Total Spontaneous Regression of a Central Giant Cell Granuloma After Incisional Biopsy: A Four-Year Follow-Up Case Report

Central giant cell granuloma (CGCG) of the jaws represents a localized and benign neoplastic lesion sometimes characterized by aggressive osteolytic proliferation. The World Health Organization defines it as an intraosseous lesion composed of cellular and dense connective tissues that contain multiple hemorrhagic foci, an aggregation of multinucleated giant cells, and occasional bone tissue trabeculae. The origin of this lesion is uncertain; however, factors such as local trauma, inflammation, intraosseous hemorrhage, and genetic abnormalities have been identified as possible causes. CGCG generally affects those younger than 30 years and occurs more frequently in women (2: 1). This lesion corresponds to approximately 7% of all benign tumors of the jaws, with prevalence in the anterior region of the jaw. Aggressive lesions are characterized by symptoms, such as pain, numbness, rapid growth, cortical perforation, root resorption, and a high recurrence rate after curettage. In contrast, nonaggressive CGCGs have a slow rate of growth, may contain sparse trabeculation, and are less likely to move teeth or cause root resorption or cortical perforation. Nonaggressive CGCGs are generally asymptomatic lesions and thus are frequently found on routine dental radiographs. Radiographically, the 2 forms of CGCG present as radiolucent, expansive, unilocular or multilocular masses with well-defined margins. The histopathology of CGCG is characterized by multinucleated giant cells, surrounded by round, oval, and spindle-shaped mononuclear cells, scattered in dense connective tissue with hemorrhagic and abundant vascularization foci. The final diagnosis is determined by histopathologic analysis of the biopsy specimen. The preferred treatment for CGCG consists of excisional biopsy, curettage with a safety margin, and partial or total resection of the affected bone. Conservative treatments include local injections of steroids, calcitonin, and antiangiogenic therapy. Drug treatment using antibiotics, painkillers, and corticosteroids and clinical and radiographic monitoring are necessary for approximately 10 days after surgery. There are only a few cases of spontaneous CGCG regression described in the literature; therefore, a detailed case report of CGCG regression in a 12-yearold boy with a 4-year follow-up is presented and compared with previous studies. (c) 2014 American Association of Oral and Maxillofacial Surgeons

Differential Expression of ADAM23, CDKN2A (P16), MMP14 and VIM Associated with Giant Cell Tumor of Bone

Though benign, giant cell tumor of bone (GCTB) can become aggressive and can exhibit a high mitotic rate, necrosis and rarely vascular invasion and metastasis. GCTB has unique histologic characteristics, a high rate of multinucleated cells, a variable and unpredictable growth potential and uncertain biological behavior. In this study, we sought to identify genes differentially expressed in GCTB, thus building a molecular profile of this tumor. We performed quantitative real-time polymerase chain reaction (qPCR), immunohistochemistry and analyses of methylation to identify genes that are putatively associated with GCTB. The expression of the ADAM23 and CDKN2A genes was decreased in GCTB samples compared to normal bone tissue, measured by qPCR. Additionally, a high hypermethylation frequency of the promoter regions of ADAM23 and CDKN2A in GCTB was observed. The expression of the MAP2K3, MMP14, TIMP2 and VIM genes was significantly higher in GCTB than in normal bone tissue, a fact that was confirmed by qPCR and immunohistochemistry. The set of genes identified here furthers our understanding of the molecular basis of GCTB.

Giant Cardiac Fibroma: An Unusual Cause of Failure to Thrive

Cardiac fibromas are extremely rare in the general pediatric population and may present with a wide spectrum of clinical signs, including life-threatening arrhythmias and sudden death. We report a 14-month-old boy who presented with failure to thrive as the only symptom. Echocardiography showed a large cardiac fibroma in the right ventricle. Cardiac magnetic resonance imaging confirmed the diagnosis. After complete surgical tumor resection, the boy showed normal catch-up growth. This case underlines the diversity of clinical features of cardiac tumors, which implies that they should be considered early in the differential diagnosis of infants with failure to thrive.

Lethal giant discs, a novel C2 domain protein, restricts Notch activation during endocytosis

The Notch signaling pathway plays a central role in metazoan growth and patterning, and its deregulation leads to many human diseases, including cancer. It is therefore important to understand the modes of Notch signaling regulation. Recent discoveries have demonstrated that mutations in conserved endosomal pathway components such as Erupted and Vps25 can ectopically activate Notch signaling in Drosophila. Mutations in the tumor suppressor lethal giant discs (lgd) display similar but even stronger and more specific Notch activation than in the erupted and vps25 mutant animals. This Notch activation in lgd mutant tissues causes hyperplastic overgrowth of the Drosophila imaginal discs, and the eventual lethality of the animal. However, the gene that encodes Lgd, and its function in the Notch pathway have not yet been identified. ^ I have found that Lgd is a novel, conserved C2 domain protein that regulates Notch trafficking. Lgd cell-autonomously restricts Notch signaling in the Drosophila wing disc to the target cells in the D/V boundary. The function of Lgd lies at or upstream of Notch S3 activation, but Lgd doesn't affect the binding affinities between Notch and Delta. Lgd is also not required for cis-inhibition of Notch signaling by ligands. Notch accumulates on the early endosome in lgd mutant cells and signals in a ligand-independent manner, a result that has previously been seen in endosomal pathway mutants. Interestingly, Notch activation in lgd mutant cells is dependent on the endosomal protein Hrs, and Lgd activity appears to be downstream of Hrs function in endocytosis. Taken together, my data identify Lgd as a novel tumor suppressor protein that regulates Notch signaling by targeting Notch for degradation or recycling. ^

Giant clams and rising CO2: light may ameliorate effects of ocean acidification on a solar-powered animal

Global climate change and ocean acidification pose a serious threat to marine life. Marine invertebrates are particularly susceptible to ocean acidification, especially highly calcareous taxa such as molluscs, echinoderms and corals. The largest of all bivalve molluscs, giant clams, are already threatened by a variety of local pressures, including overharvesting, and are in decline worldwide. Several giant clam species are listed as 'Vulnerable' on the IUCN Red List of Threatened Species and now climate change and ocean acidification pose an additional threat to their conservation. Unlike most other molluscs, giant clams are 'solar-powered' animals containing photosynthetic algal symbionts suggesting that light could influence the effects of ocean acidification on these vulnerable animals. In this study, juvenile fluted giant clams Tridacna squamosa were exposed to three levels of carbon dioxide (CO2) (control ~400, mid ~650 and high ~950 µatm) and light (photosynthetically active radiation 35, 65 and 304 µmol photons/m**2/s). Elevated CO2 projected for the end of this century (~650 and ~950 µatm) reduced giant clam survival and growth at mid-light levels. However, effects of CO2 on survival were absent at high-light, with 100% survival across all CO2 levels. Effects of CO2 on growth of surviving clams were lessened, but not removed, at high-light levels. Shell growth and total animal mass gain were still reduced at high-CO2. This study demonstrates the potential for light to alleviate effects of ocean acidification on survival and growth in a threatened calcareous marine invertebrate. Managing water quality (e.g. turbidity and sedimentation) in coastal areas to maintain water clarity may help ameliorate some negative effects of ocean acidification on giant clams and potentially other solar-powered calcifiers, such as hard corals.

Variability of Arundo donax growth in dry-farming as a function of soil properties

Arundo donax L., commonly known as giant reed or arundo, is a perennial rhizomatous grass that has been studied since the decade of 1980 for bioenergy. In the Mediterranean region -characterised by dry and hot summers- arundo is usually grown with the support of irrigation. However, there is evidence that this plant species can tolerate dry-farming conditions once the crop is fully established. In this work the variation observed in plant growth of a 5-year-old arundo crop when the management changed from irrigated to dry-farming, is assessed. The hypothesis underlying this work was that punctual variations of soil properties might be responsible for the differences observed in plant growth

Neoplastic development: paradoxical relation between impaired cell growth at low population density and excessive growth at high density.

The role of heritable, population-wide cell damage in neoplastic development was studied in the 28 L subline of NIH 3T3 cells. These cells differ from the 17(3c) subline used previously for such studies in their lower frequency of "spontaneous" transformation at high population density and their greater capacity to produce large, dense transformed foci. Three cultures of the 28 L subline of NIH 3T3 cells were held under the constraint of confluence for 5 wk (5 wk 1 degree assay) and then assayed twice in succession (2 degrees and 3 degrees assays) for transformed foci and saturation density. After the 2 degrees assay, the cells were also passaged at low density to determine their exponential growth rates and cloned to determine the size and morphological features of the colonies. Concurrent measurements were made in each case with control cells that had been kept only in frequent low-density passages and cells that had been kept at confluence for only 2 wk (2 wk 1 degree). Two of the three cultures transferred from the 2 degrees assay of the 5 wk 1 degree cultures produced light transformed foci, and the third produced dense foci. The light focus-forming cultures grew to twice the control saturation density in their 2 degrees assay and 6-8 times the control density in the 3 degrees assay; saturation densities for the dense focus formers were about 10 times the control values in both assays. All three of the cultures transferred from the 2 degrees assay of the 5 wk 1 degree cultures multiplied at lower rates than controls at low densities, but the dense focus formers multiplied faster than the light focus formers. The reduced rates of multiplication of the light focus formers persisted for > 50 generations of exponential multiplication at low densities. Isolated colonies formed from single cells of the light focus formers were of a lower population density than controls; colonies formed by the dense focus formers were slightly denser than the controls but occupied only half the area. A much higher proportion of the colonies from the 5 wk 1 degree cultures than the controls consisted of giant cells or mixtures of giant and normal-appearing cells. The results reinforce the previous conclusion that the early increases in saturation density and light focus formation are associated with, and perhaps caused by, heritable, population-wide damage to cells that is essentially epigenetic in nature. The more advanced transformation characterized by large increases in saturation density and dense focus formation could have originated from rare genetic changes, such as chromosome rearrangements, known to occur at an elevated frequency in cells destabilized by antecedent cellular damage.

Mouse cellular cementum is highly dependent on growth hormone status

Cementum is known to be growth-hormone (GH)-responsive, but to what extent is unclear. This study examines the effects of extremes of GH status on cementogenesis in three lines of genetically modified mice; GH excess (giant), GH antagonist excess (dwarf), and GH receptor-deleted (GHR-KO) (dwarf). Age-matched mandibular molar tissues were processed for light microscope histology. Digital images of sections of first molar teeth were captured for morphometric analysis of lingual root cementum. Cross-sectional area of the cellular cementum was a sensitive guide to GH status, being reduced nearly 10-fold in GHR-KO mice, three-fold in GH antagonist mice, and increased almost two-fold in giant mice (p

Phylogenetic position and ultrastructure of two Dermocystidium species (Ichthyosporea) from the common perch (Perca fluviatilis)

Sequences of small-subunit rRNA genes were determined for Dermocystidium percae and a new Dermocystidium species established as D. fennicum sp. n. from perch in Finland. On the basis of alignment and phylogenetic analysis both species were placed in the Dermocystidium-Rhinosporidium clade within Ichthyosporea, D. fennicum as a specific sister taxon to D. salmonis, and D. percae in a clade different from D. fennicum. The ultrastructures of both species well agree with the characteristics approved within Ichthyosporea: walled spores produce uniflagellate zoospores lacking a collar or cortical alveoli. The two Dermocystidium species resemble Rhinosporidium seeberi (as described by light microscope), a member of the nearest relative genus, but differ in that in R. seeberi plasmodia have thousands of nuclei discernible, endospores are discharged through a pore in the wall of the sporangium, and zoospores have not been revealed. The plasmodial stages of both Dermocystidium species have a most unusual behaviour of nuclei, although we do not actually know how the nuclei transform during the development. Early stages have an ordinary nucleus with double, fenestrated envelope. In middle-aged plasmodia ordinary nuclei seem to be totally absent or are only seldom discernible until prior to sporogony, when rather numerous nuclei again reappear. Meanwhile single-membrane vacuoles with coarsely granular content, or complicated membranous systems were discernible. Ordinary nuclei may be re-formed within these vacuoles or systems. In D. percae small canaliculi and in D. fennicum minute vesicles may aid the nucleus-cytoplasm interchange of matter before formation of double-membrane-enveloped nuclei. Dermocystidium represents a unique case when a stage of the life cycle of an eukaryote lacks a typical nucleus.

Influence of growth hormone on the craniofacial complex of transgenic mice

Growth hormone (GH) secretion affects bone and cartilage physiology. This study investigated the effect of GH on the size of the craniofacial structures and their angular relationship. Three different models of mice with a genetically altered GH axis were used: GH excess (giant), dwarf GH antagonist (dwarf-Ant), and dwarf GH receptor knockout (dwarf-KO) mice. Each model was compared with the corresponding wild type (Wt). Five craniofacial distances were analysed: craniofacial length, upper face height, mandibular anterior height, mandibular ramus length, and mandibular corpus length. In addition, upper and lower incisor lengths and four angular relationships, nasal bone with cranial base, maxillary plane with cranial base, mandibular plane with cranial base, and the angle of the mandible, were determined. Data were analysed by one-way ANOVA. Craniofacial length, upper face height and mandibular corpus length were significantly increased in the giant mice and significantly reduced in the dwarf mice. Mandibular anterior height and mandibular ramus length were significantly affected in the dwarf-KO mice but not in the giant mice. The length of both the upper and lower incisors was significantly increased and reduced in the giant and dwarf-KO mice, respectively. In addition, the angle of the mandible was significantly increased in the giant mice and significantly reduced in the dwarf mice. It is concluded that GH plays a major role in the growth and development of the craniofacial complex by directly and indirectly modulating the size and the angular relationships of the craniofacial structures, including the incisor teeth.

Dysregulation of placental cystathionine-β-synthase promotes fetal growth restriction

Fetal growth restriction (FGR) is characterized by the birth weight and body mass below the tenth percentile for gestational age. FGR is a major cause of perinatal morbidity and mortality and babies born with FGR are prone to develop cardiovascular diseases later in life. The underlying pathology of FGR is inadequate placental transfer of nutrients from mother to fetus, which can be caused by placental insufficiency. Hydrogen sulfide (H2S), a gaseous messenger is produced endogenously by cystathionine-lyase (Cth), cystathionine-β-synthase (CBS) and 3-mercaptopyruvate sulfurtransferase (3-MST), which are present in human placenta. Recently, we demonstrated that the dysregulation of H2S/Cth pathway is associated with preeclampsia and blockade of CSE activity induces preeclampsia-like condition in pregnant mice. We hypothesized that defect in H2S pathways promote FGR and H2S donor restores fetal growth in mice where CBS or CSE activity has been compromised. Western blotting and qPCR revealed that placental CBS expressions were significantly reduced in women with FGR. ELISA analysis showed reduced placental growth factor production (PlGF) from first trimester (8–12 weeks gestation) human placental explants following inhibition of CBS activity by aminooxyacetic acid (AOA). Administration of AOA to pregnant mice had no effects on blood pressure, but caused fetal growth restriction. This was associated with reduced PlGF production. Histological analysis revealed a reduction in the placental junction zone, within which trophoblast giant cells and glycogen cells were less prominent in CBS inhibitor treated mice. These results imply that placental CBS is required for placental development and that dysregulation of CBS activity may contribute to the pathogenesis of FGR but not preeclampsia.