bluuebunny/crossref_metadata_2025 huggingface dataset:
The proteasome: molecular machinery and pathophysiological roles
Authors: Tanaka Keiji , Mizushima Tsunehiro , Saeki Yasushi
Published: March 2012

The 26S proteasome, in collaboration with ubiquitin, operates the energy-dependent regulated proteolysis process in eukaryotic cells. Over the past 30 years, several studies have comprehensively characterized the structure and molecular/physiological functions of the 26S proteasome. It is a sophisticated 2.5-MDa protein degradation machine comprising a proteolytic core particle (CP) and one or two terminal regulatory particle(s) (RP). The CP consists of two outer α rings and two inner β rings, which are made up of seven structurally similar α and β subunits, respectively. The CP contains catalytic threonine residues (β1, β2, and β5; caspase-like, trypsin-like, and chymotrypsin-like activities, respectively) on the inner surface of the chamber formed by two abutting β rings. Intriguingly, the immunotype proteasomes, named ‘immunoproteasome’ and ‘thymoproteasome’, whose catalytic subunits are replaced by the related counterparts, were discovered lately. Both unique isoenzymes essentially contribute to the acquisition of adaptive immunity in vertebrates. The RP, which serves to recognize polyubiquitylated substrate proteins and plays a role in their deubiquitylating, unfolding, and translocation into the interior of the CP for destruction, forms two subcomplexes: the base and the lid. On another front, the PA28 and PA200, alternative CP activator proteins discovered biochemically, both play independent roles in proteolysis of the 26S proteasome. Several studies have highlighted the importance of the proteasome in various intractable diseases that have been increasing in the aged society of the 21st century.
ELF and the inconvenience of established concepts
Authors: Widdowson, H. G.
Published: March 2012

The purpose of this article is to put ELF in broader perspective and to speculate on how it raises general epistemological and practical issues in (socio)linguistics and language pedagogy. Such issues have not escaped the notice of ELF researchers, of course, and so this paper will have nothing to offer in the way of revelation. My intention is not to argue for the legitimacy of ELF study as such but to consider its effect as a catalyst for change in established ways of thinking. We can only make sense of the world by imposing our own order on it by devising abstract constructs so as to bring it under conceptual control. This is as true of linguistics and language pedagogy as of everything else: both of them necessarily disconnect the continuum of actual experience to make simplifying distinctions so as to come to terms with reality – distinctions between languages and varieties, for example, between competence and performance, between language learners and users. Making abstract distinctions of one kind or another is a necessary convenience and cannot be avoided, but having made them, we need also to consider how they are related and how far they remain convenient. What ELF research reveals so clearly is the need to review the distinctions that have become conventionally established in the description and the teaching of English.
Towards a post-normative approach: learning the pedagogy of ELF
Authors: Dewey, Martin
Published: March 2012

This paper considers the impact on pedagogy of ELF research and theory in relation to language teacher education and development. As has been much remarked, research in ELF has reached the point where established principles and sanctioned good practice in ELT (English Language Teaching) require substantial reassessment. Empirical work and theoretical discussions pose profound questions to the ELT profession, with major implications for common beliefs and assumptions about all manner of concerns, especially the language syllabus, teaching materials, and language assessment. Yet, as we have also seen, any discussion of major change in pedagogy tends to provoke controversy and unease among practitioners. There has thus far been relatively little in-depth exploration of what teachers might do to incorporate an ELF perspective in practice. Modifying the curriculum or materials in response to ELF requires fundamental rethinking and (re)training in approaches to teaching. This paper reports ongoing attempts to engage and work collaboratively with ELF-aware teachers to re-examine current methodology and practice in context- relevant ways. Only by working with teachers can we properly explore the feasibility of incorporating an ELF perspective in order to move beyond a norm-driven approach.
Influence of the specimen thickness on low velocity impact behavior of composites
Authors: Amaro Ana M. , Reis Paulo Nobre Balbis , de Moura Marcelo , Santos Jaime B.
Published: March 2012

In this work, the influence of specimen thickness on low velocity impact behavior of carbon-epoxy composite laminates is studied. Plates with different thicknesses were tested under low velocity impact using a hemispherical impactor. The internal damage was mainly constituted by delaminations which were evaluated through the inspection of the impacted plates by the ultrasonic C-scan technique. It was observed that delaminations increase with plate thickness. In order to better understand the physical phenomenon explaining this result, a progressive damage model was used to simulate composites behavior under low velocity impact. In this context, a three-dimensional numerical analysis considering interface finite elements, including a cohesive mixed-mode damage model, which allows simulating delaminations onset and growth between layers, was performed. Good agreement was obtained between experimental and numerical analysis, which validated the proposed procedure. In addition, the proposed numerical methodology allowed identification of physical phenomena related to the influence of plate thickness on delamination size.
A quantitative approach to assess the mixing ability of single-screw extruders for polymer extrusion
Authors: Domingues Natália , Gaspar-Cunha António , Covas José António
Published: March 2012

Models to predict the evolution of the morphology of immiscible liquid-liquid systems and of solid agglomerates dispersion in single-screw extruders were adapted to compute global distributive and dispersive mixing indices. Using these indices, the direct assessment of the mixing ability of a given screw or a comparison of distinct screws becomes readily available. In the case of liquid-liquid systems, the degree of distributive mixing is computed from the extent of deformation of the individual drops, whereas the degree of dispersive mixing is determined by the reduction in drop size. For solid-liquid systems, distributive mixing is quantified by a normalized Shannon entropy, whereas dispersive mixing is defined from the extent of size reduction. The effect of material properties, operating conditions, and geometry of the screw and die is investigated. Finally, the indices are used to determine (via optimization) the operating conditions and the screw geometry that maximize the mixing efficiency.
Activation of Cannabinoid Receptor 2 Attenuates Leukocyte–Endothelial Cell Interactions and Blood–Brain Barrier Dysfunction under Inflammatory Conditions
Authors: Ramirez Servio H. , Haskó János , Skuba Andrew , Fan Shongshan , Dykstra Holly , McCormick Ryan , Reichenbach Nancy , Krizbai Istvan , Mahadevan Anu , Zhang Ming , Tuma Ronald , Son Young-Jin , Persidsky Yuri
Published: March 2012

Previous studies have shown that modulation of the receptor-mediated cannabinoid system during neuroinflammation can produce potent neuroprotective and anti-inflammatory effects. However, in this context, little is known about how selective activation of the cannabinoid type-2 receptor (CB2R) affects the activated state of the brain endothelium and blood–brain barrier (BBB) function. Using human brain tissues and primary human brain microvascular endothelial cells (BMVECs), we demonstrate that the CB2R is highly upregulated during inflammatory insult. We then examined whether the CB2R agonists could attenuate inflammatory responses at the BBB using a mouse model of LPS-induced encephalitis and highly selective CB2R agonists. Visualization by intravital microscopy revealed that administration of JWH133 [(6aR,10aR)-3-(1,1-dimethylbutyl)-6a,7,10,10a-tetrahydro-6,6,9-trimethyl-6H-dibenzo[b,d]pyran] or a novel resorcinol-based compound, O-1966 (1-[4-(1,1-dimethyl-heptyl)-2,6-dimethoxy-phenyl]-3-methyl-cyclohexanol), greatly attenuated leukocyte adhesion in surface pial vessels and in deep ascending cortical postcapillary venules. BBB permeability assessments with small and large fluorescent tracers showed that CB2R agonists were effective at preventing barrier leakiness after LPS administration. To determine whether the effects by CB2R agonists on barrier protection are not only due to the CB2R modulation of immune cell function, we tested the agonistsin vitrowith barrier-forming primary BMVECs. Remarkably, the addition of CB2R agonist increased transendothelial electrical resistance and increased the amount of tight junction protein present in membrane fractions. Furthermore, CB2R agonists decreased the induction of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 surface expression in BMVECs exposed to various proinflammatory mediators. Together, these results suggest that pharmacological CB2R ligands offer a new strategy for BBB protection during neuroinflammation.
Traumatic Alterations in GABA Signaling Disrupt Hippocampal Network Activity in the Developing Brain
Authors: Dzhala Volodymyr , Valeeva Guzel , Glykys Joseph , Khazipov Rustem , Staley Kevin
Published: March 2012

Severe head trauma causes widespread neuronal shear injuries and acute seizures. Shearing of neural processes might contribute to seizures by disrupting the transmembrane ion gradients that subserve normal synaptic signaling. To test this possibility, we investigated changes in intracellular chloride concentration ([Cl−]i) associated with the widespread neural shear injury induced during preparation of acute brain slices. In hippocampal slices and intact hippocampal preparations from immature CLM-1 mice, increases in [Cl−]icorrelated with disruption of neural processes and biomarkers of cell injury. Traumatized neurons with higher [Cl−]idemonstrated excitatory GABA signaling, remained synaptically active, and facilitated network activity as assayed by the frequency of extracellular action potentials and spontaneous network-driven oscillations. These data support a more inhibitory role for GABA in the unperturbed immature brain, demonstrate the utility of the acute brain slice preparation for the study of the consequences of trauma, and provide potential mechanisms for both GABA-mediated excitatory network events in the slice preparation and early post-traumatic seizures.
Binaural Interactions Develop in the Auditory Brainstem of Children Who Are Deaf: Effects of Place and Level of Bilateral Electrical Stimulation
Authors: Gordon Karen A. , Salloum Claire , Toor Gurvinder S. , van Hoesel Richard , Papsin Blake C.
Published: March 2012

Bilateral cochlear implants (CIs) might promote development of binaural hearing required to localize sound sources and hear speech in noise for children who are deaf. These hearing skills improve in children implanted bilaterally but remain poorer than normal. We thus questioned whether the deaf and immature human auditory system is able to integrate input delivered from bilateral CIs. Using electrophysiological measures of brainstem activity that include the Binaural Difference (BD), a measure of binaural processing, we showed that a period of unilateral deprivation before bilateral CI use prolonged response latencies but that amplitudes were not significantly affected. Tonotopic organization was retained to some extent as evidenced by an elimination of the BD with large mismatches in place of stimulation between the two CIs. Smaller place mismatches did not affect BD latency or amplitude, indicating that the tonotopic organization of the auditory brainstem is underdeveloped and/or not well used by CI stimulation. Finally, BD amplitudes decreased when the intensity of bilateral stimulation became weighted to one side and this corresponded to a perceptual shift of sound away from midline toward the side of increased intensity. In summary, bilateral CI stimulation is processed by the developing human auditory brainstem leading to perceptual changes in sound location and potentially improving hearing for children who are deaf.
LIM Domain Only 4 (LMO4) Regulates Calcium-Induced Calcium Release and Synaptic Plasticity in the Hippocampus
Authors: Qin Zhaohong , Zhou Xun , Gomez-Smith Mariana , Pandey Nihar R. , Lee Kevin F. H. , Lagace Diane C. , Béïque Jean-Claude , Chen Hsiao-Huei
Published: March 2012

The LIM domain only 4 (LMO4) transcription cofactor activates gene expression in neurons and regulates key aspects of network formation, but the mechanisms are poorly understood. Here, we show that LMO4 positively regulates ryanodine receptor type 2 (RyR2) expression, thereby suggesting that LMO4 regulates calcium-induced calcium release (CICR) in central neurons. We found that CICR modulation of the afterhyperpolarization in CA3 neurons from mice carrying a forebrain-specific deletion of LMO4 (LMO4 KO) was severely compromised but could be restored by single-cell overexpression of LMO4. In line with these findings, two-photon calcium imaging experiments showed that the potentiation of RyR-mediated calcium release from internal stores by caffeine was absent in LMO4 KO neurons. The overall facilitatory effect of CICR on glutamate release induced during trains of action potentials was likewise defective in LMO4 KO, confirming that CICR machinery is severely compromised in these neurons. Moreover, the magnitude of CA3-CA1 long-term potentiation was reduced in LMO4 KO mice, a defect that appears to be secondary to an overall reduced glutamate release probability. These cellular phenotypes in LMO4 KO mice were accompanied with deficits in hippocampus-dependent spatial learning as determined by the Morris water maze test. Thus, our results establish LMO4 as a key regulator of CICR in central neurons, providing a mechanism for LMO4 to modulate a wide range of neuronal functions and behavior.
TrkAGene Ablation in Basal Forebrain Results in Dysfunction of the Cholinergic Circuitry
Authors: Sanchez-Ortiz Efrain , Yui Daishi , Song Dongli , Li Yun , Rubenstein John L. , Reichardt Louis F. , Parada Luis F.
Published: March 2012

Dysfunction of basal forebrain cholinergic neurons (BFCNs) is an early pathological hallmark of Alzheimer's disease (AD). Numerous studies have indicated that nerve growth factor (NGF) supports survival and phenotypic differentiation of BFCNs. Consistent with a potential link to AD pathogenesis, TrkA, a NGF receptor, is expressed in cholinergic forebrain neuronal populations including those in BF and striatum, and is markedly reduced in individuals with mild cognitive impairment (MCI) without dementia and early-stage AD. To investigate the role of TrkA in the development, connectivity, and function of the BF cholinergic system and its contribution to AD pathology, we have generated a forebrain-specific conditionalTrkAknock-out mouse line. Our findings show a key role for TrkA signaling in establishing the BF cholinergic circuitry through the ERK pathway, and demonstrate that the normal developmental increase of choline acetyltransferase expression becomes critically dependent on TrkA signaling before neuronal connections are established. Moreover, the anatomical and physiological deficits caused by lack of TrkA signaling in BFCNs have selective impact on cognitive activity. These data demonstrate that TrkA loss results in cholinergic BF dysfunction and cognitive decline that is reminiscent of MCI and early AD.
Soft Microorigami: Stimuli-Responsive Self-Folding Polymer Films
Authors: Ionov Leonid , Zakharchenko Svetlana , Stoychev Georgi , Sperling Evgeni
Published: March 2012

Asymmetry is intrinsic to natural systems and is widely used by living organisms for efficient adaptation, mimicry and movement. Polymer bilayers are the example of synthetic asymmetric systems, which are able to generate macroscopic motion and fold by forming different 3D objects such as tubes and capsules. Similar to bimetal films, the polymer bilayer consist of two substances with different swelling properties. One polymer is non-swellable and hydrophobic. Another polymer is water-swellable hydrogel. The folding, which might occur in response to temperature or pH, is caused by swelling of the hydrogel layer. The formed tubes and capsules can be manipulated using magnetic field. Reversible folding and unfolding of the polymer films is applied for reversible capture and release of cells in response to change of temperature and other signals. This novel biomimetic approach can be used for controlled encapsulation and release of microparticles, cells and drugs as well as fabrication of 3D scaffolds for tissue engineering.
Gone but Not Forgotten? Invasive Plants' Legacies on Community and Ecosystem Properties
Authors: Corbin Jeffrey D. , D'Antonio Carla M.
Published: March 2012

The widespread recognition that nonnative plants can have significant biological and economic effects on the habitats they invade has led to a variety of strategies to remove them. Removal alone, however, is often not sufficient to allow the restoration of altered communities or ecosystems. The invasive plant's effects may persist after its removal thus exerting a “legacy” that influences community composition or the ecosystem properties or both over some ensuing period. Here, we review evidence of such legacy effects on plant and soil communities, soil chemistry, and soil physical structure. We discuss this evidence in the context of efforts to restore community composition and ecosystem function in invaded habitats. Legacies are especially likely to develop in cases where invasive species cause local extirpations of resident species, alter resource pools, and interact with other aspects of global change including land-use changes, atmospheric N deposition, acid rain, and climate change. In cases where legacies of invasive plants develop, the removal of the nonnative species must also be accompanied by strategies to overcome the legacies if restoration goals are to be achieved.
Water resistance of composite binders containing phosphogpysum with different pretreatment processes
Authors: Ren Tingyan , Zhu Jing , Liu Wanchao , Zhu Xinfeng , Yang Jiakuan
Published: March 2012

The influence of pretreated phosphogypsum on water resistance of composite binders containing phosphogypsum (CBPG) was investigated. Six pretreatment processes in total were conducted on phosphogypsum using autoclaving and calcination. Three parameters of the CBPG mortars were comparatively studied to evaluate their water resistance: the ratio of the compressive strength in the wet-saturated state to that in the dry state (W/D); weight loss after static water attack (WLSW); and weight loss after flowing water attack (WLFW). The crystalline phases could be transformed and the impurities could be effectively purified for original phosphogypsum by the pretreatment process. Therefore, water resistance of the CBPG mortars from pretreated phosphogypsum was improved significantly when compared to that of the mortars from original phosphogypsum. Regarding the weight loss and strength after static or flowing water attacks, WLSW and WLFW could effectively evaluate the water resistance of CBPG mortars, when compared with traditional evaluation by W/D.
Modified Bolomey equation for strengths of lightweight concretes containing fly ash aggregates
Authors: Rajamane N. P. , Ambily P. S.
Published: March 2012

The Bolomey equation has been used for relating the cement–water ratio to compressive strengths of concrete containing normal weight aggregate. This is basically a linear equation, not considering explicitly the parameters relating to coarse aggregates. Strengths of lightweight concretes containing fly ash aggregates (FAAs) are influenced both by cement–water ratio and the properties of the aggregates. It is generally very difficult explicitly to determine the properties of lightweight aggregates (such as FAAs). In view of this, a modified Bolomey equation, considering indirectly the presence of FAAs, is suggested in this paper, using the experimental data generated at the Structural Engineering Research Centre, Chennai. Applicability of this formula is checked with reference to the published data.
Ultrastructural Features of Cyclosporine A‐Induced Gingival Hyperplasia
Authors: Mariani Giustiniano , Calastrini Carla , Carinci Francesco , Marzola Riccardo , Calura Giorgio
Published: March 2012

The present work collected data on the ultrastructural features of the attached gingiva in kidney transplant patients who showed gingival hyperplasia following cyclosporin A (Cy A) treatment. Ultrastructural examination was carried out on biopsies of attached gingiva obtained from 8 male patients (30 to 60 years old) undergoing treatment at the Dental Clinic of the University of Ferrara. The data showed that, although many fibroblasts are present in Cy A‐induced hyperplasia, there is a particular abundance of amorphous substance compared to fibrous, as well as marked plasma cell infiltration. On the basis of the data collected, we hypothesize that the morphological features of the dimensional increase in gingival tissue associated with Cy A treatment in kidney transplant patients may be considered local manifestations of a systemic phenomenon. J Periodontol 1993; 64:1092–1097.
Osteopromotion: A Soft‐Tissue Exclusion Principle Using a Membrane for Bone Healing and Bone Neogenesis
Authors: Linde Anders , Alberius Per , Dahlin Christer , Bjurstam Kerstin , Sundin Yvonne
Published: March 2012

The research reviewed in this paper constitutes a series of investigations intended to develop and evaluate a new membrane technique, which provides improved conditions for osteogenesis during healing of bone defects and restitution of earlier existing bone. The technique has also been shown to aid in bone grafting as well as having the capacity to create new bone for reconstructive purposes. According to this methodology, membranes are utilized to create a space in the tissue in which osteogenesis can occur relatively unimpeded. The paper provides a review of our initial animal experimental work as well as some clinical studies with special emphasis on membrane use in conjunction with dental implants. Possible mechanisms behind the efficacy of the membrane technique are reviewed, and future perspectives of development are also discussed. The osteopromotive membrane technique represents a principally new and major advance in bone biology and reconstructive skeletal surgery. Based on the results obtained by us and by others, the technique is presently utilized clinically in some routine applications. J Periodontol 1993; 64:1116–1128.
Treatment of Mandibular 3‐Wall Intrabony Defects by Flap Debridement and Expanded Polytetrafluoroethylene Barrier Membranes. Long‐Term Evaluation of 32 Treated Patients
Authors: Becker William , Becker Burton E.
Published: March 2012

The purpose of this study was to evaluate the healing potential of deep, primarily 3wall intrabony defects which were treated by flap debridement and expanded polytetrafluoroethylene (ePTFE) membranes and followed for extended time periods. All of the treated defects were in the mandibular arch. Thirty‐two patients were treated and reexamined at an average of 3 years 5 months. Twenty‐four of these patients had re‐entry procedures at the second examination. Sixteen of these patients were examined a third time at an average of 4 years 3 months. The patients were evaluated for changes in probing depth (PD), clinical attachment level (CAL), recession, changes in crestal resorption, and defect bone fill. The paired t‐test for related samples was used to test for differences between examinations. Between Exams 1 and 2 there was a statistically significant reduction of pocket depth (3.8 mm), gain in clinical attachment level (4.2 mm), and an increase in recession (−1.2 mm). For the 24 patients who had re‐entry procedures there was an average defect fill of 4.3 mm (P < 0.0001) and 0.33 mm of crestal resorption (P < 0.0001). The 16 patients who were examined 3 times sustained decreases in PD, gains in CAL, and recession recorded at the second examination. These changes were statistically significant at Exam 3. The results of this study demonstrate that deep, 3‐wall intrabony defects treated by debridement and ePTFE barrier membranes will have significant decreases in PD, gains in CAL, recession, decreases in crestal resorption, and gains in bone fill. These gains can be maintained over extended time intervals and are considered to be predictable. J Periodontol 1993; 64:1138–1144.
Guided Tissue Regeneration in Mucogingival Surgery
Authors: Tinti Carlo , Vincenzi Giampaolo , Cocchetto Roberto
Published: March 2012

The use of expanded polytetrafluoroethylene (ePTFE) membranes in the treatment of mucogingival problems such as gingival recession, has been recently described. The major issues raised dealt with creating and maintaining space under the membrane and designing a flap that could be coronally positioned and at the same time capable of maintaining a good blood supply. The authors proposed the use of a trapezoidal flap and some technical space‐making solutions, such as the use of a suturing technique and different metal structures to support the membranes. J Periodontol 1993; 64:1184–1191.
In Situ Characterization of Gingival Mononuclear Cells in Rapidly Progressive Periodontitis
Authors: Çelenligil Haviye , Kansu Emin , Ruacan Şevket , Eratalay Kenan , Çaǵlayan Gürhan
Published: March 2012

Rapidly progressive Periodontitis (RPF) has been suggested as a distinct clinical entity within the spectrum of early onset Periodontitis. Immunological mechanisms have been considered in the pathogenesis of RPP. This study was designed to evaluate the distribution and phenotypic properties of the lymphocyte populations within the affected gingival tissue of patients with RPP. Biopsies were obtained from 16 patients between 22 and 33 years of age. The tissue samples were processed for both histopathological and immunohistochemical examinations. Gingival tissue T lymphocytes (CD3+), helper T cells (CD4+), suppressor‐cytotoxic T cells (CD8+), and cells positive for HLA‐DR antigen were identified using monoclonal antibodies with an immunoperoxidase technique. Intracytoplasmic immunoglobulin‐containing cells were also stained immunohistochemically with polyclonal antibodies. CD3+ cells were mainly located beneath the pocket epithelium. CD4+ and CD8+ cells were evenly distributed within this T‐cell infiltrate with a CD4+/CD8+ ratio of 1:12. Numerous HLA‐DR+ cells were also observed in the lymphocytic infiltrates. The majority of mononuclear cells located throughout the stroma were IgG+ plasma cells. Our results indicate that RPP patients present an IgGbearing plasma cell dominated lesion with equal participation of both T‐cell subpopulations. These findings suggest that activation and proliferation of B‐cells play an important role in the pathogenesis of periodontal diseases. J Periodontol 1993; 64:120– 127.
Mitogenic Effects of Growth Factors on Human Periodontal Ligament Cells In Vitro
Authors: Oates Thomas W. , Rouse Cheryl A. , Cochran David L.
Published: March 2012

Periodontal regeneration is thought to require the migration and proliferation of periodontal ligament cells. Evidence suggests that the Polypeptide growth factors PDGF, IL‐1, and TGF‐β are mediators of these cellular events in wound healing. The purpose of this study was to determine the effects of these growth factors on human periodontal ligament (PDL) cell mitogenesis, and to identify the regulatory influences of TGF‐β on the response to PDGF and IL‐1. Confluent, quiescent human PDL cells were cultured in vitro and treated with the Polypeptide growth factors PDGF‐AA and ‐BB, IL‐1β, and TGF‐• in both a dose and time‐dependent manner. Mitogenic activity, as a measure of proliferative potential, was determined by the quantitation of 3H‐thymidine incorporation during DNA synthesis. The results of this study demonstrated that both PDGF‐AA and ‐BB enhance mitogenic activity in a dose‐dependent manner over a concentration range of 1.0 to 50.0 ng/ml. IL‐1β (0.01 to 1.0 pM) resulted in no mitogenic enhancement, and at high concentrations (10.0 to 100.0 pM) demonstrated an inhibitory effect. TGFβ produced a significant increase (P <0.01) in mitogenic activity (although relatively much less than PDGF) in a delayed, bimodal, dose‐dependent manner over a concentration range of 0.01 to 20.0 ng/ml, with a maximal response at a concentration of 1.0 ng/ ml. Additionally, incubation with TGF‐β at 1.0 ng/ml prior to the addition of PDGF significantly enhanced (P <0.01) the mitogenic response to both PDGF‐AA and PDGFBB. In contrast, incubation with TGF‐β at a higher concentration (10.0 ng/ml) prior to PDGF addition resulted in a decreased (P <0.05) mitogenic response to PDGF‐AA, while enhancing (P <.01) the response to PDGF‐BB. This study demonstrates that PDGF‐AA and PDGF‐BB are major mitogens for human PDL cells in vitro, and supports a role for TGF‐β as a regulator of the mitogenic response to PDGF in these cells. J Periodontol 1993; 64:142–148.
Experimental Gingivitis During Pregnancy and Post‐Partum: Immunohistochemical Aspects
Authors: Raber‐Durlacher J.E. , Leene W. , Palmer‐Bouva C.C.R. , Raber J. , Abraham‐Inpijn L.
Published: March 2012

The histoimmunological response of 8 individuals was studied longitudinally in relation to the development of experimental gingivitis during pregnancy and post‐partum. At day 0 as well as at day 14 of experimental gingivitis the mean periodontal pocket bleeding index (PPBI) was higher during pregnancy than post‐partum, whereas the amount of plaque that accumulated was similar. The number of CD1 positive cells (mainly Langerhans) in the oral epithelium was found to be higher during pregnancy. In the sulcular epithelium, however, the number of these cells tended to decrease during pregnancy as compared to post‐partum. The number of CD4 positive cells in oral and sulcular epithelium was increased during pregnancy (P <0.05). It was speculated that this increase in the number of CD4 positive cells is confined to the Th‐1 subset, since the number of CD14 positive cells (mainly macrophages and granulocytes) together with the number of B cells was found to be decreased during pregnancy. Th‐1 cells are known to be cytotoxic against these HLA class II antigen bearing cells. Consequently, cytotoxicity directed against B cells and macrophages may result in diminished immunoresponsiveness in pregnancy gingivitis. J Periodontol 1993; 64:211–218.
Histologic Assessment of New Attachment Following the Treatment of a Human Buccal Recession by Means of a Guided Tissue Regeneration Procedure
Authors: Cortellini P. , Clauser C. , Prato G.P. Pini
Published: March 2012

A deep, long‐standing recession on a mandibular incisor was treated in a 56‐yearold female patient. The tooth was tilted buccally and was scheduled for extraction. The recession was 8 mm deep, with a pocket depth of 1 mm and no keratinized tissue. The recession was treated by guided tissue regeneration; the membrane was left in place for 4 weeks. The tooth was extracted along with marginal tissues 5 months after the removal of the membrane. At the time of extraction, 4 mm of root coverage had been achieved and 3 mm of keratinized tissue were measured buccally. Histologic measurements showed that 3.66 mm of new connective tissue attachment had been obtained associated with newly formed cementum (2.48 mm) and bone growth (1.84 mm). The crestal bone level after treatment was located coronal to the preoperative location of the gingival margin. J Periodontol 1993;64:387–391.
A 2‐Year Study of Adjunctive Minocycline‐HCl in Actinobacillus actinomycetemcomitans‐Associated Periodontitis
Authors: Müller Hans‐Peter , Lange Dieter E. , Mïller Rüiger F.
Published: March 2012

To study the effects of a step‐wise treatment regimen on Actinobacillus actinomycetemcomitans‐(Aa) associated periodontitis, 4 clusters among 33 patients harboring the organism were followed during successive periods of systemic minocycline plus mechanical debridement and minocycline plus modified Widman flap treatment. Localized Periodontitis was found in 2 clusters, one with 7 localized juvenile periodontitis patients and a 24‐year old male with localized destruction and extremely low plaque levels (UP), and the other consisting of 10 patients with plaque and gingivitis and a wider age range (16 to 54 years, LP). Generalized severe and moderate periodontitis was found in 2 clusters which were further discriminated by severe gingivitis and high levels of supragingival plaque (9 patients, GSP), and mild inflammation and low plaque levels (6 patients, GMP). Mean percentages of Aa, as determined by selective cultivation of microbiota from at least 2 periodontal pockets of 6 mm or more were 63, 16, 33, and 7.8% in the clusters (P <0.01). Six months after active treatment, Aa was present in 6/9 patients and 50% of sites in GSP, and 3/6 patients and 46% of sites in GMP patients. In contrast, the organism was virtually eliminated by scaling and flap procedures in the localized periodontitis clusters, and did not reappear after 6 months (P <0.05). Combined antibiotic, mechanical, and surgical therapy resulted in a persistence of 20% of sites with residual probing depth of ≥ 4 mm in GMP patients after active therapy. At this point, 3 of the GMP patients and 1 GSP patient left the study. Multiple regression analysis showed a significant influence of log‐transformed numbers in Aa in cheek and saliva samples at the end of the study, and cluster on the percent residual number of sites with periodontal probing depth of ≥ 7 mm (P <0.001). The present results suggest that the applied therapy would be appropriate in localized forms of Aa Periodontitis, but inappropriate in more severe and generalized forms to predictably eliminate Aa. Controlled long‐term studies with larger groups of patients will be needed to establish the difference in treatment response suggested by these studies. J Periodontol 1993; 64:509–519.
Effects of Nd:YAG Laser Radiation on Removal of a Root Surface Smear Layer after Root Planing: A Scanning Electron Microscopic Study
Authors: Ito Koichi , Nishikata Jun‐ichi , Murai Seidai
Published: March 2012

A scanning electron microscopy (SEM) study was conducted to evaluate the effects of Nd:YAG laser radiation on removal of a root surface smear layer after root planing in comparison with citric acid treatment. The experimental materials were 15 human teeth affected by severe periodontal disease, which were extracted because of a hopeless prognosis. The teeth had at least 5 mm of attachment loss on the proximal surface tested. After removing all visible calculus using an ultrasonic sealer, each proximal surface was vigorously scaled and root planed with a Gracey curet. Thirty specimens were cut from the root‐planed proximal surfaces and assigned randomly to one of two groups: Group A (25 specimens) was divided into 5 subgroups and irradiated with a Nd:YAG laser, using non‐contact delivery (3 mm beam diameter, distance from the tip to the specimen 5 cm), at a measured power of 20 W for 0.3, 0.5, 1.0, 2.0, or 3.0 seconds corresponding to energy densities of 84.93, 141.54, 283.09, 566.17, or 849.26 J/cm2; Group B (5 specimens) was not irradiated, but treated for 3 minutes with saturated citric acid (pH 1). The center of each specimen in Group A was used as the experimental area (Exp A) treated by laser irradiation and the peripheral area of the specimen served as a control (Cont A). In Group B, one half of the specimen was used as the experimental area (Exp B) treated by citric acid and the other half served as a control (Cont B). The specimens were then fixed and examined by SEM. The surface of the root‐planed specimens (Cont A and B) was irregular, corresponding to the presence of a smear layer, and had an amorphous appearance. Both root surfaces of Exp A and B exhibited clear orifices of dentinal tubules and intertubular dentin without a smear layer. Although the root surface of Exp A showed clear orifices of dentinal tubules with a flat morphology, the root surface of Exp B showed widened funnel‐shaped dentinal tubule orifices with a fibrillar, mat‐like morphology. The present results indicate that Nd:YAG radiation effectively removes the smear layer, uncovers dentinal tubules, and exposes collagen fibers on the root surface without widening the orifices of dentinal tubules after root planing. J Periodontol 1993; 64:547–552.
Incisive Canal Cysts Related to Periodontal Osseous Defects: Case Reports
Authors: Mealey Brian L. , Rasch Mark S. , Braun James C. , Fowler Craig B.
Published: March 2012

The incisive canal cyst is the most common non‐odontogenic cyst of the oral cavity. While the cyst has frequently been described, the relationship between the lesion and adjacent periodontal osseous defects has rarely been reported. This paper describes the occurrence and treatment of incisive canal cysts in two patients with severe adult Periodontitis on maxillary incisor teeth. J Priodontol 1993;64:571–574.
Serum and Gingival Crevicular Fluid Anti‐Desmosomal Antibodies in Periodontitis
Authors: Govze Y. , Herzberg M. C.
Published: March 2012

SDS polyacrylamide gel electrophoresis separates desmosomal proteins and glycoproteins of bovine tongue epithelium by their relative molecular mass. The Western immunoblot technique was used to reveal the reactions of desmosomal proteins and glycoproteins with naturally occurring antibodies in serum and gingival crevicular fluid (GCF). Naturally‐occurring serum and GCF antibodies (IgG and IgM) from periodontitis patients and healthy, unaffected controls reacted with desmosomal proteins (desmoplakins) and glycoproteins (desmogleins). Sera from 90% of subjects with periodontitis showed increased reactions of IgG with desmoplakins (240 and 210 kDa) and 80% with desmogleins (165, 130, and 115 kDa), when compared with unaffected controls. Patients' IgG reacted with desmosomal components more strongly than IgM. IgG antibodies against desmosomal antigens in GCF showed similar specificities from patients and healthy subjects and to their serums. When GCF within individuals with periodontitis was compared, anti‐desmosomal IgG from diseased sites showed greater reactivity than healthy controls. These data suggest that anti‐desmosomal antibodies are a normal part of the immune repertoire. The presence of elevated titers of anti‐desmosomal antibodies appear to distinguish periodontitis from unaffected sites. When detected, elevated titers of antidesmosomal antibodies may contribute to the pathogenesis and indicate increased risk of periodontitis. J Periodontol 1993;64:603–608.
Defective Chemotaxis and Calcium Response in Localized Juvenile Periodontitis Neutrophils
Authors: Daniel Michael A. , McDonald Georgia , Offenbacher Steven , Van Dyke Thomas E.
Published: March 2012

Localized juvenile periodontitis (ljp) is an early onset form of periodontal disease characterized by unique localization to first molars and incisors and a high prevalence of neutrophil abnormalities, particularly chemotaxis. The intracellular transduction mechanisms that follow receptor‐ligand coupling on the neutrophil surface and lead to chemotaxis are not clearly established. Chemotaxis and phagocytosis are modulated by a variety of receptors and involve several activation pathways; the role of intracellular calcium as a presumptive second messenger and mediator of these events is well established. The putative effector mechanisms for the chemotactic receptor of neutrophils also include the possible activation of a phospholipase, protein kinase C, methyltransferase, or adenylate cyclase. In normal neutrophils, a phosphoinositide pathway initiated by phospholipase C, which results in the activation of protein kinase C via diacylglycerol and the generation of IP3, has been implicated. In order to better understand the stages of neutrophil transduction, fluorescent probes were used to monitor neutrophil calcium changes. Chlorotetracycline (CTC) was used as an indirect probe of intracellular membrane‐bound pool of calcium stores, and Quin‐2 was used to monitor cytosolic free calcium levels of FMLP stimulated normal and LJP neutrophils. The results indicate that the early phase of the calcium response affiliated with the release of intracellularly sequestered calcium appears intact in LIP neutrophils, as the CTC fluorescence changes were similar to control values. The second phase of the calcium response, associated with membrane channel activation and an influx of extracellular calcium, appeared compromised in the neutrophils of the LJP population. These observations suggest an abnormality of signal transduction in LJP patients resulting in a decreased influx of extracellular calcium, perhaps due to failure in plasma membrane calcium channel activation or in an associated activation pathway. J Periodontol 1993; 64:617–621.
Subgingival Minocycline Hydrochloride Ointment in Moderate to Severe Chronic Adult Periodontitis: A Randomized, Double‐Blind, Vehicle‐Controlled, Multicenter Study
Authors: van Steenberghe Daniel , Bercy Pierre , Kohl Jacques , De Boever Jan , Adriaens Patrick , Vanderfaeillie Annelou , Adriaenssen Christian , Rompen Eric , De Vree Hilde , McCarthy Eugene F. , Vandenhoven Guy
Published: March 2012

The safety and efficacy of subgingivally‐applied 2% minocycline ointment was evaluated in a randomized, double‐blind study of 103 adults with moderate to severe periodontitis. Two groups were compared; one received the test minocycline ointment and the other a vehicle control. Both groups had scaling and root planing at baseline, after which the test or control ointments were applied with an applicator into the periodontal pockets at baseline, and at 2, 4, and 6 weeks. Assessment of clinical response was made by measuring probing depth and probing attachment level and gingival bleeding. These measurements were made at baseline prior to scaling and root planing, and at weeks 4 and 12. Microbiological assessment of the subgingival flora was carried out with DNA probes at baseline, and at weeks 2, 4, 6, and 12 to identify and quantify Porphyromonas gingivalis, Prevotella intermedia, and Actinobacillus actinomycetemcomitans. Subgingival minocycline ointment resulted in statistically significantly greater reduction of P. gingivalis at weeks 2, 4, 6, and 12; P. intermedia at weeks 2, 4, 6, and 12; and A. actinomycetemcomitans at weeks 6 and 12. Probing depth reductions were seen for both groups at weeks 4 and 12; however, this reduction was statistically significantly greater in subjects treated with minocycline ointment. Reduction in gingival index and probing attachment gain were seen in both groups, however, the differences between the groups were not statistically significant. In those sites with a baseline probing depth ≥7 mm and a bleeding index >2, the minocycline treatment at 12 weeks resulted in a probing pocket depth reduction of 42% at baseline as compared to 28% at baseline in the control group (P = 0.0001). Subgingival administration of minocycline ointment was well tolerated. This study demonstrates that repeated subgingival administration of a minocycline ointment as an adjunct to scaling and root planing results in reduction of putative periodontal pathogens, and reduction in probing depth greater than that seen in the control. J Periodontal 1993; 64:637–644.
Comparative SEM Study on the Effect of Acid Etching With Tetracycline HCl or Citric Acid on Instrumented Periodontally‐Involved Human Root Surfaces
Authors: Lafferty Thomas A. , Gher Marlin E. , Gray Jonathan L.
Published: March 2012

This study compared the surface characteristics of periodontally diseased singlerooted human teeth extracted after treatment with either tetracycline HCl or citric acid solutions. The study group was comprised of 30 teeth from 22 patients with advanced periodontal disease extracted before the start of periodontal therapy. Diseased surfaces were identified, outlined, and root planed by hand curet or finishing bur. The teeth were sectioned and solutions of tetracycline HCl or citric acid (pH 1) were applied to the surfaces with cotton pellets for 5 minutes. Extracted teeth were processed and root surface samples then examined by scanning electron microscope. The surfaces of both acidtreated sets of specimens differed considerably from specimens treated with root planing alone, regardless of root planing method. Acid‐treated specimens exhibited dentinal tubules exposed by the removal of the smear layer, surfaces devoid of the debris normally present in root planed‐only specimens, and the dense network of collagen fibers that make up the dentin structure. Although differences were seen in surface depressions and fiber‐like structures among some specimens, the tetracycline HCl and citric acid solutions produced comparable morphologic characteristics. J Periodontol 1993; 64:689–693.
The Role of the Host Response in Periodontal Disease Progression: Implications for Future Treatment Strategies
Authors: Van Dyke Thomas E. , Lester Mary Ann , Shapira Lior
Published: March 2012

In this paper, we review the relevant aspects of host responses in periodontal diseases as we understand them today. Discussion will focus on neutrophil function, lymphocytes and the immune response, macrophage function, cytokines and complement, fibroblasts and growth factors, and regeneration. Recent literature and concepts will be presented with an emphasis on future directions and application to treatment regimens. J Periodontol 1993; 64:792–806.
The Effects of Incubation Length and Temperature on the Specificity and Sensitivity of the BANA (N‐Benzoyl‐DL‐Arginine‐Naphthylamide) Test
Authors: Amalfitano Joseph , De Filippo Anna B. , Bretz Walter A. , Loesche Walter J.
Published: March 2012

A previous multi‐center study examining patients diagnosed as having at least four periodontally diseased teeth showed that when BANA (N‐Benzoyl‐DL‐Arginine‐Naphthylamide) hydrolysis by periodontal pathogens such as Treponema denticela, Porphyromonas gingivalis, and Bacteroides forsythus was evaluated versus clinical parameters such as clinical judgment of disease, bleeding on probing, and pocket depth, the sensitivity of the test was 84%, 82%, and 87%, respectively, while the specificity was only 42%, 41%, and 32%, respectively. The purpose of the present investigation was to improve the specificity of the test while retaining a high level of sensitivity in both gingivally healthy and periodontally diseased groups. One hundred forty‐nine patients participated in this study providing 3,497 interproximal plaque samples. Gingival health was measured using the papillary bleeding score and this was compared with the presence or absence of detectable trypsin‐like activity, as determined by the BANA hydrolysis of interproximal plaque samples, using a commercially‐available test. Sensitivity and specificity were measured by varying the incubation time and temperature of the enzymatic assay. Using the correlated binomial model to analyze site‐specific data within a patient, the specificity was highest at 35°C and 5 minutes incubation (94%), and lowest at 45°C and 15 minutes incubation (33%). Sensitivity was highest at 45°C or 55°C and 15 minutes incubation (90%) and lowest at 35°C and 5 minutes incubation (47%). When the sensitivity and specificity of the test run at 35°C for 5 minutes were used in a model for a diagnostic test proposed by Douglass and Fox, the test has utility when used on older general dental patients and for periodontal patients. J Periodontol 1993; 64:848–852.