURNALS: EFFECTS ON RESEARCH QUANTITY AND QUALITY

METROECONOMICA, Issue 4 2007
Rajeev K. Goel
ABSTRACT There have been significant structural changes in research markets in recent years reflected in the increase in the number of academic journals. This paper uses a differential game model of authors and journal editors to examine the effects of an increase in competition among academic journals. Does an increase in the number of academic journals lead to an increase in scholarly articles published? Will an increase in publishing outlets adversely affect research quality? The results show greater competition does not affect research output and in fact enhances research quality. The number of journals and the relative discount rates of authors and editors are crucial determinants of the effects of competition. [source]

STIMULATION OF OESTROGEN RECEPTOR-EXPRESSING ENDOTHELIAL CELLS WITH OESTROGEN REDUCES PROLIFERATION OF COCULTURED VASCULAR SMOOTH MUSCLE CELLS

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 3 2008
Malin Odenlund
SUMMARY 1Oestrogen reduces vascular smooth muscle cell proliferation in mouse vascular injury models. Data on the antiproliferative effect of oestrogen in cultured vascular smooth muscle cells (VSMC) are less conclusive than those obtained in whole animal studies. 2In the present study, we investigated the hypothesis that oestrogen-induced attenuation of VSMC proliferation is facilitated by the presence of endothelial cells (EC) using a coculture system of EC and VSMC. 3Treatment with a physiological concentration of oestrogen (17,-estradiol (E2); 100 nmol/L) had no effect on fetal calf serum (FCS)-stimulated DNA synthesis in either A7r5 VSMC or bEnd.3 EC. However, stimulation of bEnd. 3 cells with E2 in a coculture system of bEnd.3 and A7r5 cells reduced FCS-induced DNA synthesis in A7r5 cells by approximately 45%. The nitric oxide synthase inhibitor NG -nitro- l- arginine methyl ester (l -NAME; 100 µmol/L) did not reverse the oestrogen-induced attenuation of DNA synthesis. The antiproliferative effect of E2 may be mediated via either oestrogen receptor (ER) ,, ER, or both because the bEnd.3 cells expressed immunoreactivity for both ER subtypes. 4These data show that ER,- and ER,-expressing endothelial cells, which are stimulated with a physiological concentration of oestrogen, release a factor(s) that arrests the proliferation of cocultured VSMC. Oestrogen-induced attenuation of vascular smooth muscle cell proliferation is not prevented by l -NAME, suggesting that a mechanism other than endothelial NO is involved. [source]

ISOLIQUIRITIGENIN INHIBITS THE PROLIFERATION AND INDUCES THE APOPTOSIS OF HUMAN NON-SMALL CELL LUNG CANCER A549 CELLS

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 7 2004
Ya-Ling Hsu
SUMMARY 1.,Isoliquiritigenin (ISL) is a natural pigment with the simple chalcone structure 4,2,,4,-trihydroxychalcone. In the present study, we report, for the first time, ISL-induced inhibition of the proliferation of the human non-small cell lung cancer A549 cell line. 2.,The results showed that ISL not only inhibited A549 cell proliferation, but also induced apoptosis and blocked cell cycle progression in the G1 phase. An ELISA assay demonstrated that ISL significantly increased the expression of p53 and p21/WAF1 protein, which caused cell cycle arrest. 3.,An enhancement in Fas and its two ligands, namely membrane-bound Fas ligand (mFasL) and soluble Fas ligand (sFasL), may be responsible for the apoptotic effect induced by ISL. 4.,Taken together, the results indicate that the p53 and Fas/FasL apoptotic system may participate in the antiproliferative activity of ISL in A549 cells. [source]

BS14 UPDATE ON IN SITU PROLIFERATIONS OF THE BREAST

ANZ JOURNAL OF SURGERY, Issue 2007
G. C. Harris
This is a pathologist's view of in situ proliferations of the breast, particularly those other than DCIS. The increasing evidence for Lobular Carcinoma In Situ (LCIS) as a non-obligate precursor, at least in some instances, and the emerging entity of pleomorphic LCIS will be discussed. Columnar cell proliferations including Flat Epithelial Atypia will also be presented with particular emphasis on clinical significance and currently recommended management strategies. A short discussion of other "indeterminate" in situ proliferations will also be included. [source]

Proliferation as More and Other to Mutuality and Synthesis Within Curriculum Studies: A Response to Hlebowitsh

CURRICULUM INQUIRY, Issue 4 2010
ERIK MALEWSKI
First page of article [source]

Proliferation and differentiation of intestinal stem cells during metamorphosis of the red flour beetle, Tribolium castaneum

DEVELOPMENTAL DYNAMICS, Issue 4 2008
R. Parthasarathy
Abstract The insect midgut epithelium is remodeled during larval-pupal metamorphosis when larval polyploid cells (LPCs) are replaced by the daughters of intestinal stem cells (ISCs). We characterized the proliferation of ISCs during midgut remodeling in the red flour beetle, Tribolium castaneum. Midgut remodeling is initiated at 96 hr after ecdysis into the final instar larval stage. Immunocytochemistry with bromodeoxyuridine and phospho-histone H3 antibodies showed that the ISCs are the progenitors of the pupal/adult midgut epithelium and they undergo proliferation and differentiation to form new midgut epithelium. In vitro midgut culture experiments revealed that 20-hydroxyecdysone (20E) in the absence of juvenile hormone induces proliferation of ISCs. RNA interference (RNAi) mediated silencing of ecdysone receptors (EcRA and EcRB) and ultraspiracle (USP) identified EcRA and USP but not EcRB as the proteins involved in 20E regulation of ISCs proliferation. These data show that the proliferation of ISCs is under both developmental and endocrine regulation. Developmental Dynamics 237:893,908, 2008. © 2008 Wiley-Liss, Inc. [source]

Cell proliferation during blastema formation in the regenerating teleost fin

DEVELOPMENTAL DYNAMICS, Issue 2 2002
Leonor Santos-Ruiz
Abstract Epimorphic regeneration in teleost fins occurs through the establishment of a balanced growth state in which a blastema gives rise to all the mesenchymal cells, whereas definite areas of the epidermis proliferate leading to its extension, thus, allowing the enlargement of the whole structure. This type of regeneration involves specific mechanisms that temporally and spatially regulate cell proliferation. To understand how the blastema is formed and how this growth situation is set up, we investigated cell proliferation patterns in the regenerating fin of the goldfish Carassius auratus from the time of amputation to that of blastema formation by using proliferating cell nuclear antigen immunostaining and bromodeoxyuridine labeling. Wound closure and apical epidermal cap formation took place by epidermal migration and re-arrangement, without the contribution of cell proliferation. As soon as the apical cap had formed, the epidermis started to proliferate at its lateral surfaces, in which all layers maintained cycling for the duration of the studied process. The distal epidermal cap, on the contrary, presented very few cycling cells, and its cytoarchitecture was indicative of continuous remodeling due to ray growth. The basal layer of this epidermal cap showed a typical morphology and remained nonproliferative whilst in contact with the proliferating blastema. Proliferation in the mesenchymal compartment of the ray started far from the amputation plane. Subsequently, cycling cells approached that location, until they formed the blastema in contact with the apical epidermal cap. Differences observed between the epidermis and mesenchyma, regarding activation of the cell cycle and the establishment of proliferative patterns, suggest that differential mechanisms regulate cell proliferation in each of these compartments during the initial stages of regeneration. © 2002 Wiley-Liss, Inc. [source]

Adult neurogenesis in the crayfish brain: Proliferation, migration, and possible origin of precursor cells

DEVELOPMENTAL NEUROBIOLOGY, Issue 7 2009
Yi Zhang
Abstract The birth of new neurons and their incorporation into functional circuits in the adult brain is a characteristic of many vertebrate and invertebrate organisms, including decapod crustaceans. Precursor cells maintaining life-long proliferation in the brains of crayfish (Procambarus clarkii, Cherax destructor) and clawed lobsters (Homarus americanus) reside within a specialized niche on the ventral surface of the brain; their daughters migrate to two proliferation zones along a stream formed by processes of the niche precursors. Here they divide again, finally producing interneurons in the olfactory pathway. The present studies in P. clarkii explore (1) differential proliferative activity among the niche precursor cells with growth and aging, (2) morphological characteristics of cells in the niche and migratory streams, and (3) aspects of the cell cycle in this lineage. Morphologically symmetrical divisions of neuronal precursor cells were observed in the niche near where the migratory streams emerge, as well as in the streams and proliferation zones. The nuclei of migrating cells elongate and undergo shape changes consistent with nucleokinetic movement. LIS1, a highly conserved dynein-binding protein, is expressed in cells in the migratory stream and neurogenic niche, implicating this protein in the translocation of crustacean brain neuronal precursor cells. Symmetrical divisions of the niche precursors and migration of both daughters raised the question of how the niche precursor pool is replenished. We present here preliminary evidence for an association between vascular cells and the niche precursors, which may relate to the life-long growth and maintenance of the crustacean neurogenic niche. © 2009 Wiley Periodicals, Inc. Develop Neurobiol, 2009 [source]

Proliferation patterns of cervical cells as visualized in Leiden liquid cytology slides

DIAGNOSTIC CYTOPATHOLOGY, Issue 1 2004
Laura Luzzatto M.D.
Abstract The Leiden liquid-based cytology method for the preparation of optimal cytological slides is reported. In such slides, the proliferation pattern of cervical cells can be visualized in detail. Cervical smears and suspension preparations of 665 consecutive unselected patients received in 2003 were studied. Of the 665 patients, 26 (10 normal, 10 with cervical atrophy, 5 with mild dysplasia, and 1 carcinoma in situ) were selected. After using the Thermo Shandon Papspin, the wet slides were placed on a hot plate and dried for 30 min. Proliferation of the cervical cells was visualized in brown by staining the cells for MiB-1 antigen, and nuclear DNA in blue by a standardized short staining with hematoxylin. We found excellent high-resolution demonstrability of cell cycle-related MiB-1 distribution in the well-flattened nuclei. The phase of the cell cycle could be deduced from brown-blue staining patterns. There was a significant increase of MiB-1-positive cell yield related to progression in the degree of pathology. Diagn. Cytopathol. 2004;31:5,9. © 2004 Wiley-Liss, Inc. [source]

Mechanisms of Epileptogenesis in Tuberous Sclerosis Complex and Related Malformations of Cortical Development with Abnormal Glioneuronal Proliferation

EPILEPSIA, Issue 1 2008
Michael Wong
Summary Malformations of cortical development (MCDs) are increasingly recognized as causes of medically intractable epilepsy. In order to develop more effective, rational therapies for refractory epilepsy related to MCDs, it is important to achieve a better understanding of the underlying mechanisms of epileptogenesis, but this is complicated by the wide variety of different radiographic, histopathological, and molecular features of these disorders. A subset of MCDs share a number of characteristic cellular and molecular abnormalities due to early defects in neuronal and glial proliferation and differentiation and have a particularly high incidence of epilepsy, suggesting that this category of MCDs with abnormal glioneuronal proliferation may also share a common set of primary mechanisms of epileptogenesis. This review critically analyzes both clinical and basic science evidence for overlapping mechanisms of epileptogenesis in this group of disorders, focusing on tuberous sclerosis complex, focal cortical dysplasia with balloon cells, and gangliogliomas. Specifically, the role of lesional versus perilesional regions, circuit versus cellular/molecular defects, and nonneuronal factors, such as astrocytes, in contributing to epileptogenesis in these MCDs is examined. An improved understanding of these various factors involved in epileptogenesis has direct clinical implications for optimizing current treatments or developing novel therapeutic approaches for epilepsy in these disorders. [source]

Transcription factor Fli-1 expression by bone marrow cells in chronic myeloproliferative disorders is independent of an underlying JAK2 (V617F) mutation

EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2006
Oliver Bock
Abstract:,Objectives:,Friend leukemia integration-1 (Fli-1), a member of the Ets gene family of transcription factors, has been demonstrated to be a target of a leukaemia inducing virus in mice, and is known to be part of a fusion gene in Ewings' sarcoma in humans. Wild-type Fli-1 is involved in lineage commitment of megakaryocytes and myeloid progenitors through induction of Janus kinases (JAKs) following ligand binding to cytokine and growth factor receptors. Proliferation of atypical megakaryocytes is a predominant histopathological feature in Philadelphia chromosome negative chronic myeloproliferative disorders (Ph, CMPD) and a potential aberrant expression of Fli-1 has not been investigated so far. Methods:,Fli-1 expression was investigated by real-time RT-PCR and immunohistochemistry in bone marrow cells derived from Ph, CMPD (n = 80) and non-neoplastic haematopoiesis (n = 21) following determination of the JAK2 status. Results:,Fli-1 mRNA expression was significantly higher in Essential thrombocythaemia (ET) with JAK2 (V617F) compared with other Ph, CMPD and control (P < 0.001). By immunohistochemistry, Fli-1 protein could be detected in nuclei of atypical megakaryocytes in Ph, CMPD and, less accentuated, in non-neoplastic megakaryocytes. Fli-1 protein expression by myeloid progenitors was considerably heterogenous in Ph, CMPD independent of an underlying JAK2 (V617F) mutation and without notable differences to non-neoplastic haematopoiesis. Conclusion:,Fli-1 is rather constitutively expressed by bone marrow cells in Ph, CMPD independent of the underlying JAK2 status. The overall stronger labelling for Fli-1 in megakaryocytes in Ph, CMPD most likely reflects the degree of polyploidisation but aberrant activation of nuclear target genes can not be excluded. [source]

Dendritic cells derived from TBP-2-deficient mice are defective in inducing T cell responses

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 5 2008
Aoi Son
Abstract Thioredoxin-binding protein-2 (TBP-2), also known as vitamin,D3-up-regulated protein,1 (VDUP1), was identified as an endogenous molecule interacting with thioredoxin (TRX). Here, we show that dendritic cells (DC) derived from TBP-2-deficient mice are defective in the function of T cell activation. To compare TBP-2,/, DC function with wild-type (WT) DC, we stimulated DC with lipopolysaccharide (LPS). Although TBP-2,/, DC and WT DC expressed comparable levels of MHC class,II and costimulatory molecules such as CD40, CD80 and CD86, the IL-12p40, IL-12p70 and IL-6 productions of TBP-2,/, DC were attenuated. In a mixed leukocyte reaction (MLR), the concentrations of IL-2, IFN-,, IL-4 and IL-10 in the culture supernatant of MLR with TBP-2,/, DC were significantly lower than those in the cultures with WT DC. In MLR also, as with LPS stimulation, IL-12p40 and IL-12p70 production from TBP-2,/, DC was less than that from WT DC. Proliferation of T cells cultured with TBP-2,/, DC was poorer than that with WT DC. Invivo delayed-type hypersensitivity responses in TBP-2,/, mice immunized with ovalbumin were significantly reduced compared to WT mice. These results indicate that TBP-2 plays a crucial role in DC to induce T cell responses. [source]

Proliferation and interleukin,5 production by CD8hiCD57+ T cells

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 4 2008

Abstract CD8hiCD57+ T cells have previously been described as effector memory T cells with minimal expansion capacity and high susceptibility to activation-induced cell death. In contrast, we demonstrate here that CD8hiCD57+ T cells are capable of rapid expansion using multiple techniques including [3H]thymidine uptake, flow cytometric bead-based enumeration and standard haemocytometer counting. Previous reports can be explained by marked inhibition of activation-induced expansion and increased 7-amino-actinomycin,D uptake by CD8hiCD57+ T cells following treatment with CFSE, a dye previously used to measure their proliferation, combined with specific media requirements for the growth of this cell subset. The ability of CD8hiCD57+ T cells to further differentiate is highlighted by a distinct cytokine profile late after activation that includes the unexpected release of high levels of interleukin,5. These data indicate that CD8hiCD57+ T cells should not be considered as "end-stage" effector T cells incapable of proliferation, but represent a highly differentiated subset capable of rapid division and exhibiting novel functions separate from their previously described cytotoxic and IFN-, responses. [source]

The ratio between dendritic cells and T,cells determines the outcome of their encounter: Proliferation versus deletion

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 10 2005

Abstract Dendritic cells (DC) either induce T,cell tolerance or contribute to the initiation and modulation of T and B,cell responses. Since many of the variables determining the thresholds of naive T,cell priming were defined in vitro using a homogeneously matured DC population, we here focused on partially mature DC which might reflect the occurrence of tumor-infiltrating and thymic DC. To predict how those DC regulate the induction of antigen-specific T,cell proliferation and T,cell tolerance, we co-cultured ovalbumin-pulsed murine DC at different ratios with antigen-specific DO11.10 transgenic T,cells. Whereas partially mature DC at a DC/T,cell ratio of 1,:,10 supported proliferation, a DC/T,cell ratio of 1,:,2 induced proliferation arrest in naive CD4+ T,cells. The acquisition of the NK cell inhibitory markers NK1.1 and KLRG on T,cells exposed to high numbers of DC suggests a role for these molecules in the protection of antigen-responsive T,cells from exhaustion by overstimulation. Mechanistically, abortive T,cell proliferation upon encounter of high numbers of partially mature DC is caused by an apoptosis-related pathway, suggesting that excessive antigen density without sufficient costimulation results in activation-induced cell death. [source]

Pathogenesis of Lyme neuroborreliosis: Borrelia burgdorferi lipoproteins induce both proliferation and apoptosis in rhesus monkey astrocytes

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 9 2003
Geeta Ramesh
Abstract Brain invasion by Borrelia burgdorferi, the agent of Lyme disease, results in an inflammatory and neurodegenerative disorder called neuroborreliosis. In humans, neuroborreliosis has been correlated with enhanced concentration of glial fibrillary acidic protein in the cerebrospinal fluid, a sign of astrogliosis. Rhesus monkeys infected by us with B.,burgdorferi showed evidence of astrogliosis, namely astrocyte proliferation and apoptosis. We formulated the hypothesis that astrogliosis could be caused by spirochetal lipoproteins. We established primary cultures of rhesus monkey astrocytes and stimulated the cells with recombinant lipidated outer surface protein,A (L-OspA), a model B.,burgdorferi lipoprotein, and tripalmitoyl-S-glyceryl-Cys-Ser-Lys4 -OH (Pam3Cys), a synthetic lipopeptide that mimics the structure of the lipoprotein lipid moiety. L-OspA elicited not only astrocyte proliferation but also apoptosis, two features observed during astrogliosis. Astrocytes produced both IL-6 and TNF-, in response to L-OspA and Pam3Cys. Proliferation induced by L-OspA was diminished in the presence of an excess of anti-IL-6 antibody, and apoptosis induced by this lipoprotein was completely suppressed with anti-TNF-, antibody. Hence, IL-6 contributes to, and TNF-, determines, astrocyte proliferation and apoptosis, respectively, as elicited by lipoproteins. Our results provide proof of the principle that spirochetal lipoproteins could be key virulence factors in Lyme neuroborreliosis, and that astrogliosis might contribute to neuroborreliosis pathogenesis. [source]

AQP4 expression in striatal primary cultures is regulated by dopamine , implications for proliferation of astrocytes

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2008
Eva Küppers
Abstract Proliferation of astrocytes plays an essential role during ontogeny and in the adult brain, where it occurs following trauma and in inflammation and neurodegenerative diseases as well as in normal, healthy mammals. The cellular mechanisms underlying glial proliferation remain poorly understood. As dopamine is known to modulate proliferation in different cell populations, we investigated the effects of dopamine on the proliferation of striatal astrocytes in vitro. We found that dopamine reduced proliferation. As proliferation involves, among other things, a change in cell volume, which normally comes with water movement across the membrane, water channels might represent a molecular target of the dopamine effect. Therefore we studied the effect of dopamine on aquaporin 4 (AQP4) expression, the main aquaporin subtype expressed in glial cells, and observed a down-regulation of the AQP4-M23 isoform. This down-regulation was the cause of the dopamine-induced decrease in proliferation as knockdown of AQP4 using siRNA techniques mimicked the effects of dopamine on proliferation. Furthermore, stimulation of glial proliferation by basic fibroblast growth factor was also abolished by knocking down AQP4. In addition, blocking of AQP4 with 10 ,m tetraethylammonium inhibited osmotically induced cell swelling and stimulation of glial cell proliferation by basic fibroblast growth factor. These results demonstrate a clear-cut involvement of AQP4 in the regulation of proliferation and implicate that modulation of AQP4 could be used therapeutically in the treatment of neurodegenerative diseases as well as in the regulation of reactive astrogliosis by preventing or reducing the glia scar formation, thus improving regeneration following ischemia or other trauma. [source]

Differences in Local Environment Determine the Site of Physiological Angiogenesis in Rat Skeletal Muscle

EXPERIMENTAL PHYSIOLOGY, Issue 5 2003
I. Badr
The specificity in location of angiogenesis to either glycolytic or oxidative fibre types, or muscle regions, was examined in the tibialis anterior (TA) and extensor digitorum longus (EDL) muscles of rat. Angiogenesis was induced by mechanical means either with (chronic muscle stimulation) or without (muscle stretch by overload) changes in blood flow, treatments which invoked only minor changes in fibre type and fibre size. Proliferation estimated by PCNA labelling of cells co-localised with capillaries was very rare in control muscles, where it occurred mainly in the glycolytic regions, but was increased in both models of angiogenesis. However, when labelled capillaries were scored according to the type of surrounding fibres, only muscle stimulation significantly accentuated proliferation of capillaries surrounded by glycolytic fibres. We conclude that while mechanical stimuli are important for proliferation in glycolytic regions in both models, capillary growth occurs specifically around glycolytic fibres in that region when the angiogenic stimulus includes increased blood flow and/or increased metabolic demand. [source]

Dehydroepiandrosterone inhibits the proliferation and induces the death of HPV-positive and HPV-negative cervical cancer cells through an androgen- and estrogen-receptor independent mechanism

FEBS JOURNAL, Issue 19 2009
Roma A. Girón
Dehydroepiandrosterone (DHEA) has a protective role against epithelial-derived carcinomas; however, the mechanisms remain unknown. We determined the effect of DHEA on cell proliferation, the cell cycle and cell death in three cell lines derived from human uterine cervical cancers infected or not with human papilloma virus (HPV). We also determined whether DHEA effects are mediated by estrogen and androgen receptors. Proliferation of C33A (HPV-negative), CASKI (HPV16-positive) and HeLa (HPV18-positive) cells was evaluated by violet crystal staining and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) reduction. Flow cytometry was used to evaluate the phases of the cell cycle, and cell death was detected using a commercially available carboxyfluorescein apoptosis detection kit that determines caspase activation. DNA fragmentation was determined using the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. Flutamide and ICI 182,780 were used to inhibit androgen and estrogen receptors, respectively, and letrozol was used to inhibit the conversion of DHEA to estradiol. Our results show that DHEA inhibited cell proliferation in a dose-dependent manner in the three cell lines; the DHEA IC50 doses were 50, 60 and 70 ,m for C33A, CASKI and HeLa cells, respectively. The antiproliferative effect was not abrogated by inhibitors of androgen and estrogen receptors or by an inhibitor of the conversion of testosterone to estradiol, and this effect was associated with an increase in necrotic cell death in HPV-negative cells and apoptosis in HPV-positive cells. These results suggest that DHEA strongly inhibits the proliferation of cervical cancer cells, but its effect is not mediated by androgen or estrogen receptor pathways. DHEA could therefore be used as an alternative in the treatment of cervical cancer. [source]

Secreted CREG inhibits cell proliferation mediated by mannose 6-phosphate/insulin-like growth factor II receptor in NIH3T3 fibroblasts

GENES TO CELLS, Issue 9 2008
Ya-Ling Han
Cellular repressor of E1A-stimulated genes (CREG) is a recently described glycoprotein that plays a critical role in keeping cells or tissues in mature, homeostatic states. To understand the relationship between CREG and its membrane receptor, mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGF2R), we first generated stable NIH3T3 fibroblasts by transfection of pDS_shCREGs vectors, which produced an approximately 80% decrease in CREG levels both in the lysate and in the media. We used fluorescence activated cell sorting and a bromide deoxyuridine incorporation assay to identify whether CREG knockdown promoted the cell proliferation associated with the increase of IGF-II in NIH3T3 fibroblasts. Proliferation was markedly inhibited in a concentration-dependent manner by re-addition of recombinant CREG protein into the media, and this was mediated by the membrane receptor M6P/IGF2R. We subsequently confirmed the direct interaction of CREG and M6P/IGF2R by both immunoprecipitation-Western blotting and immunofluorescence staining. We found that expression of CREG correlated with localization of the receptor in NIH3T3 fibroblasts but did not affect its expression. Our findings indicated that CREG might act as a functional regulator of M6P/IGF2R to facilitate binding and trafficking of IGF-II endocytosis, leading to growth inhibition. [source]

Serum and forskolin cooperate to promote G1 progression in Schwann cells by differentially regulating cyclin D1, cyclin E1, and p27Kip expression

GLIA, Issue 16 2007
Jared Iacovelli
Abstract Proliferation of Schwann cells in vitro, unlike most mammalian cells, is not induced by serum alone but additionally requires cAMP elevation and mitogenic stimulation. How these agents cooperate to promote progression through the G1 phase of the cell cycle is unclear. We studied the integrative effects of these compounds on receptor-mediated signaling pathways and regulators of G1 progression. We show that serum alone induces strong cyclical expression of cyclin D1 and E1, 6 and 12 h after addition, respectively. Serum also promotes strong but transient erbB2, ERK, and Akt phosphorylation, but Schwann cells remain arrested in G1 due to high levels of the inhibitor, p27Kip. Forskolin with serum promotes G1 progression in 22% of Schwann cells between 18 and 24 h by inducing a steady decline in p27Kip levels that reaches a nadir at 12 h coinciding with peak cyclin E1 expression. Forskolin also delays neuregulin-induced loss of erbB2 receptors allowing strong acute activation of PI3K, sustained erbB2 phosphorylation and G1 progression in 31% of Schwann cells. We find that the ability of forskolin to decrease p27Kip is associated with its ability to decrease Krox-20 expression that is induced by serum and further increased by neuregulin. Our results explain why serum is required but insufficient to stimulate proliferation and identify two routes by which forskolin promotes proliferation in the presence of serum and neuregulin. These findings provide insights into how G1 progression and, cell cycle arrest leading to myelination are regulated in Schwann cells. © 2007 Wiley-Liss, Inc. [source]

Proliferation of progenitor cells in the adult rat brain correlates with the presence of vimentin-expressing astrocytes

GLIA, Issue 4 2001
Gérard Alonso
Abstract It is well established that proliferation of progenitor cells persists within the hippocampal dentate gyrus (DG) and the subventricular zone of the lateral ventricle (SVZ) in the adult brain. The aim of the present study was to determine whether the rate of cell proliferation within these germinative zones could be correlated to the occurrence of a particular glial environment. The cell proliferation marker bromodeoxyuridine (BrdU) was administrated to rats under different physiological and experimental conditions known to modify the rate of progenitor cell proliferation. Within both germinative zones, BrdU-labeled nuclei were associated with cell bodies immunostained for the neuronal marker polysialylated neural cell adhesion molecule, but not for the glial markers glial fibrillary acidic protein (GFAP) or vimentin (VIM). In all the rats examined, however, proliferating (BrdU-labeled) cells always exhibited close relationships with immature-like astrocytes that expressed both GFAP and VIM. There was a dramatic decrease of cell proliferation in the DG from both the aged rats and the corticosterone-treated adult rats that was correlated with a decreased expression of vimentin by the astrocytes present in this region. In contrast, both cell proliferation and vimentin expression were only slightly affected in the SVZ from these two treatment groups. Conversely, after either adrenalectomy or a surgical lesion through the lateral hippocampus, the increase in cell proliferation observed in the DG was correlated to the occurrence of an increased number of GFAP and VIM double immunostained structures in these regions. All together, these data suggest that immature-like astrocytes present in the germinative zones may provide a microenvironment involved in sustaining the proliferation of progenitor cells. GLIA 34:253,266, 2001. © 2001 Wiley-Liss, Inc. [source]

Statistical Model of the Interactions Between Helicobacter pylori Infection and Gastric Cancer Development

HELICOBACTER, Issue 1 2003
Martin Welin
ABSTRACT Background. The bacterium Helicobacter pylori is associated with a number of gastrointestinal diseases, such as gastric ulcer, duodenal ulcer and gastric cancer. Several histological changes may be observed during the course of infection; some may influence the progression towards cancer. The aim of this study was to build a statistical model to discover direct interactions between H. pylori and different precancerous changes of the gastric mucosa, and in what order and to what degree those may influence the development of the intestinal type of gastric cancer. Methods. To find direct and indirect interactions between H. pylori and different histological variables, log-linear analyses were used on a case,control study. To generate mathematically and biologically relevant statistical models, a designed algorithm and observed frequency tables were used. Results. The results show that patients with H. pylori infection need to present with proliferation and intestinal metaplasia to develop gastric cancer of the intestinal type. Proliferation and intestinal metaplasia interacted with the variables atrophy and foveolar hyperplasia. Intestinal metaplasia was the only variable with direct interaction with gastric cancer. Gender had no effect on the variables examined. Conclusion. The direct interactions observed in the final statistical model between H. pylori, changes of the mucosa and gastric cancer strengthens and supports previous theories about the progression towards gastric cancer. The results suggest that gastric cancer of the intestinal type may develop from H. pylori infection, proliferation and intestinal metaplasia, while atrophy and foveolar hyperplasia interplay with the other histological variables in the disease process. [source]

Inhibition of hepatic stellate cell proliferation and activation by the semisynthetic analogue of fumagillin TNP-470 in rats

HEPATOLOGY, Issue 5 2000
Yan Qing Wang
Proliferation and activation of hepatic stellate cells (HSCs) are critical steps for the development of postnecrotic fibrosis in the liver. The present study aimed to reveal the inhibitory effect of the semisynthetic analogue of fumagillin TNP-470 on these events for its possible use as an antifibrogenic agent. Rat models of carbon tetrachloride (CCl4)- and dimethylnitrosamine-induced hepatic fibrosis were used for an in vivo study. In both models, the fibrotic area was considerably decreased by concurrent repetitive subcutaneous injections of 30 mg/kg body weight of TNP-470. In CCl4 -induced fibrosis, factor VIII-related antigen-positive blood vessels, desmin-, or ,-smooth muscle actin (,SMA)-positive mesenchymal cells, bromodeoxyuridine (BrdU)-positive mesenchymal cells also decreased in number by treatment with TNP-470. In in vitro experiments, a supplement of 1,000 ng/mL TNP-470 suppressed BrdU incorporation and cyclins D1, D2, and E expression by cultured HSCs in the absence and/or presence of platelet-derived growth factor (PDGF). Expression of HSC activation markers, i.e., ,SMA and PDGF receptor ,, was also suppressed. The present results indicate that TNP-470 inhibits HSC proliferation by blocking the cell-cycle transition from G1 to S and HSC activation, and, as the consequence, prevents the progression of hepatic fibrosis, probably being coupled with its antiangiogenic effect. [source]

Divide and conquer: the importance of cell division in regulating B-cell responses

IMMUNOLOGY, Issue 4 2004
Stuart G. Tangye
Summary Proliferation is an essential characteristic of clonal selection and is required for the expansion of antigen reactive clones leading to the development of antibody of different isotypes and memory cells. New data for mouse and human B cells point to an important role for division in regulating isotype class and in optimizing development of protective immunity by the regulated entry of cells to the plasma cell lineage. [source]

Cell Proliferation of Human Fibroblasts on Alumina and Hydroxyapatite-Based Ceramics with Different Surface Treatments,

INTERNATIONAL JOURNAL OF APPLIED CERAMIC TECHNOLOGY, Issue 2 2010
Juliana Marchi
Biocompatibility is an important characteristic of dental implant material, and in vitro tests are required to elucidate the interaction between these materials and human tissues. Cell proliferation assays were done with fibroblasts plated on the surface of alumina and hydroxyapatite sintered samples, each with a different surface treatment (sintered, rectified, or polished). After 1, 2, and three days, the samples were prepared for scanning electron microscopy observations. The data were compared by analysis of variance followed by Tukey's test. It was concluded that neither the hydroxyapatite or alumina substrate is cytotoxic, and hydroxyapatite is more biocompatible than alumina. [source]

Protein kinase B modulates the sensitivity of human neuroblastoma cells to insulin-like growth factor receptor inhibition

INTERNATIONAL JOURNAL OF CANCER, Issue 11 2006
Ana S. Guerreiro
Abstract The potential of the novel insulin-like growth factor receptor (IGF-IR) inhibitor NVP-AEW541 as an antiproliferative agent in human neuroblastoma was investigated. Proliferation of a panel of neuroblastoma cell lines was inhibited by NVP-AEW541 with IC50 values ranging from 0.15 to 5 ,M. Experiments using an IGF-IR neutralizing antibody confirmed that the IGF-IR was essential to support growth of neuroblastoma cell lines. The expression levels of the IGF-IR in individual neuroblastoma cell lines did not correlate with the sensitivities to NVP-AEW541, while coexpression of the IGF-IR and the insulin receptor (IR) correlated with lower sensitivity to the inhibitor in some cell lines. Intriguingly, high levels of activation of Akt/protein kinase B (PKB) and phosphorylation of the ribosomal S6 protein were observed in neuroblastoma cell lines with decreased sensitivities to NVP-AEW541. Inhibition of Akt/PKB activity restored the sensitivity of neuroblastoma cells to the IGF-IR inhibitor. Transfection of neuroblastoma cells with activated Akt or ribosomal protein S6 kinase (S6K) decreased the sensitivity of the cells to NVP-AEW541. IGF-I-stimulated proliferation of neuroblastoma cell lines was completely blocked by NVP-AEW541, or by a combination of an inhibitor of phosphoinositide 3-kinase and rapamycin. In addition to its antiproliferative effects, NVP-AEW541 sensitized neuroblastoma cells to cisplatin-induced apoptosis. Together, our data demonstrate that NVP-AEW541 in combination with Akt/PKB inhibitors or chemotherapeutic agents may represent a novel approach to target human neuroblastoma cell proliferation. © 2006 Wiley-Liss, Inc. [source]

Peripheral blood mononuclear cells proliferation and Th1/Th2 cytokine production in response to streptococcal M protein in psoriatic patients

INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 5 2006
Rolando Pérez-Lorenzo
Background, Psoriasis is a chronic skin disease that is probably a T cell-mediated autoimmune condition which is strongly associated with streptococcal throat infections. Although some groups have associated the involved response with different streptococcal antigens, M protein has been described as the major virulence factor of Streptococcus pyogenes. Thus, it is necessary to describe some features of the cellular responses to this streptococcal antigen. Methods, Proliferation and Th1/Th2 cytokine production of peripheral blood mononuclear cells (PBMC) in response to total soluble extracts from type M5 S. pyogenes with (TSE37Sp) and without (M,TSESp) M protein were analyzed in 10 psoriatic patients and 10 healthy controls. Results, PBMC from both patients and controls proliferated to both extracts. Responses to M,TSESp were significantly lower than those to TSE37Sp (P < 0.05). PBMC IL-2 and ,IFN production after TSE37Sp stimulus was much higher than after M,TSESp antigenic stimulation in both groups (P < 0.05). Meanwhile, IL-4 production was quite low in both groups and in response to both extracts. We found a differential production of IL-10 between groups. PBMC from healthy controls responded to TSE37Sp with a much higher production of this cytokine as compared to the responses showed to M,TSESp while the cells from psoriatic patients responded without differences in the production of IL-10. Conclusion, Results obtained suggest an important Th1 response to M protein in psoriatic patients which could be associated with the cellular responses involved in psoriasis, while healthy subjects respond in a probably non-Th2 IL-10 producing regulatory T cells fashion. [source]

Cranial fasciitis of childhood

INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 2 2003
Margarita Larralde MD
A 2-month-old boy was seen at our pediatric dermatology department with a history of a tumoral lesion of the scalp since his birth. On examination he had a single, ovoid, firm, 2 × 1.8-cm painless subcutaneous mass on the temporal left calvarium, covered by normal skin (Fig. 1). It had experienced explosive growth in the preceding 2 weeks. There was no history of previous trauma in the area. The remainder of the examination was normal. Roentgenographic studies of the skull revealed a soft-tissue mass without involvement of the underlying bone. Ultrasonography of the lesion showed it to be an echolucid tumor. With the presumed diagnosis of dermoid cyst we sent the patient for surgical removal. At surgery, the lesion did not have the typical surgical appearance of a cyst. The histopathologic exam of the specimen was interpreted as cranial fasciitis of childhood (Fig. 2). Immunohistochemistry showed diffuse positivity for vimentin and muscle actin. After 1 year the patient is free of lesions. Figure 1. Lesion at the temporal left calvarium Figure 2. Proliferation of loosely arranged spindle cells in a loose myxoid stroma (H&E stain, × 40) [source]