Salvage surgery following tyrosine kinase inhibitor treatment for advanced non-small cell lung cancer.

BACKGROUND: No standard therapy for non-small lung cancer patients that have acquired resistance to tyrosine kinase inhibitor (TKI) therapy has been established. Some can be effectively treated by salvage surgery, though indications for that procedure remain unclear. Reported here is the clinical course of a patient who experienced early post-operative distant metastases. CASE PRESENTATION: A 48-year-old woman without symptoms was referred to another hospital for abnormal chest radiography findings and diagnosed with adenocarcinoma of the left lower lobe (cT2aN3M1b, stage IVB; TNM staging 7th edition). Gene mutation analysis revealed positive for epidermal growth factor receptor exon 19 deletion. Afatinib treatment was started, resulting in partial response, though regrowth of the main tumor was noted 1.5 years later. Bronchoscopic re-biopsy findings revealed a T790M point mutation and afatinib was switched to osimertinib. At 1.5 years following the start of osimertinib administration, the primary tumor was found to have regrown again and stereotactic radiation therapy was administered. Findings at 3.5 years after osimertinib administration indicated that all lymph nodes and distant metastases, excluding the primary tumor, were well controlled, and the patient was referred to our hospital for salvage surgery. Osimertinib was discontinued, and a left lower lobectomy with a left lingular segmentectomy and pleural biopsy were performed. The patient was discharged following an uneventful postoperative course. Three days after discharge, glossodynia developed and examination findings revealed tongue metastasis. The symptoms improved following re-administration of osimertinib, though right adrenal gland metastasis appeared 8 months after surgery. Radiation therapy was performed for tongue and right adrenal gland metastases, and the patient was alive 1 year after salvage surgery without out-of-control lesion appearing after the radiation therapy under the administration of osimertinib. CONCLUSION: The present patient experienced multiple instances of systemic recurrence after undergoing salvage surgery. Experience with this case indicates that systemic therapy is essential for patients with distant metastatic lung cancer even following salvage surgery for the primary tumor.

Native lung surgery after single lung transplantation: clinical characteristics and outcomes.

PURPOSE: Single lung transplantation (SLT) is a viable option for patients with end-stage pulmonary parenchymal and vascular diseases. However, various diseases can occur in native lungs after SLT. METHODS: Between January 2000 and December 2021, 35 patients underwent cadaveric SLT and survived for more than 30 days in our hospital. Among these 35 patients, 10 required surgery for diseases that developed in their native lungs. The clinical characteristics of these 10 patients and the outcomes of native lung surgery (NLS) were investigated. RESULTS: Among these ten patients, the indications for lung transplantation were chronic obstructive pulmonary disease and idiopathic interstitial pneumonia in three patients each, and lymphangioleiomyomatosis and collagen vascular disease-related interstitial pneumoniain two patients each. The causes of NLS included pneumothorax (n = 4), primary lung cancer (n = 2), native lung hyperinflation (n = 2), and pulmonary aspergilloma (n = 2). The surgical procedures were pneumonectomy (n = 7), lobectomy (n = 2), and alveolar-pleural fistula repair (n = 1). Only one postoperative complication, empyema, was treated with antibiotics. The 5-year overall survival rates after transplantation with and without NLS were 70.0% and 80.0%, respectively, and did not differ to a statistically extent (p = 0.56). CONCLUSION: NLS is an effective treatment option for diseases that develop in the native lungs after SLT.

Relationship of Higher-level Functional Capacity With Long-term Mortality in Japanese Older People: NIPPON DATA90.

BACKGROUND: Basic and instrumental activities of daily living (BADL and IADL, respectively) are known predictors of mortality. However, the relationship between higher-level functional capacity (HLFC) and mortality and related sex differences have rarely been investigated. METHODS: A prospective population-based cohort study was conducted in 1,824 older residents (≥65 years) with independent BADL from 300 randomly selected areas in Japan from 1995, and the participants were followed up until 2010. Using the Cox proportional hazards model, the relationship between HLFC and mortality risk was investigated, with adjustment for possible confounders. HLFC was assessed using the Tokyo Metropolitan Institute of Gerontology Index of Competence. Baseline data were collected using a questionnaire or by home-visit interviews. RESULTS: During an average 12.2-year follow-up, all-cause death was observed in 836 (45.8%) participants. Impaired HLFC was significantly associated with mortality (hazard ratio [HR] 1.37; 95% confidence interval [CI], 1.13-1.65). Lower social role was significantly associated with higher mortality risk in men (HR 1.38; 95% CI, 1.13-1.68). Lower IADL and intellectual activity were significantly associated with higher mortality risk in women (HR 1.50; 95% CI, 1.15-1.95 and HR 1.46; 95% CI, 1.19-1.79, respectively). The relationship between HLFC and mortality risk showed a similar tendency among cardiovascular diseases, stroke, cancer, and pneumonia. CONCLUSION: Impaired HLFC was associated with a high risk of all-cause mortality among community-dwelling older people with independent BADL. In particular, social role in men and IADL and intellectual activity in women were associated with long-term mortality risk.

G-CSF-producing left lung squamous cell carcinoma positive for ROS1 rearrangements completely resected after neoadjuvant radiation chemotherapy: A case report.

Granulocyte colony-stimulating factor (G-CSF) promotes neutrophil production. G-CSF-producing tumors have a feature of neutrophilia without infection, and most patients with G-CSF-producing tumors show an aggressive clinical course and poor prognosis. A 71-year-old woman was diagnosed with left lung cancer, cT4N1M0, stage IIIA. Severe neutrophilia and bone marrow uptake in 18-fluorodeoxyglucose-positron emission tomography suggested the possibility of G-CSF-producing lung cancer. Following neoadjuvant radiation chemotherapy, left lower lobectomy and left upper lobe partial resection were performed. According to pathology findings of the resected specimen, the patient was diagnosed with G-CSF-producing left lung squamous cell carcinoma. Moreover, genetic tests showed that the tumor cells were positive for c-ros oncogene 1 (ROS1) rearrangements. To our knowledge, this is the first reported case of G-CSF-producing lung cancer with ROS1 rearrangements, and complete resection was performed successfully after neoadjuvant radiation chemotherapy.

Two cases of lobectomy for lung cancer after transcatheter aortic valve implantation.

BACKGROUND: The age of patients with lung cancer is advancing, and the number of patients with lung cancer who have cardiac diseases is expected to increase. Recently, the rate of transcatheter aortic valve implantation (TAVI) has increased as treatment for aortic stenosis (AS). TAVI is minimally invasive compared with conventional aortic valve replacement. We herein report two patients with lung cancer who underwent lobectomy after TAVI for severe AS. CASE PRESENTATION: Two patients with AS and lung cancer were treated with two-stage surgery of TAVI followed by lobectomy. In patient 1 (77 years of age), conventional aortic valve replacement was considered to be risky because of his history of coronary artery disease and thoracic aortic aneurysm and his relatively high logistic euroSCORE. He underwent TAVI followed by right middle and lower lobectomy. In patient 2 (75 years of age), TAVI was chosen because the patient had poor ADL due to spinal canal stenosis and had taken immunosuppressant agents after a kidney transplantation. He underwent TAVI followed by right lower lobectomy. The postoperative course of the two patients was uneventful. CONCLUSIONS: Two-stage surgery of TAVI and lung resection could be a viable option for patients with both lung cancer and severe AS, for whom conventional AVR by an open-heart operation is not indicated.

[Indication of Palliative Gastrojejunostomy for Unresectable Advanced Gastric Cancer with Obstruction from the View Point of Preoperative Inflammatory Biomarkers].

Palliative surgery for advanced gastric cancer with serious symptoms such as hemorrhage or obstruction may be meaningful in the point of improving quality of life(QOL). However, the meaning of palliative gastrojejunostomy for unresectable gastric cancer with obstruction is controversial. We retrospectively evaluated the effectiveness of gastrojejunostomy for unresectable gastric cancer with obstruction using preoperative inflammatory biomarkers. Blood lymphocyte monocyte ratio(LMR), neu- trophill ymphocyte ratio(NLR)and C-reactive protein/albumin ratio(CAR)were analyzed as inflammatory biomarkers in this study. The percentage of improvement in food intake, discharge from the hospitaland performance of chemotherapy were significantly higher in the patients without any preoperative inflammatory reaction compared to those with any inflammation. Moreover, the survival of the patients without any inflammatory change was significantly longer compared to those with any inflammation. In conclusion, preoperative status of inflammation may be a useful marker to predict the effect and outcome of palliative gastrojejunostomy for unresectable gastric cancer with obstruction. Especially when there is any inflammation, the surgical indication should be carefully judged.

[Subtotal Esophagectomy for Mediastinal Lymph Node Oligo-Recurrence of ALK-Positive Lung Adenocarcinoma - A Case Report].

The patient was a 54-year-old woman with anaplastic lymphoma kinase-positive stage III B lung cancer. She received 4 courses of carboplatin(CBDCA)plus paclitaxel(PTX)plus bevacizumab(Bev)chemotherapy and crizotinib. Chemotherapy reduced the size of the primary site and mediastinal lymphadenopathy; however, the right supraclavicular and subcarinal lymph nodes were enlarged again during crizotinib treatment. Because it was an oligo-recurrence, we performed radiotherapy for these lymph nodes and changed systemic chemotherapy to alectinib. After 16 months, the patient exhibited esophageal stenosis due to subcarinal lymphadenopathy. We performed a subtotal esophagectomy, which improved the quality of life, and she was continued on an oral treatment of alectinib. Therefore, we suggest that an invasive surgical treatment is useful for oligo-recurrence cases.

[A Case of Surgical Treatment of Pulmonary Metastasis from Gastric Cancer].

An 87-year-old woman was diagnosed with advanced gastric cancer and primary lung cancer in November 2012. She underwent distal gastrectomy for the gastric cancer in December 2012, and right upper wedge resection for the primary lung cancer in February 2013. After surgery, the patient received S-1 chemotherapy. However, she subsequently experienced adverse effects, and so S-1 chemotherapy was stopped. In February 2016, a computed tomographic scan of the chest showed a nodular shadow at S8 in the left lung. Because the nodular shadow gradually increased in size, we suspected that the diagnosis would be either primary lung cancer or metastatic lung cancer arising from gastric cancer. In July 2016, we performed left lower wedge resection. Histopathological examination of the resected specimen resulted in a diagnosis of metastatic lung cancer arising from gastric cancer. After pulmonary resection, the patient had no recurrent tumor. It is thought that surgery is an effective treatment for solitary pulmonary metastasis arising from gastric cancer.

[Tracheal Resection and Primary Anastomosis for Adenoid Cystic Carcinoma Using an Extracorporeal Membrane Oxygenation].

We report a case of tracheal resection and primary anastomosis for adenoid cystic carcinoma using an extracorporeal membrane oxygenation (ECMO). A 45-year-old female was referred to our hospital because of a tracheal tumor that occupied most of the tracheal lumen. In case of airway obstruction by the tracheal tumor during anesthesia and operation, we decided to use ECMO before induction of general anesthesia. Under secure respiratory control using ECMO, tracheal resection and primary anastomosis was performed. Since histopathological examination revealed microscopically positive results at the surgical margin, postoperative adjuvant radiation therapy( 60 Gy/30 Fr) was conducted. Although a tracheal tumor is a relatively rare neoplasm, careful planning and a treatment strategy are necessary with special emphasis on the location and size of tumor. In this case, ECMO made a substantial contribution to secure respiratory control during surgery.

The management of secondary frozen shoulder after anterior shoulder dislocation - The results of manipulation under anaesthesia and injection.

INTRODUCTION: Patients with secondary frozen shoulder following anterior dislocation were treated with manipulation under anaesthesia (MUA) and injection. METHODS: Ten patients included in study. Oxford Shoulder Scores (OSS), range of motion (ROM) and need for any further treatment measured. RESULTS: Mean follow-up of 93 weeks. OSS and ROM improved in all patients. Three patients required repeat MUA. Two patients developed recurrent instability. DISCUSSION: Secondary frozen shoulder may be more recalcitrant. Recurrent instability is a risk following anterior shoulder dislocation. It is feasible that by performing an MUA to maximise mobility, stability may be sacrificed. It should be performed with caution.

[A Case of Successful Treatment of Liver Metastases from Gastric Cancer with Chemotherapy].

A 69-year-old man was diagnosed with advanced gastric cancer accompanied by multiple liver metastases in April 2009. Because of worsening anemia due to bleeding from the primary tumor, we performed a distal gastrectomy. After gastrecto- my, he underwent S-1/CDDP combination chemotherapy. After 5 courses of chemotherapy, the size of the liver metastases was reduced. S-1/irinotecan combination chemotherapy was administered as second-line chemotherapy, but he developed grade 3 diarrhea, and the S-1/irinotecan combination chemotherapy was immediately stopped.Weekly paclitaxel chemother- apy was administered as third-line chemotherapy, and S-1/docetaxel combination chemotherapy was administered as fourth-line chemotherapy. After 11 courses of S-1/docetaxel combination chemotherapy, the liver metastases could not be detected by CT and PET-CT in October 2012, and it was concluded that a complete response(CR)had been obtained. He receive maintenance therapy with S-1 chemotherapy for 10 months. Now, he is alive without chemotherapy and has maintained a CR for 4 years 8 months after achieving a CR.

Antibacterial Activity of Curcumin Against Periodontopathic Bacteria.

BACKGROUND: Curcumin is a polyphenol extracted from root of turmeric and known to possess multifunctional properties, including antibacterial activity. Although previous studies have investigated the effects of curcumin on microorganisms, available knowledge on the effects of curcumin on periodontopathic bacteria is still limited. In this study, the antibacterial effect of curcumin on periodontopathic bacteria is investigated, particularly Porphyromonas gingivalis. METHODS: Representative periodontopathic bacteria were cultured in media with and without various curcumin concentrations, and the optical density at 600 nm was measured for 60 hours. The inhibitory effect of curcumin on P. gingivalis Arg- and Lys-specific proteinase (RGP and KGP, respectively) activities were assessed using spectrofluorophotometric assay. Analysis of biofilm formation by P. gingivalis with or without Streptococcus gordonii was conducted using confocal laser-scanning microscopy (CLSM). RESULTS: Curcumin inhibited the growth of P. gingivalis, Prevotella intermedia, Fusobacterium nucleatum, and Treponema denticola in a dose-dependent manner. Bacterial growth was suppressed almost completely at very low concentrations of curcumin. Conversely, 100 µg/mL curcumin did not suppress the growth of Aggregatibacter actinomycetemcomitans. It also demonstrated inhibitory effects against RGP and KGP activities in a dose-dependent manner. CLSM revealed that curcumin suppressed P. gingivalis homotypic and P. gingivalis-S. gordonii heterotypic biofilm formation in a dose-dependent manner. A concentration of 20 µg/mL curcumin inhibited these P. gingivalis biofilm formations by >80%. CONCLUSION: Curcumin possesses antibacterial activity against periodontopathic bacteria and may be a potent agent for preventing periodontal diseases.

Proteomic and transcriptional analysis of interaction between oral microbiota Porphyromonas gingivalis and Streptococcus oralis.

Porphyromonas gingivalis, a major periodontal pathogen, forms biofilm with other oral bacteria such as streptococci. Here, by using shotgun proteomics, we examined the molecular basis of mixed-biofilm formation by P. gingivalis with Streptococcus oralis. We identified a total of 593 bacterial proteins in the biofilm. Compared to the expression profile in the P. gingivalis monobiofilm, the expression of three proteins was induced and that of 31 proteins was suppressed in the mixed biofilm. Additionally, the expression of two S. oralis proteins was increased, while that of two proteins was decreased in the mixed biofilm, as compared to its monotypic profile. mRNA expression analysis of selected genes using a quantitative reverse transcription polymerase chain reaction confirmed the proteomics data, which included overexpression of P. gingivalis FimA and S. oralis glyceraldehyde-3-phosphate dehydrogenase in association with the biofilm. The results also indicated that S. oralis regulates the transcriptional activity of P. gingivalis luxS to influence autoinducer-2-dependent signaling. These findings suggest that several functional molecules are involved in biofilm formation between P. gingivalis and S. oralis.

Identification and characterization of Porphyromonas gingivalis client proteins that bind to Streptococcus oralis glyceraldehyde-3-phosphate dehydrogenase.

Coaggregation of Porphyromonas gingivalis and oral streptococci is thought to play an important role in P. gingivalis colonization. Previously, we reported that P. gingivalis major fimbriae interacted with Streptococcus oralis glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and that amino acid residues 166 to 183 of GAPDH exhibited strong binding activity toward P. gingivalis fimbriae (H. Nagata, M. Iwasaki, K. Maeda, M. Kuboniwa, E. Hashino, M. Toe, N. Minamino, H. Kuwahara, and S. Shizukuishi, Infect. Immun. 77:5130-5138, 2009). The present study aimed to identify and characterize P. gingivalis components other than fimbriae that interact with S. oralis GAPDH. A pulldown assay was performed to detect potential interactions between P. gingivalis client proteins and S. oralis recombinant GAPDH with amino acid residues 166 to 183 deleted by site-directed mutagenesis. Seven proteins, namely, tonB-dependent receptor protein (RagA4), arginine-specific proteinase B, 4-hydroxybutyryl-coenzyme A dehydratase (AbfD), lysine-specific proteinase, GAPDH, NAD-dependent glutamate dehydrogenase (GDH), and malate dehydrogenase (MDH), were identified by two-dimensional gel electrophoresis followed by proteomic analysis using tandem mass spectrometry. Interactions between these client proteins and S. oralis GAPDH were analyzed with a biomolecular interaction analysis system. S. oralis GAPDH showed high affinity for five of the seven client proteins (RagA4, AbfD, GAPDH, GDH, and MDH). Interactions between P. gingivalis and S. oralis were measured by a turbidimetric method and fluorescence microscopy. RagA4, AbfD, and GDH enhanced coaggregation, whereas GAPDH and MDH inhibited coaggregation. Furthermore, the expression of luxS in P. gingivalis was upregulated by RagA4, AbfD, and GDH but was downregulated by MDH. These results indicate that the five P. gingivalis client proteins function as regulators in P. gingivalis biofilm formation with oral streptococci.

Effect of eucalyptus-extract chewing gum on oral malodor: a double-masked, randomized trial.

BACKGROUND: Eucalyptus extracts were found to possess an antibacterial activity against some oral pathogens that produce oral malodor compounds in vitro; however, the clinical effects with respect to oral malodor in humans remain unproven. In the present investigation, a randomized clinical study was designed to test the hypothesis that eucalyptus-extract chewing gum can reduce oral malodor in the general adult population. METHODS: Subjects were randomly assigned to the following three groups: a high-concentration (0.6% eucalyptus extract) group (n = 32), a low-concentration (0.4% eucalyptus extract) group (n = 32), and a placebo group (n = 33). The intake period was 12 weeks. The organoleptic score, level of volatile sulfur compounds (VSCs), and tongue-coating score were recorded at baseline and 4, 8, 12, and 14 weeks. Treatment-to-time interactions among groups were evaluated by repeated-measures analysis of variance (ANOVA) followed by the Games-Howell pairwise comparison test. RESULTS: Relative to baseline readings, significant reductions in clinical parameters, including organoleptic and tongue-coating scores in the high- and/or low-concentration groups, occurred at 4, 8, 12, and 14 weeks (P <0.05). In addition, group-time interactions revealed significant reductions in the organoleptic score, VSCs, and tongue-coating score in both concentration groups compared to the placebo group (P <0.05). CONCLUSIONS: Eucalyptus-extract chewing gum had long-term effects on the olganoleptic score, levels of VSCs, and tongue-coating score. These findings suggest that eucalyptus-extract chewing gum may reduce oral malodor by decreasing the accumulation of tongue coating.

Identification of the binding domain of Streptococcus oralis glyceraldehyde-3-phosphate dehydrogenase for Porphyromonas gingivalis major fimbriae.

Porphyromonas gingivalis forms communities with antecedent oral biofilm constituent streptococci. P. gingivalis major fimbriae bind to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) present on the streptococcal surface, and this interaction plays an important role in P. gingivalis colonization. This study identified the binding domain of Streptococcus oralis GAPDH for P. gingivalis fimbriae. S. oralis recombinant GAPDH (rGAPDH) was digested with lysyl endopeptidase. Cleaved fragments of rGAPDH were applied to a reverse-phase high-pressure liquid chromatograph equipped with a C18 column. Each peak was collected; the binding activity toward P. gingivalis recombinant fimbrillin (rFimA) was analyzed with a biomolecular interaction analysis system. The fragment displaying the strongest binding activity was further digested with various proteinases, after which the binding activity of each fragment was measured. The amino acid sequence of each fragment was determined by direct sequencing, mass spectrometric analysis, and amino acid analysis. Amino acid residues 166 to 183 of S. oralis GAPDH exhibited the strongest binding activity toward rFimA; confocal laser scanning microscopy revealed that the synthetic peptide corresponding to amino acid residues 166 to 183 of S. oralis GAPDH (pep166-183, DNFGVVEGLMTTIHAYTG) inhibits S. oralis-P. gingivalis biofilm formation in a dose-dependent manner. Moreover, pep166-183 inhibited interbacterial biofilm formation by several oral streptococci and P. gingivalis strains with different types of FimA. These results indicate that the binding domain of S. oralis GAPDH for P. gingivalis fimbriae exists within the region encompassing amino acid residues 166 to 183 of GAPDH and that pep166-183 may be a potent inhibitor of P. gingivalis colonization in the oral cavity.

Effect of eucalyptus extract chewing gum on periodontal health: a double-masked, randomized trial.

BACKGROUND: Studies in vitro showed that eucalyptus extracts possess antibacterial activity against cariogenic and periodontopathic bacteria; however, the clinical effects with respect to periodontal health in humans remain unproven. The objective of this study was to evaluate the effect of chewing gum containing eucalyptus extract on periodontal health in a double-masked, randomized, controlled trial. METHODS: Healthy humans with gingivitis but not deep periodontal pockets were randomly assigned to the following groups: high-concentration group (n=32): use of 0.6% eucalyptus extract chewing gum for 12 weeks (90 mg/day); low-concentration group (n=32): use of 0.4% eucalyptus extract chewing gum for 12 weeks (60 mg/day); and placebo group (n=33): use of chewing gum without eucalyptus extract for 12 weeks. Plaque accumulation (PLA), gingival index (GI), bleeding on probing (BOP), periodontal probing depth (PD), and clinical attachment level (CAL) were measured at weeks 0, 4, 8, 12, and 14. Significance was analyzed with repeated-measures two-way analysis of variance followed by the Games-Howell pairwise comparison test. RESULTS: The interaction between the effects of eucalyptus extract chewing gum and the intake period was statistically significant for PLA, GI, BOP, and PD but not for CAL. The low- and high-concentration groups exhibited statistically significant (P <0.05) improvements compared to the placebo group for PLA, GI, BOP, and PD. CONCLUSIONS: Eucalyptus extract chewing gum had a significant effect on PLA, GI, BOP, and PD. The use of eucalyptus extract chewing gum may promote periodontal health.

Involvement of minor components associated with the FimA fimbriae of Porphyromonas gingivalis in adhesive functions.

The FimA fimbriae of Porphyromonas gingivalis, the causative agent of periodontitis, have been implicated in various aspects of pathogenicity, such as colonization, adhesion and aggregation. In this study, the four open reading frames (ORF1, ORF2, ORF3 and ORF4) downstream of the fimbrilin gene (fimA) in strain ATCC 33277 were examined. ORF2, ORF3 and ORF4 were demonstrated to encode minor components of the fimbriae and were therefore renamed fimC, fimD and fimE, respectively. Immunoblotting analyses revealed that inactivation of either fimC or fimD by an ermF-ermAM insertion, but not inactivation of ORF1, was accompanied by concomitant loss of the products from the downstream genes, raising the possibility that fimC, fimD and fimE constitute a transcription unit. The fimE mutant produced FimC and FimD, but fimbriae purified from it contained neither protein, suggesting that FimE is required for the assembly of FimC and FimD onto the fimbrilin (FimA) fibre. The fimC, fimD and fimE mutants lost autoaggregation abilities. Fimbriae purified from these three mutants showed attenuated binding activities to glyceraldehyde-3-phosphate dehydrogenase of Streptococcus oralis and to two extracellular matrix proteins, fibronectin and type I collagen. These results suggest that FimE, as well as FimC and FimD, play critical roles in the adhesive activities of the mature FimA fimbriae in P. gingivalis.

Longitudinal study of the association between smoking as a periodontitis risk and salivary biomarkers related to periodontitis.

BACKGROUND: Insufficient data exist regarding the long-term influence of lifestyle factors including smoking on periodontal health. The objective of this study was to examine the prospective association between smoking and periodontal disease progression and the effects of smoking on salivary biomarkers related to periodontitis. METHODS: Probing depth (PD) was measured at health checkups of workers in 1999 and 2003; additionally, lifestyle information was obtained through a questionnaire. In 2003, 219 of 256 (86%) workers examined at baseline completed PD measurements; saliva samples were also collected. Change in PD was used for assessment of periodontitis progression when three or more sites displayed an increase of >or=2 mm over 4 years. Salivary biomarker levels were determined by real-time polymerase chain reaction and enzyme assay. Statistical methods included bivariate and multivariate regression analyses. RESULTS: In the multiple logistic model, in which lifestyle-related factors served as independent variables, significant variables were current smoking and hours of sleep; respective odds ratios were 2.3 and 2.1. Additionally, 38.5% of periodontal disease progression was attributable to current smoking. Moreover, pack-years of smoking showed a dose-response relationship with disease progression. Levels of salivary markers including prostaglandin E(2), lactoferrin, albumin, aspartate aminotransferase, lactate dehydrogenase, and alkaline phosphatase were significantly lower in current smokers than in non-current smokers. However, no meaningful differences in the proportions of six periodontal pathogens were observed between current and non-current smokers. CONCLUSIONS: Smoking exerted the greatest influence on periodontitis risk among lifestyle factors. Smoking may suppress the host-defense system, which may promote periodontal disease progression.

Nasal cholera toxin elicits IL-5 and IL-5 receptor alpha-chain expressing B-1a B cells for innate mucosal IgA antibody responses.

In this study, we examine whether native cholera toxin (nCT) as a mucosal adjuvant can support trinitrophenyl (TNP)-LPS-specific mucosal immune responses. C57BL/6 mice were given nasal TNP-LPS in the presence or absence of nCT. Five days later, significantly higher levels of TNP-specific mucosal IgA Ab responses were induced in the nasal washes, saliva, and plasma of mice given nCT plus TNP-LPS than in those given TNP-LPS alone. High numbers of TNP-specific IgA Ab-forming cells were also detected in mucosal tissues such as the nasal passages (NPs), the submandibular glands (SMGs), and nasopharyngeal-associated lymphoreticular tissue of mice given nCT. Flow cytometric analysis showed that higher numbers of surface IgA+, CD5+ B cells (B-1a B cells) in SMGs and NPs of mice given nasal TNP-LPS plus nCT than in those given TNP-LPS alone. Furthermore, increased levels of IL-5R alpha-chain were expressed by B-1a B cells in SMGs and NPs of mice given nasal TNP-LPS plus nCT. Thus, CD4+ T cells from these mucosal effector lymphoid tissues produce high levels of IL-5 at both protein and mRNA levels. When mice were treated with anti-IL-5 mAb, significant reductions in TNP-specific mucosal IgA Ab responses were noted in external secretions. These findings show that nasal nCT as an adjuvant enhances mucosal immune responses to a T cell-independent Ag due to the cross-talk between IL-5Ralpha+ B-1a B cells and IL-5-producing CD4+ T cells in the mucosal effector lymphoid tissues.