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Peri-implant squamous cell carcinoma is an uncommon pathological manifestation, whereas peri-implantitis is commonly found in association with dental implants. Both present similarly with loss of supporting soft and hard tissue around dental implants; therefore, a careful differential diagnosis is required. The present case concerns a 62-year-old Japanese man who had a dental implant which had been in the left maxillary incisor region for 4 years who apparently developed peri-implantitis. This did not respond to localized therapy and antibiotics so was referred for specialist surgical management. A biopsy confirmed it to be a squamous cell carcinoma rather than an inflammatory lesion. A literature review shows that this is an unusual presentation without a previous history of malignancy, mucosal disease or risk factors for cancers. Although rare, the possibility of peri-implant squamous cell carcinoma should be borne in mind by all practitioners who monitor implant patients. [ABSTRACT FROM AUTHOR]

SUMMARY Most topology optimization problems are formulated as constrained optimization problems; thus, mathematical programming has been the mainstream. On the other hand, solving topology optimization problems using time evolution equations, seen in the level set-based and the phase field-based methods, is yet another approach. One issue is the treatment of multiple constraints, which is difficult to incorporate within time evolution equations. Another issue is the extra re-initialization steps that interrupt the time integration from time to time. This paper proposes a way to describe, using a Heaviside projection-based representation, a time-dependent diffusion equation that addresses these two issues. The constraints are treated using a modified augmented Lagrangian approach in which the Lagrange multipliers are updated by simple ordinary differential equations. The proposed method is easy to implement using a high-level finite element code. Also, it is very practical in the sense that one can fully utilize the existing framework of the code: GUI, parallelized solvers, animations, data imports/exports, and so on. The effectiveness of the proposed method is demonstrated through numerical examples in both the planar and spatial cases. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

BACKGROUND: In this study, we analyzed the gene expression profile of fibroblast-like synoviocyte (FLS) cultures from the temporomandibular joint (TMJ) to identify candidate genes associated with intracapsular pathologic conditions of TMJ. Cyclooxygenase (COX)-2 was one of the genes in FLS upregulated following stimulation by interleukin (IL)-1beta, a cytokine thought to play a key role in several pathological conditions. This study investigated the expression of COX-1 and COX-2 in cultured human FLS and rat TMJ synovium following stimulation with IL-1beta. METHODS: RNA was isolated from human FLS after IL-1beta treatment. COX-1 and -2 expression was examined using a GeneChip and real-time polymerase chain reaction. Prostaglandin E(2) (PGE(2)) levels in conditioned media from FLS were measured using enzyme-linked immunosorbent assay. Synovial tissues from TMJs of IL-1beta-injected rats were examined for COX-1 and COX-2 expression by immunohistochemical staining. RESULTS: Following treatment of FLS with IL-1beta, expression of the COX-2 gene increased up to 8 h and peaked at 4 h, whereas COX-1 expression did not change. Stimulation with IL-1beta increased the level of PGE(2) in conditioned media of cultured FLS in a time-dependent manner up to 48 h. Immunohistochemistry showed a strong positive staining for COX-2 in the lining and sub-lining synovial tissues of the TMJ of IL-1beta-injected rats. In contrast, staining for COX-1 was the same in synovial tissues with and without IL-1beta injection. CONCLUSION: These data suggest that COX-2 expression stimulated by IL-1beta stimulates the production of PGE(2) in FLS and plays important roles in the progression of inflammation in TMJ. [ABSTRACT FROM AUTHOR]

Background: To understand the immunopathological features of oral lichen planus (OLP), we analyzed the expression of chemokines in the epithelial cell layers.Methods: Epithelia from OLP or healthy gingiva were collected by laser microdissection. The chemokine and chemokine receptor expressions in the epithelia were analyzed by DNA microarray.Results: High levels of MIP-3 alpha /LARC/CCL20 and its receptor CCR6 were expressed in the lesional epithelia. Furthermore, DC-CK1/CCL18, ELC/CCL19, SDF-1/CXCL12 and CXCR4 expressions were also increased. Immunohistologial analysis showed that high numbers of Langerhans cells (LCs) were present in the epithelia of OLP. Lesional epithelia also expressed high levels of the ligands specific for CXCR3 (e.g. MIG/CXCL9, IP-10/CXCL10 and I-TAC/CXCL11) and CCR5 (e.g. RANTES/CCL5).Conclusions: Infiltration of LCs is orchestrated by CCR6. Further, LCs residing in the lesional epithelia may be a mature phenotype. Moreover, infiltration of T cells in OLP could be mediated by signaling pathways through CXCR3 and CCR5. [ABSTRACT FROM AUTHOR]

Synovial fibroblasts of temporomandibular joint (TMJ) are poorly characterized, although they have important roles in progression of temporomandibular disorders (TMD). In this study, we investigated responses of synovial fibroblasts to interleukin (IL)-1β.We examined gene expression profiles of synovial fibroblasts in response to IL-1β, using Affymetrix GeneChip. Regulated upon activation normal T-cell expressed and secreted (RANTES) gene expression was confirmed by polymerase chain reaction (PCR) and real-time PCR. RANTES protein levels were measured by enzyme-linked immunosorbent assay (ELISA).The RANTES was preferentially up-regulated in synovial fibroblasts by IL-1β. The increase in RANTES gene expression in response to IL-1β was confirmed by PCR and real-time PCR. Protein level of RANTES in synovial fibroblasts was also increased by IL-1β.The RANTES, a cc-type chemokine, has chemotactic effects on lymphocytes and monocytes. Increased gene expression and protein production of RANTES in synovial fibroblasts, in response to IL-1β, may play an important role in recruitment of inflammatory cells into synovium and progression of synovitis in TMD.J Oral Pathol Med(2004)33: 629–33 [ABSTRACT FROM AUTHOR]

PKN is a fatty acid- and Rho-activated serine/threonine kinase, which has a catalytic domain highly homologous to that of protein kinase C (PKC). Recent studies have demonstrated that PKN is proteolytically cleaved after apoptotic stimulation and then a constitutively active 55-kDa fragment is generated. However, the role of the 55-kDa fragment are poorly understood. Adult Sprague–Dawley (SD) rats underwent middle cerebral artery occlusion (MCAO), and the temporal and spatial changes in the fragmentation of PKN and of PKC δ were examined by immunoblotting. No proteolytic fragment of PKC δ (about 40 kDa) was detected. The 55-kDa fragment of PKN appeared transiently from 3 days after MCAO at the ipsilateral normal cortex. At the boundary zone of infarction, the 55-kDa fragment was markedly induced from day 5 then peaked on day 21 and persisted until day 28. Analysis of anti-phosphoserine immunoprecipitates with an anti-PKN antibody revealed phosphorylation of the 55-kDa band. Double staining for PKN and Ox42 was used to examine the source of the 55-kDa fragment. PKN immunoreactivity was significantly increased in Ox42-positive cells (microglia/hematogenous macrophages). No DNA laddering and only a few terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-positive cells were observed on day 14 in despite of the high level appearance of the 55-kDa band. These results suggest that the constitutively active 55-kDa fragment of PKN does not contribute to apoptosis, but may contribute to a function of microglia/macrophages. [ABSTRACT FROM AUTHOR]

Discusses the cases of patients with distal chromosome 15q deletion. Clinical manifestations of intrauterine growth retardation; Pre- and post-natal growth retardation; In situ hybridization analysis.

Partial 1q trisomy syndrome is a rare disorder. Because unbalanced chromosomal translocations often occur with 1q trisomy, it is difficult to determine whether patient symptoms are related to 1q trisomy or other chromosomal abnormalities. The present study evaluated genotype-phenotype correlations of 26 cases diagnosed with 1q partial trisomy syndrome. DNA microarray was used to investigate the duplication/triplication region of 16 cases. Although there was no overlapping region common to all 26 cases, the 1q41-qter region was frequently involved. One case diagnosed as a pure interstitial trisomy of chromosome 1q by G-banded karyotype analysis was instead found to be a pure partial tetrasomy by CytoScan HD Array. In four 1q trisomy syndrome cases involving translocation, the translocated partner chromosome could not be detected by DNA microarray analyzes despite G-banded karyotype analysis, because there were a limited number of probes available for the partner region. DNA microarray and G-banded karyotyping techniques were therefore shown to be compensatory diagnostic tools that should be used by clinicians who suspect chromosomal abnormalities. It is important to continue recruiting affected patients and observe and monitor their symptoms to reveal genotype-phenotype correlations and to fully understand their prognosis and identify causal regions of symptoms., (© 2016 Wiley Periodicals, Inc.)

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) have been widely used for the management of pain and inflammation. However, little remains known about the effects of NSAIDs on synovitis of the human temporomandibular joint (TMJ). The aims of this study were to investigate the potential anti-inflammatory effects of NSAIDs on synovitis of the TMJ and the inflammatory effects of PGE2 on fibroblast-like synoviocytes (FLS) derived from the TMJ., Methods: Human synovial tissue was obtained from patients with internal derangement who underwent arthroscopy of the TMJ. FLSs were prepared from the tissues using the outgrowth method. A COX inhibitor (indomethacin or celecoxib) was added to the IL-1β-stimulated cells in culture. The cells were also stimulated with PGE2 or an EP agonist. The PGE2 production and COX-2 and IL-6 expression levels were examined using enzyme-linked immunosorbent assays, real-time PCR, and a microarray analysis., Results: COX inhibitors decreased not only PGE2 production, but also the expression of COX-2 and IL-6 in FLS stimulated with IL-1β. EP2 and EP4 were both expressed in the FLS, and the treatment with EP2 and EP4 agonists induced IL-6 production in these cells., Conclusion: The COX inhibitors indomethacin and celecoxib reduce the expression of inflammatory factors, such as COX-2 and IL-6, in FLS from the TMJ via suppression of PGE2 production. EP2 and EP4 were the main receptors for PGE2 present in the FLS. The approach used in this study may be useful for revealing how drugs such as NSAIDs affect the cellular functions of FLS from the TMJ., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) are key mediators of the intracapsular pathological conditions of the temporomandibular joint (TMJ). Therefore, the gene expression profiles in synovial fibroblast-like cells (SFCs) from patients with internal derangement of the TMJ were examined after they were stimulated with IL-1β or TNF-α to determine which genes were altered., Methods: Ribonucleic acid was isolated from SFCs after IL-1β or TNF-α treatment. Gene expression profiling was performed using oligonucleotide microarray analysis. On the basis of the results of this assay, we investigated the kinetics of macrophage inflammatory protein-3α (MIP-3α) gene expression using PCR, and protein production in TMJ SFCs stimulated by IL-1β or TNF-α using an ELISA. Inhibition experiments were performed with MAPK and NFκB inhibitors. SFCs were stimulated with IL-1β or TNF-α after treatment with inhibitors. The MIP-3α levels were measured using an ELISA., Results: Macrophage inflammatory protein-3α was the gene most upregulated by IL-1β- or TNF-α stimulation. The mRNA and protein levels of MIP-3α increased in response to IL-1β in a time-dependent manner. In contrast, during TNF-α stimulation, the MIP-3α mRNA levels peaked at 4 h, and the protein levels peaked at 8 h. In addition, the IL-1β- and TNF-α-stimulated MIP-3α production was potently reduced by the MAPK and NFκB signaling pathway inhibitors., Conclusion: Interleukin-1β and TNF-α increased the MIP-3α production in SFCs via the MAPK and NFκB pathways. These results suggest that the production of MIP-3α from stimulation with IL-1β or TNF-α is one factor associated with the inflammatory progression of the internal derangement of the TMJ., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Acquired aplastic anaemia (aAA) is recognized as an autoimmune disorder; however, the autoantigens and target cells involved remain elusive. Expression of autoantibodies and their target cells were examined using the haematopoietic cell line K562 and bone marrow stromal cell line hTS-5; 43·5% and 21·7% of aAA expressed autoantibody against K562 and hTS-5 cells, respectively. The autoantigens were identified by serological identification of antigens through recombinant cDNA expression cloning. This study indicates that haematopoietic cells are the targets of immune abnormality in aAA. These autoantibodies may be utilized to distinguish patients associated with immune abnormality from bone marrow failure syndrome., (© 2012 Blackwell Publishing Ltd.)

Background: Interleukin (IL)-1beta is thought to play a key role in several pathologic conditions of the temporomandibular joint (TMJ). Gene expression profile of synovial fibroblasts stimulated with IL-1beta was studied by oligonucleotide microarray analysis to elucidate candidate genes associated with intracapsular pathologic conditions of TMJ., Methods: RNA was isolated from synovial fibroblasts from five patients after IL-1beta treatment. Gene expression profiling was performed with a GeneChip. Changes in gene expression were determined by comparing IL-1beta-treated cells with untreated cells., Results: A total of 121 genes showed a greater than threefold difference in average intensity between untreated and IL-1beta-treated synovial fibroblasts in five experiments. Five chemokines were among the 10 most upregulated genes, and the most upregulated gene was CCL20. The 121 IL-1beta-responsive genes included 12 chemokines whose mRNA levels were confirmed by real-time PCR., Conclusion: These data should provided useful information about the pathologic conditions of TMJ, especially in support of diagnosis and therapeutic approaches to TMJ.

The purpose of this study was to know a role of confined placental mosaicism (CPM) in perinatal outcome and postnatal growth and development of infants with intrauterine growth restriction (IUGR). We selected 50 infants with IUGR (<-2.0 SD) from 3,257 deliveries in a regional medical center during the past 10-year period, and carried out cytogenetic and molecular analyses in their placenta and cord blood. Of the 50 infants, 8 had CPM (CPM group) and were composed of five single (CPM2, 7, 13, 22, and 22), one double (CPM7/13), and one quadruple trisomy (CPM2/7/15/20), and one partial monosomy [del(2)(p16)]. The origin of an extra chromosome of trisomy was maternal in six cases of CPM, paternal in one, and undetermined in one. Uniparental disomy in disomic cell lines was ruled out in all these mosaics. We also compared clinical parameters for perinatal outcome between CPM group and infants without evidence of CPM (non-CPM group), such as maternal and gestational age, birth weight, Apgar score, cord blood pH, gender, and uterine artery patterns by Doppler ultrasonography, as well as weight, height, and developmental quotient (DQ) by Denver Developmental Screening Test at age 12 months. Phenotypic abnormalities were noted in two infants with CPM and three infants of non-CPM group: One with CPM22 had ASD and hypospadias, one with CPM7/13 had Russell-Silver syndrome (RSS), and one without CPM had polydactyly, and two without CPM had RSS. All but one infant with CPM are alive at age 12 months. Among the clinical parameters, the detection rate of a notch waveform pattern of the uterine artery was significantly higher in the CPM group (P < 0.05). However, no significant difference was noted in perinatal outcome of pregnancy and in DQ at age 12 months between the two groups. Interestingly, short stature (<-2 SD) at age 12 months was more frequently seen in CPM group (7/8 infants with CPM vs. 8/15 infants without CPM), although no statistically significant difference was obtained. The information obtained will be useful for perinatal care and genetic counseling for infants with IUGR and CPM.

In order to evaluate the contribution of FBN1, FBN2, TGFBR1, and TGFBR2 mutations to the Marfan syndrome (MFS) phenotype, the four genes were analyzed by direct sequencing in 49 patients with MFS or suspected MFS as a cohort study. A total of 27 FBN1 mutations (22 novel) in 27 patients (55%, 27/49), 1 novel TGFBR1 mutation in 1 (2%, 1/49), and 2 recurrent TGFBR2 mutations in 2 (4%, 2/49) were identified. No FBN2 mutation was found. Three patients with either TGFBR1 or TGFBR2 abnormality did not fulfill the Ghent criteria, but expressed some overlapping features of MFS and Loeys-Dietz syndrome (LDS). In the remaining 19 patients, either of the genes did not show any abnormalities. This study indicated that FBN1 mutations were predominant in MFS but TGFBRs defects may account for approximately 5-10% of patients with the syndrome.

Background: Synovitis, which is characterized by infiltration of inflammatory cells, often accompanies progression of clinical symptoms of the temporomandibular joint (TMJ). Synovial fibroblasts of the TMJ are believed to play important roles in progression of synovitis. The purpose of this study was to examine production and gene expression of chemokines by synovial fibroblasts stimulated by tumor necrosis factor-alpha (TNF-alpha)., Methods: Protein levels of chemokines were measured by enzyme-linked immunosorbent assay (ELISA). Gene expression of chemokines was analyzed by real-time polymerase chain reaction (PCR)., Results: Production of interleukin (IL)-8, growth-related oncogene (GRO)-alpha, monocyte chemoattractant protein (MCP)-1, and regulated upon activation normal T-cell expressed and secreted (RANTES) protein by synovial fibroblasts was increased by TNF-alpha. In contrast, stromal cell-derived factor (SDF)-1alpha, macrophage inflammatory protein (MIP)-1alpha and -1beta were not detectable in conditioned media of synovial fibroblasts, with or without TNF-alpha treatment. Increases in gene expression of IL-8, GRO-alpha, MCP-1, and RANTES in response to TNF-alpha treatment were detected., Conclusions: Increased protein production and gene expression of chemokines by synovial fibroblasts in response to TNF-alpha treatment appears to play an important role in recruitment of inflammatory cells into synovium and the progression of synovitis in the TMJ.

We analyzed five patients with inverted duplication deletion of 8p [inv dup del(8p)] using fluorescence in situ hybridization (FISH) and short tandem repeat polymorphism (STRP) analysis. In all patients, inv dup del(8p) consisted of a deleted distal segment, an intact in-between segment, and a duplicated proximal segment. In all of them, the proximal breakpoint of the deletion and one of the breakpoints of the duplication were identical, each located at one of the two olfactory receptor gene clusters at 8p23. FISH analysis showed all their mothers to be heterozygous carriers of an 8p23 inversion [inv(8)(p23)]. STRP analysis indicated that the deletions occurred in maternally derived chromosomes. The duplicated segments had two copies of maternal, either heterozygous or homozygous alleles. These findings support and reinforce those in 16 patients with inv dup del(8p) and their parents by Floridia et al. [1996: Am J Hum Genet 58:785-796] and subsequent additional studies of 10 of them by Giglio et al. [2001: Am J Hum Genet 68:874-883]. Based on these findings, we propose a model for the inv dup del(8p) formation. The inverted segment and its normal counterpart in inv(8)(p23) heterozygous carrier mothers form a loop at the pachytene period of meiosis I. Inv dup del(8p) with heterozygous duplication is formed through at least one meiotic recombination within the loop. Inv dup del(8p) with the homozygous duplication arises through two meiotic recombinations on the inv(8)(p23) chromosome (one within the loop and the other between the loop and centromere). Subsequent rescue by eliminating a part of the duplicated segment and a centromere enables formation of viable inv dup del(8p). The frequency of the inv(8)(p23) allele is 39% in a normal Japanese population, comparable to 26% in Europeans Giglio et al. [2001: Am J Hum Genet 68:874-883]. The proposed mechanism of formation of inv dup del(8p) requires two independent events (a recombination within the loop and subsequent rescue), which may explain its rarity., (Copyright 2004 Wiley-Liss, Inc.)

We report on a 3-year-old boy with circumferential skin creases as seen in Michelin tire baby syndrome (MTBS), hearing impairment, undescended testes, short stature, and mental handicap. Skin biopsy from the inguinal region showed degenerative collagen, which has never been found in MTBS. Similar clinical manifestations shared by our patient and a boy reported previously suggest a new clinical entity, in which degenerative collagen is etiologically involved. We propose an acronym to designate it: hearing impairment, undescended testis, circumferential skin creases, and mental handicap (HITCH) syndrome., (Copyright 2003 Wiley-Liss, Inc.)

Taxol is an effective anti-tumour drug against a variety of tumour cells. Taxol directly induces apoptosis in addition to a G2/M cell cycle arrest. However, it remains poorly understood how Taxol induces apoptosis in tumour cells. Taxol induces the secretion of inflammatory cytokines in murine macrophages in a toll-like receptor-4 (TLR-4)-dependent manner in addition to its anti-tumour effects, but the effect of Taxol on human macrophages is controversial. In this study, we demonstrated that low doses (less than 1000 nmol/l) of Taxol induced the expression of tumour necrosis factor (TNF)-alpha in human myelomonocytic cells and that the induction of TNF-alpha mRNA was inhibited by dominant-negative myeloid differentiation protein (dnMyD88). Furthermore, we demonstrated that the same doses of Taxol induced apoptosis of the same myelomonocytic cells and that the Taxol-induced apoptosis was also inhibited by dnMyD88. In accordance with the previous reports, Taxol induced the expression of TNF-alpha and apoptosis in a TLR4-independent manner. These results suggest that TNF-alpha expression and apoptosis, both induced by Taxol in human myelomonocytic cells, share the signal transduction molecule MyD88.

A practical on-line lymphocytapheresis (LCP) system using a leukapheresis filter (Cellsorba, Asahi Medical Co.) was evaluated in six patients with refractory rheumatoid arthritis. This filter consists of nonwoven fine polyester fiber wound around a porous cylinder. The blood was passed through the polyester fiber at a flow rate of 50 ml/min for 60 min. LCP was carried out once a week in the first month and biweekly in the next 2 months. An average of 98% of the leukocytes that entered the filter (1.27 x 10(10) cells) and 100% of the lymphocytes that entered the filter (3.66 x 10(9) cells) were removed in the first LCP. A total of 96.6% of the platelets and 2.7% of the erythrocytes that entered the filter were also removed. All of the patients showed clinical improvement in morning stiffness, Lansbury articular index, and functional capacity, with no adverse reaction. The number of circulating erythrocytes and platelets and the concentration of various serum components showed no significant change during the treatments. This LCP system required no fresh frozen plasma, albumin, or other blood transfusion. The number of circulating lymphocytes decreased to 65-70% of the pretreatment circulating lymphocyte count at the last procedure, with a decrease in the ratio of Leu3a positive cells to Leu2a positive cells. The proliferative response to phytohemagglutinin and concanavalin A was improved. These data suggest that LCP to remove approximately 3 x 10(9) lymphocytes once a week or biweekly has an immunomodulatory effect.