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Cell adhesion molecule 1 (CADM1) is aberrantly expressed by T-cell neoplasms such as adult T-cell leukemia/lymphoma (ATLL) and mycosis fungoides (MF). We studied the expression of CADM1 and its splicing variants in Sézary syndrome (SS), MF, other cutaneous T-cell lymphoma (CTCL), and cell lines derived from T- and B-cell lymphomas. Soluble CADM1 was measured in the patients' sera. CADM1+ cells in the blood and skin lesions were examined by flow cytometry and immunostaining, respectively. Soluble CADM1 was measured by ELISA, and the splicing variants of CADM1 transcripts were determined by reverse transcriptase-polymerase chain reaction, followed by sequencing. As a result, circulating CADM1+ cells were significantly increased in seven out of 10 patients with SS, ranging from 7.9% to 74.5% of the CD3+CD4+ fractions (median 33.7%; cut-off value 6.5%). The percentages of CADM1+ cells were usually less than those of circulating Sézary cells. CADM1 was expressed, to various degrees, in six of nine T-cell lines derived from SS, MF, ATLL, and anaplastic large cell lymphoma (ALCL), but negative in B-cell lymphoma-derived cell lines. CADM1+ cells were present in the skin infiltrates of MF, SS, ATLL and ALCL. Serum levels of soluble CADM1 were not significantly elevated in SS/MF. Three major splicing variants of CADM1 expressed by neoplastic T-cells contained different combinations of the exons 7, 8, 9 and 11, including a putative oncogenic variant composed of exons 7-8-9-11. In conclusion, CADM1 is frequently expressed in Sézary cells and cell lines from CTCL.

Positron emission tomography (PET) is used for staging and response evaluation in primary gastric lymphoma (PGL). However, the implications of [(18)F]-2-fluoro-2-deoxy-D-glucose ((18)F-FDG) uptake in PGL at first diagnosis have not been reported. The relationship between (18)F-FDG uptake and the expression of facilitative glucose transporters (GLUTs), hexokinase II (HK II), and Ki67, as well as malignant potential in PGL, was assessed in this study. We analyzed 23 patients with PGL [nine with diffuse large B-cell lymphoma (DLBCL); seven with high-grade mucosa-associated lymphoid tissue (MALT) lymphoma; and seven with low-grade MALT lymphoma]. The expression levels of GLUT1, GLUT3, HK II, and Ki67 were evaluated according to the percentage of positive area determined by immunohistochemistry. Standardized uptake values correlated significantly with pathological malignant potentials (low-grade/high-grade MALT lymphoma and DLBCL: p = 0.001-0.002), Ki67 (p 0.001), and GLUT1 expression (p = 0.02). We determined that (18)F-FDG uptake is related to GLUT1 expression and tumor histological grade as well as Ki67 in PGL.

Sensitization of primary afferent neurons is one of the most important components of pain hypersensitivity after tissue injury. Insulin-like growth factor 1 (IGF-1), involved in wound repair in injured tissue, also plays an important role in maintaining neuronal function. In the present study, we investigated the effect of tissue IGF-1 on nociceptive sensitivity of primary afferent neurons. Local administration of IGF-1 induced thermal and mechanical pain hypersensitivity in a dose-dependent manner, and was attenuated by IGF-1 receptor (IGF1R) inhibition. Tissue but not plasma IGF-1 levels, as determined by enzyme-linked immunosorbent assay, significantly increased after plantar incision. Immunohistochemistry revealed that IGF1R was predominantly expressed in neurons as well as in satellite glial cells in the dorsal root ganglion (DRG). Double-labeling immunohistochemistry showed that IGF1R expression colocalized with peripherin and TRPV1, but not with NF200 in DRG neurons. The IGF1R inhibitor successfully alleviated mechanical allodynia, heat hyperalgesia, and spontaneous pain behavior observed after plantar incision. Expression of phosphorylated Akt in DRG neurons significantly increased after plantar incision and was suppressed by IGF1R inhibition. These results demonstrate that increased tissue IGF-1 production sensitizes primary afferent neurons via the IGF1R/Akt pathway to facilitate pain hypersensitivity after tissue damage.

Porphyromonas gingivalis is considered a critical pathogen of periodontal diseases including recurrent periodontitis. The profound effects of active periodontal treatment (APT) on P. gingivalis elimination were previously demonstrated and revealed that the subsequent P. gingivalis-free or -suppressed status seems to be maintained during early periodontal maintenance (PMT). The aim of the present study was to show the occurrence of microbial recolonization during this early PMT period.In total, 128 sites from 11 generalized chronic periodontitis patients and one generalized aggressive periodontitis patient underwent clinical and microbiologic examination at baseline (Exam-I), after APT (Exam-II), and in PMT (Exam-III). Exam-III was carried out an average of 4.5 +/- 3.5 months after Exam-II. Detection and quantification of putative pathogens were performed using a polymerase chain reaction-based method.The PMT used was effective in maintaining the clinical conditions improved by APT. However, in microbiological examinations, Exam-III showed higher detection frequency and levels of P. gingivalis than Exam-II. This suggests that a P. gingivalis recolonization started in the early PMT period. P. gingivalis-increased sites then showed significantly more severe signs of periodontitis in Exam-I than P. gingivalis-stable sites (bleeding on probing frequency: 76.7% versus 56.5%; suppuration frequency: 41.9% versus 12.9%). On the other hand, in Exam-II, no significant differences of clinical parameters were noted between P. gingivalis-increased and -stable sites.Severe periodontitis sites before APT seemed to place them at risk of P. gingivalis recolonization in the early PMT period, and this microbial restoration could be a cause of recurrent periodontitis.

Porphyromonas gingivalis is considered a critical pathogen in periodontal diseases. It is classified into six genotypes based on diversity of the fimA gene encoding fimbrillin. The present study evaluated the involvement of the fimA genotype in treatment outcome following non-surgical periodontal therapy.Chronic periodontitis patients were enrolled in this study; all received clinical and microbiological examinations at baseline. The detection of subgingival species and identification of P. gingivalis fimA genotypes were performed using polymerase chain reaction based methods. In total, 160 P. gingivalis positive sites with bleeding on probing (BOP) and a probing depth ofor =4 mm were accepted. They were followed up after scaling and root planing.Longitudinal investigation indicated that fimA type I positive sites at baseline were followed by a significantly higher frequency of persistent BOP after treatment than type I negative sites (51.6% versus 27.9%), while types Ib and II were not. Type I positive sites also showed more persistence of Tannerella forsythensis and P. gingivalis after treatment than type I negative sites. In post-treatment investigation, type I positive sites showed higher frequencies of BOP and T. forsythensis detection than type I negative sites (77.8% versus 43.5% and 100% versus 76.1%, respectively).BOP in initially type I positive sites showed little improvement with treatment, and the combined persistence of fimA type I and T. forsythensis seemed to be involved in this poor treatment outcome. The present study demonstrated the potential of P. gingivalis fimA type I as a predictor of persistent BOP after treatment.

Background: The fimA gene, which encodes fimbrillin (FimA), is found in Porphyromonas gingivalis and has been classified into six genotypes based on nucleotide sequence. P. gingivalis that possesses the type II fimA gene is prevalent in adult periodontitis. Objectives: The aim of this study was to investigate the prevalence of P. gingivalis fimA genotypes in Japanese aggressive periodontitis patients, and to examine their virulence. Methods: Subgingival plaque samples were obtained from 223 sites in 18 aggressive periodontitis patients and 95 sites in 22 periodontally healthy young adults. Actinobacillus actinomycetemcomitans, P. gingivalis and Tannerella forsythensis detection, determination of the fimA genotype in P. gingivalis, and the quantification of P. gingivalis were analyzed by polymerase chain reaction (PCR) methods. The proteolytic activities of the P. gingivalis fimA type I and fimA type II were also examined. Results: In aggressive periodontitis patients, the most prevalent fimA genotype was the type II (46.7%), followed by the type Ib and type I, whereas in healthy subjects, the type I fimA was the only genotype detected. The number of P. gingivalis pathogens was the greatest in the type I fimA positive sites, and the frequency of coexisting A. actinomycetemcomitans and T. forsythensis was highest in the type II fimA positive sites in the aggressive periodontitis patients. Both the arginine-specific cysteine proteinase (Arg-gingipain) and lysine-specific cysteine proteinase (Lys-gingipain) activity of the P. gingivalis fimA type I strain were significantly higher than those of the fimA type II strains. Conclusions: These results suggest that differences in virulence exist among different fimA genotypes. Coadherence with other pathogens in P. gingivalis fimA type II-associated aggressive periodontitis and quantitative increases in P. gingivalis in fimA type I-associated aggressive periodontitis are related to this virulence.

Background Azithromycin is an antibiotic belonging to the macrolides. Previous case reports showed that azithromycin has a regenerative effect on periodontal tissue in addition to improving periodontal gingival inflammation. Recently, we experienced three periodontitis cases, all of which showed severe bone loss. However, their gingival inflammatory signs differed greatly. The present case reports evaluated the regenerative effects of azithromycin on periodontitis sites with different clinical signs of gingival inflammation. Methods In Case 1, generalized chronic periodontitis with severe gingival inflammation was treated with azithromycin before periodontal treatment. In contrast, Case 2 presented with few clinical signs of gingival inflammation, but was treated with azithromycin prescribed within a day of scaling and root planing. In Case 3, teeth with moderate gingival inflammation were treated with azithromycin after a series of scaling and root planing. Results Remarkable alveolar bone growth, regardless of baseline gingival inflammation, was noted in all three cases. Conclusions The use of adjunctive azithromycin in scaling and root planing may be effective for periodontal tissue regeneration. This property may be independent of the degree of baseline gingival inflammation.

Background The phosphorylation of p38 mitogen-activated protein kinase (MAPK) in the dorsal root ganglion (DRG) promotes primary afferent sensitization. The role of p38MAPK signaling in the DRG in the pathogenesis of plantar incision hyperalgesia has not been investigated. Results Levels of phosphorylated p38MAPK (p-p38MAPK) obviously increased in the DRG after plantar incision. Unmyelinated and myelinated DRG neurons that express p-p38MAPK contained small to medium cell bodies, suggesting that p-p38MAPK expression is induced in neurons with C- and Aδ-fibers. The p-p38MAPK inhibitors FR167653 or SB203580 inhibited incision-induced mechanical hypersensitivity and spontaneous pain behavior. The systemic administration of tumor necrosis factor-α (TNF-α) inhibitor prevented subsequent incision-induced activation of p38MAPK in the DRG and alleviated mechanical hypersensitivity after the incision. Conclusions p38MAPK signaling in the DRG plays a crucial role in the development of primary afferent sensitization and pain behavior caused by plantar incision.

Pro-inflammatory cytokine high mobility group box-1 (HMGB-1) is involved in inflammation in the central nervous system, but less is known about its biological effects in the peripheral nervous system. In the present study, the role of HMGB-1 in the primary afferent nerve was investigated in the context of the pathophysiology of peripheral nerve injury-induced pain hypersensitivity. Real-time PCR confirmed an increase in HMGB-1 mRNA expression in the dorsal root ganglion (DRG) and spinal nerve at 1 day after spinal nerve ligation (SNL). Induction of HMGB-1 mRNA was observed in both injured L5 and uninjured L4. Immunohistochemistry for HMGB-1 revealed that SNL-induced HMGB-1 expression in the primary afferent neurons and satellite glial cells (SGCs) in the DRG, and in Schwann cells in the spinal nerve. Up-regulation of HMGB-1 was associated with translocation of its signal from the nucleus to the cytoplasm. Injection of HMGB-1 into the sciatic nerve produces transient behavioural hyperalgesia. Neutralizing antibody against HMGB-1 successfully alleviated the mechanical allodynia observed after SNL treatment. Receptor for advanced glycation end products (RAGE), one of the major receptors for HMGB-1, was expressed in the primary afferent neurons and SGCs in the DRG, as well as in Schwann cells in the spinal nerve. These results indicate that HMGB-1 is synthesized and secreted into the DRG and spinal nerve, and contributes to the development of neuropathic pain after nerve injury. Blocking HMGB-1/RAGE signalling might thus be a promising therapeutic strategy for the management of neuropathic pain.

Bacteroides forsythus is one of the important periodontopathic bacteria, and this microorganism is known to have an S-layer outside the outer membrane. The S-layer-like antigens were recently isolated from B. forsythus , and they were found to be 270- and 230-kDa proteins in the envelope fraction. In this study, these proteins were confirmed to be specific to B. forsythus by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and they were clearly recognized by sera from patients with adult and early-onset periodontitis in Western immmunoblot analysis. We compared the immunoglobulin G (IgG) responses against the purified S-layer-like antigen by enzyme-linked immunosorbent assay. IgG responses against this antigen were low in healthy control subjects, but they were significantly higher in subjects with adult and early-onset periodontitis. Together with the fact that the IgG responses against the crude extract of B. forsythus did not rise significantly in patients with periodontitis, S-layer-like proteins are considered to be specific antigens of B. forsythus and may play an important role in the progression of periodontitis.

We reviewed the clinical records of 62 patients with voice disorders without organic diseases of the larynx who were examined in the Department of Otolaryngology, Kurume University Hospital during the 10 years from 1971 to 1980. There were 9 patients with psychogenic dysphonia, 24 with vocal abuse, 4 with spastic dysphonia, 9 with mutational voice disturbance, 8 with virilization of voice, 7 with dysphonia attributed to diseases of other organs than the larynx, and 1 with senile change of voice. The clinical service to the patients with these kinds of dysphonia has been poor in Japan for lack of trained voice pathologists. This has been also the case with our department. Recognition for the necessity of voice pathologists is strongly demanded.