High frequency of upper aerodigestive tract manifestations in mucous membrane pemphigoid.

OBJECTIVE: The objective of this study was to evaluate the frequency of upper aerodigestive tract involvement in patients with mucous membrane pemphigoid associated with desquamative gingivitis. SUBJECTS AND METHODS: Data from 25 patients were collected by retrospective chart review. Their upper aerodigestive had been evaluated using a conventional flexible fiberscope. Oral disease activity was quantified on the basis of the Mucous Membrane Pemphigoid Disease Area Index activity score. RESULTS: Lesions of the upper aerodigestive tract were confirmed in nine symptomatic patients (9/25, 36%), of which five (5/25, 20%) had laryngeal involvement. No lesions were seen in the asymptomatic patients on fiberscope examination. There was a statistically significant difference in the symptoms, high oral disease activity score, and linear IgA deposition on direct immunofluorescence between patients with and without upper aerodigestive tract lesions (p = .001, .001, .002, respectively). CONCLUSION: The high frequency of considerable complications highlights the importance of confirming the presence of upper aerodigestive tract involvement in patients with mucous membrane pemphigoid having desquamative gingivitis. Signs including the presence of symptoms, high oral disease activity score, or linear IgA deposition on direct immunofluorescence might indicate a higher risk of upper aerodigestive tract involvement.

Assessment of Screening for Nasal Obstruction among Sleep Dentistry Outpatients with Obstructive Sleep Apnea.

Oral appliances (OA), a common treatment modality for obstructive sleep apnea (OSA), are not suitable for patients with nasal obstruction. Rhinomanometry, the gold standard technique to assess nasal airway resistance, is not readily available in sleep dentistry clinics. We demonstrate the use of a portable lightweight peak nasal inspiratory flow (PNIF) rate meter to objectively assess nasal airflow and utilized the Nasal Obstruction Symptom Evaluation (NOSE) scale to subjectively assess nasal obstruction in 97 patients with OSA and 105 healthy controls. We examined the correlations between the following variables between the groups: demographics, body mass index, PNIF, NOSE scale scores, apnea-hypopnea index (AHI), minimum SpO2 (SpO2min), Mallampati classification, and Epworth Sleepiness Scale (ESS) scores. Patients with OSA had significantly lower PNIF values and higher NOSE scores than controls. In the patient group, PNIF was not significantly correlated with AHI, SpO2min, Mallampati classification, or NOSE or ESS scores. Lower PNIF values and higher NOSE scores suggested impaired nasal airflow in the OSA group. As daytime PNIF measurement bears no relationship to AHI, this cannot be used alone in predicting the suitability of treatment for OSA with OA but can be used as an adjunct for making clinical decisions.

Acantholysis may precede elevation of circulating anti-desmoglein 3 antibody levels in pemphigus vulgaris presenting with desquamative gingivitis.

Pemphigus vulgaris (PV) is an autoimmune, blistering disease that affects the mucosa and skin. The current theory favors the concept that anti-desmoglein (Dsg) 3 autoimmunity is the only pathogenic event needed to induce acantholysis. However, a few cases of active PV in the oral cavity had no detectable anti-Dsg 3 antibody. The aim of this study was to evaluate the differences in clinical and laboratory findings, whether or not the anti-Dsg 3 antibodies were present. This study was based on a retrospective review of 10 PV cases. The evaluation of the circulating autoantibody titers to Dsg 3 was conducted by using enzyme-linked immunosorbent assay (ELISA). An index value of 20 or more was used as the cutoff for a positive reaction. Only five of the 10 PV cases had a positive Dsg 3 ELISA. There were no differences in clinical, cytological, histopathological, and direct immunofluorescence findings, whether or not the anti-Dsg 3 antibodies were present. Of the five patients with a negative reaction at the time of diagnosis, the Dsg 3 ELISA became positive in the follow-up period in three cases. In the remaining two cases, the Dsg 3 ELISA was consistently negative for 18 months. Dsg 3 ELISA was negative early in some PV cases. Therefore, PV acantholysis may precede the elevation of circulating anti-Dsg 3 antibody levels. The diagnosis of PV should be considered based on comprehensive clinical, histopathological, and immunofluorescent criteria.

A Case of Laryngeal Granuloma Likely Caused by Laryngopharyngeal Reflux Disease Following a Sagittal Split Ramus Osteotomy.

Laryngeal granuloma is an uncommon complication of prolonged endotracheal intubation. A 25-year-old woman with severe jaw deformity underwent sagittal split ramus osteotomy under general anesthesia. Two days after extubation, the patient complained of hoarseness, sore throat, and dyspnea. When symptoms persisted, she was evaluated in the Otolaryngology Department. She was diagnosed with laryngeal granuloma of the bilateral arytenoid cartilages, and conservative treatment was selected. Administration of corticosteroid hormones, proton pump inhibitors, and a subsequent follow-up examination performed in our outpatient clinic showed no evidence of recurrence 10 months after the initial presentation.

Characteristics of middle-aged and older patients with temporomandibular disorders and burning mouth syndrome.

The aim of this study was to evaluate the relationship between pain intensities and psychosocial characteristics in middle-aged and older patients with temporomandibular disorders (TMDs) and burning mouth syndrome (BMS). Subjects were selected according to the Research Diagnostic Criteria for TMD (n = 705) and International Association for the Study of Pain criteria for BMS (n = 175). Patients were then divided into two age groups: 45-64 years (middle-aged, Group A) and 65-84 years (older, Group B). Pain intensity and depression and somatization scores were evaluated in both groups. In BMS patients, present and worst pain intensities were significantly higher in Group B than in Group A {4.6 [95% confidence interval (CI) = 4.0-5.2] vs. 3.5 [95% CI = 3.1-3.9] and 5.9 [95% CI = 5.2-6.4] vs. 5.0 [95% CI = 4.5-5.6], respectively; P < 0.05}, with no difference observed in TMD patients. The depression and somatization scores were significantly higher in Group A than in Group B among BMS patients [0.57 (95% CI = 0.45-0.69) vs. 0.46 (95% CI = 0.34-0.59) and 0.537 (95% CI = 0.45-0.63) vs. 0.45 (95% CI = 0.34-0.55); P < 0.05], with no difference observed in TMD patients. The results of the present study indicate that pain intensities and psychosocial characteristics in BMS appear to differ between middle-aged and older patients.

Age-related associations between psychological characteristics and pain intensity among Japanese patients with temporomandibular disorder.

We investigated the relationship between pain intensity and psychosocial characteristics in patients with temporomandibular disorder (TMD). Participants with painful TMD, according to the Research Diagnostic Criteria for TMD (RDC/TMD), were recruited from our clinic and classified into six age groups: 15 to 24, 25 to 34, 35 to 44, 45 to 54, 55 to 64, and 65 to 85 years (Groups A through F, respectively). Self-reported present pain intensity and worst pain intensity during the past 6 months were ascertained using a numeric rating scale (0 to 10). Depression and somatization scores were evaluated using the RDC/TMD axis II questionnaire. Among women, worst pain intensity was significantly lower in Groups E and F than in Groups B and C (P < 0.05). In Groups A, C, and D, depression scores were significantly higher in women than in men (P < 0.05). Among women, depression score was significantly lower in Group F than in Groups A through C (P < 0.05). In Groups A through D, somatization scores were significantly higher for women than for men (P < 0.05). Depression score and TMD symptom severity appear to decrease with age in women.

Pain intensity and psychosocial characteristics of patients with burning mouth syndrome and trigeminal neuralgia.

This study compared pain intensity and psychosocial characteristics between patients with burning mouth syndrome (BMS) and those with trigeminal neuralgia (TN). Data from 282 patients with BMS and 83 patients with TN were analyzed. Patients reported duration of illness: duration ≤ 6 months was defined as acute illness and > 6 months as chronic illness. Present pain intensity and worst pain intensity during the past 6 months were reported using a 0-10 numeric rating scale (NRS). In addition, depression and somatization scores were evaluated on questionnaires. Patients with chronic BMS reported significantly higher pain intensity and had worse psychosocial characteristics than did those with acute BMS. Pain intensity was higher in TN patients than in BMS patients, although neither pain intensity nor psychosocial characteristics significantly differed between patients with acute and chronic illness. Logistic regression analysis of BMS and TN patients revealed that the odds ratio for worst pain was significantly lower for BMS patients than for TN patients and that the odds ratio for somatization score was 3.8 times higher in BMS patients. These findings suggest that BMS patients may require pain control targeting the central nervous system or psychosocial characteristics.

A novel method to isolate mesenchymal stem cells from bone marrow in a closed system using a device made by nonwoven fabric.

Bone marrow stromal cells (BMSCs) include cells with multidirectional differentiation potential described as mesenchymal stem cells. For clinical use, it is important to develop a way to isolate BMSCs from bone marrow in a closed system without centrifugation. After screening 200 biomaterials, we developed a device containing a nonwoven fabric filter composed of rayon and polyethylene. The filter selectively traps BMSCs among mononuclear cells in bone marrow based on affinity, not cell size. The cells are then recovered by the retrograde flow. Using canine and human bone marrow cells, the biological properties of BMSCs isolated by the device were compared with those obtained by conventional methods using centrifugation. The total number isolated by the device was larger, as was the number of CD106(+)/STRO-1(+) double-positive cells. The cells showed osteogenic, chondrogenic, and adipogenic differentiation potential in vitro. Finally, the direct transplantation of cells isolated by the device without in vitro cultivation accelerated bone regeneration in a canine model of osteonecrosis in vivo. The proposed method is rapid and efficient, does not require a biological clean area, and will be useful for the clinical application of mesenchymal stem cells in bone marrow.

Pancreatic expression and mitochondrial localization of the progestin-adipoQ receptor PAQR10.

Steroid hormones induce changes in gene expression by binding to intracellular receptors that then translocate to the nucleus. Steroids have also been shown to rapidly modify cell function by binding to surface membrane receptors. We identified a candidate steroid membrane receptor, the progestin and adipoQ receptor (PAQR) 10, a member of the PAQR family, in a screen for genes differentially expressed in mouse pancreatic beta-cells. PAQR10 gene expression was tissue restricted compared with other PAQRs. In the mouse embryonic pancreas, PAQR10 expression mirrored development of the endocrine lineage, with PAQR10 protein expression confined to endocrine islet-duct structures in the late embryo and neonate. In the adult mouse pancreas, PAQR10 was expressed exclusively in islet cells except for its reappearance in ducts of maternal islets during pregnancy. PAQR10 has a predicted molecular mass of 29 kDa, comprises seven transmembrane domains, and, like other PAQRs, is predicted to have an intracellular N-terminus and an extracellular C-terminus. In silico analysis indicated that three members of the PAQR family, PAQRs 9, 10, and 11, have a candidate mitochondrial localization signal (MLS) at the N-terminus. We showed that PAQR10 has a functional N-terminal MLS and that the native protein localizes to mitochondria. PAQR10 is structurally related to some bacterial hemolysins, pore-forming virulence factors that target mitochondria and regulate apoptosis. We propose that PAQR10 may act at the level of the mitochondrion to regulate pancreatic endocrine cell development/survival.

[Intraarterial concomitant chemoradiation for tongue cancer: analysis of 20 patients].

Subjects were 20 patients with tongue cancer treated between April 1996 and December 2002 with intraarterial infusion of cisplatin (60-120 mg/m2) (and docetaxel 10-30 mg/m2) and intravenous infusion of sodium thiosulfate followed by 5-fluorouracil (5-FU) (800-1000 mg/m2) for 3 to 5 days. All patients underwent radiation (50-80 Gy). Ten had stage II, 4 stage III, and 6 stage IV A disease. Complete response at the primary site was achieved in 50% for T2, 67% for T3, and 0% for T4 lesions in those undergoing IA cisplatin followed by systemic 5-FU with concurrent radiation. Complete response at the primary site was achieved in all patients given IA cisplatin and docetaxel followed by systemic 5-FU with concurrent radiation. Disease-specific survival was 75% and overall survival 69% at 5 years. Side effects of treatment were tolerable, except for grade three radiomucositis in 70% of patients and grade three bone marrow depression in one treated with weekly IA chemotherapy.

Harp (harmonin-interacting, ankyrin repeat-containing protein), a novel protein that interacts with harmonin in epithelial tissues.

Mutations in the triple PDZ domain-containing protein harmonin have been identified as the cause of Usher deafness syndrome type 1C. Independently, we identified harmonin in a screen for genes expressed in pancreatic beta cells. Using a yeast two-hybrid assay, we show that the first PDZ domain of harmonin interacts with a novel protein, designated harp for harmonin-interacting, ankyrin repeat-containing protein. This interaction was confirmed in an over-expression system and in mammalian cells, and shown to be mediated by the three C-terminal amino acids of harp. Harp is expressed in many of the same epithelia as harmonin and co-localization of native harp and harmonin was demonstrated by confocal microscopy in pancreatic duct epithelium and in a pancreatic beta-cell line. Harp, predicted molecular mass 48 kDa, has a domain structure which includes three ankyrin repeats and a sterile alpha motif. Human harp maps to chromosome 16, and its mouse homologue to chromosome 7. Sequences with similarity to harp include the sans gene, mutations of which are responsible for deafness in the Jackson shaker 2 (js) mutant mouse and in human Usher syndrome type 1G. The functional domain structures of harp and harmonin, their interaction under native conditions and their co-localization suggest they constitute a scaffolding complex to facilitate signal transduction in epithelia.

Antitumor effects of epidermal growth factor receptor antisense oligonucleotides in combination with docetaxel in squamous cell carcinoma of the head and neck.

PURPOSE: Antisense approaches targeting the epidermal growth factor receptor (EGFR) have been demonstrated to inhibit the growth of squamous cell carcinoma of the head and neck (SCCHN). Docetaxel is an effective chemotherapeutic agent in the treatment of SCCHN. The present study was undertaken to evaluate the antitumor mechanisms of EGFR antisense (AS) oligonucleotides administered in combination with docetaxel in preclinical models of SCCHN. EXPERIMENTAL DESIGN: SCCHN cells lines and xenografts were treated with an EGFR AS oligonucleotide targeting region 760-779 of EGFR mRNA (GenBank accession XM_004738) alone and in combination with docetaxel. Proliferation in vitro and tumor growth in vivo were examined in addition to determinations of EGFR expression and signaling pathways to evaluate antitumor mechanisms. RESULTS: A combination of docetaxel with EGFR AS resulted in increased cytotoxicity compared with treatment with docetaxel plus EGFR sense oligonucleotides or docetaxel alone after 24 h. Tumor volumes were significantly reduced in the mice treated with a combination of intratumoral EGFR AS and systemic docetaxel compared with mice receiving monotherapy. The combination of docetaxel plus EGFR AS resulted in decreased expression levels of EGFR, phosphotyrosine signal transducers and activators of transcription 3, vascular endothelial growth factor, and pAKT compared with expression levels after either treatment alone. CONCLUSIONS: A combination of EGFR AS and docetaxel may be effective in the treatment of SCCHN with a reduced toxicity profile compared with standard chemotherapy regimens.

STAT3 activation abrogates growth factor dependence and contributes to head and neck squamous cell carcinoma tumor growth in vivo.

Epidermal growth factor receptor (EGFR) is up-regulated and contributes to the loss of growth control in squamous cell carcinoma of the head and neck (SCCHN). Previously, we reported an association between autocrine stimulation of EGFR and constitutive signal transducers and activators of transcription (STAT) 3 activation in SCCHN cells in vitro and in vivo. Here, we evaluated the role of activated STAT3 in tumor progression and EGFR-independent mitogenic signaling. We found that SCCHN cells stably transfected with a dominant active STAT3 construct expressed elevated levels of STAT3 target genes, including Bcl-X(L) and cyclin D1, and demonstrated increased proliferation in vitro and more rapid tumor growth rates in vivo. Cell cycle analysis demonstrated an increased proportion of STAT3 construct transfectants in G(2)-M. These findings provide evidence that constitutive STAT3 activation contributes to tumor growth in SCCHN, independent of the EGFR autocrine axis.