Prevalence of early and late oral implant loss among smokers: a nationwide survey in Japan.

A cross-sectional, nationwide survey was conducted in Japan to examine the relationship between tobacco smoking and oral diseases including implant failure. A questionnaire survey was sent to designated facilities by post, and 158 answered questions regarding implant loss. Smoking status, number of implant failures, and other related variables were collected from the participating dentists as secondary data. A total of 1966 patients who were treated with dental implants by participating dentists during the survey period were analysed. Among the total sample, 90 (5%) had early implant loss (≤12 months) and 153 (8%) had late implant loss (>12 months and ≤120 months). The number of pack-years was significantly higher in the total (early and late) implant loss group (31.2±15.9) than in the group with no implant loss (26.1±18.1) (P=0.026). In the multivariate analysis, the number of implants installed, smoking, and pack-years were significant factors for total implant loss. The adjusted odds ratio for implant failure for current smokers compared with never smokers was 2.07 (95% CI 1.19-3.62) for early implant loss and 1.48 (95% CI 0.92-2.37) for late implant loss. This study reaffirms that current smoking is associated with an increased risk of early implant loss, irrespective of the duration of smoking exposure.

Recurrent Spindle Cell Carcinoma Shows Features of Mesenchymal Stem Cells.

This study investigated a case of spindle cell carcinoma (SpCC) in tongue pathological lesions. The patient experienced a local recurrence and distant metastasis after surgical intervention. Although standard chemotherapy was administered, a granulomatous mass continued to develop. This aggressive growth led to survival of the tumor. Secondary debulking surgery was performed to improve the patient's quality of life at the request of the patient. Using a tissue sample derived from the secondary debulking surgery, we performed an analysis of the tumor's cell surface antigens, differentiation potential, metastatic ability, and inhibition potential by anticancer reagents. In vitro analysis revealed that the cell population grown under adherent culture conditions expressed the mesenchymal stem cell (MSC) markers CD73, CD90, and CD105. The cell line established from this SpCC contained colony-forming unit fibroblasts (CFU-Fs) and exhibited multipotent differentiation into several mesenchymal lineages, including bone, cartilage, and fat. The SpCC cells also displayed vigorous mobilization. These characteristics suggested that they had the differentiation potential of mesenchymal cells, especially MSCs, rather than that of epithelial cells. The surgical specimen analyzed in this study resisted the molecular target reagent cetuximab, which is an epidermal growth factor receptor inhibitor. This clinical insight revealed that chemotherapy-resistant SpCC cells have different characteristics compared to most other cancer cells, which are sensitive to cetuximab. Our cell death assay revealed that SpCC cell death was induced by the anticancer drug imatinib, which is known to inhibit protein tyrosine kinase activity of ABL, platelet-derived growth factor receptor α (PDGFRα), and KIT. Here, we report recurrent SpCC with characteristics of MSCs and potential for treatment with imatinib.

Purified Human Dental Pulp Stem Cells Promote Osteogenic Regeneration.

Human dental pulp stem/progenitor cells (hDPSCs) are attractive candidates for regenerative therapy because they can be easily expanded to generate colony-forming unit-fibroblasts (CFU-Fs) on plastic and the large cell numbers required for transplantation. However, isolation based on adherence to plastic inevitably changes the surface marker expression and biological properties of the cells. Consequently, little is currently known about the original phenotypes of tissue precursor cells that give rise to plastic-adherent CFU-Fs. To better understand the in vivo functions and translational therapeutic potential of hDPSCs and other stem cells, selective cell markers must be identified in the progenitor cells. Here, we identified a dental pulp tissue-specific cell population based on the expression profiles of 2 cell-surface markers LNGFR (CD271) and THY-1 (CD90). Prospectively isolated, dental pulp-derived LNGFR(Low+)THY-1(High+) cells represent a highly enriched population of clonogenic cells--notably, the isolated cells exhibited long-term proliferation and multilineage differentiation potential in vitro. The cells also expressed known mesenchymal cell markers and promoted new bone formation to heal critical-size calvarial defects in vivo. These findings suggest that LNGFR(Low+)THY-1(High+) dental pulp-derived cells provide an excellent source of material for bone regenerative strategies.

Clinical utility of three-dimensional SPECT/CT imaging as a guide for the resection of medication-related osteonecrosis of the jaw.

In recent years, proactive surgical treatment has been reported to be effective for medication-related osteonecrosis of the jaw (MRONJ). However, an uncertain resection entails the risk of recurrence, whereas an extensive surgical procedure may lead to a marked reduction in quality of life as a result of reduced masticatory function and poor cosmesis. Therefore, radiological assessment can be helpful to accurately localize MRONJ before surgery. The integrated single-photon emission computed tomography and computed tomography system (SPECT/CT) allows oral and maxillofacial surgeons to identify an area of MRONJ, especially when three-dimensional (3D) SPECT and CT fusion images are offered. A patient for whom 3D SPECT and CT image fusion (as developed in the radiology department of the study institution) contributed to determining the extent of the lesion, thereby leading to a favourable patient prognosis, is reported herein. There was exact correlation between the histological and radiological results.

Age-associated changes in bovine oocytes and granulosa cell complexes collected from early antral follicles.

PURPOSE: To assess the age-associated changes in oocytes and granulosa cells derived from early antral follicles (EAFs). METHOD: Gene expression analysis of granulosa cells of the EAFs using a genome analyzer (Illumina) and in vitro culture of oocyte-granulosa cell complexes (OGCs) of EAFs (400-700 µm in diameter) collected from ovaries of aged (>120 months) and young (<50 months) cows. RESULTS: Gene expression profiles in granulosa cells of EAFs of aged cows, which included changes in genes that encode chaperone proteins and antioxidants. In vivo development of EAFs, as determined by oocyte diameter of EAFs and AFs (3-6 mm in diameter), appeared to be impaired in aged cows and the OGCs of aged cows contained low GSH compared to younger counterparts. When the OGCs were cultured in a medium containing low estradiol (E2, 0.1 µg/mL), the ratio of antrum formation was higher for OGCs from aged animals than that from young animals, while higher abnormal fertilization rate and lower total cell number of the blastocysts were observed in the OGCs of aged cows compared with those of young cows. On the contrary, when the OGCs were cultured in a medium containing 10 µg/mL E2, the ratio of antrum formation and fertilization outcome was comparable between the two age groups, whereas the total cell number of the blastocysts was still low in the aged group. CONCLUSION: Aging affects the gene expression profiles of the granulosa cells, and impairs in vitro developmental ability of OGCs collected from EAFs.

TNFα promotes osteosarcoma progression by maintaining tumor cells in an undifferentiated state.

Chronic inflammation is frequently associated with tumorigenesis in elderly people. By contrast, young people without chronic inflammation often develop tumors considered independent of chronic inflammation but driven instead by mutations. Thus, whether inflammation has a significant role in tumor progression in tumors driven by mutations remains largely unknown. Here we show that TNFα is required for the tumorigenesis of osteosarcoma, the most common tumor in children and adolescents. We show that transplantation of AX osteosarcoma cells, which harbor mutations driving c-Myc overexpression and Ink4a-deficiency, in wild-type mice promotes lethal tumorigenesis accompanied by ectopic bone formation and multiple metastases, phenotypes seen in osteosarcoma patients. Such tumorigenesis was completely abrogated in TNFα-deficient mice. AX cells have the capacity to undergo osteoblastic differentiation; however, that activity was significantly inhibited by TNFα treatment, suggesting that TNFα maintains AX cells in an undifferentiated state. TNFα inhibition of AX cell osteoblastic differentiation occurred through ERK activation, and a pharmacological TNFα inhibitor effectively inhibited both AX cell tumorigenesis and increased osteoblastic gene expression and increased survival of tumor-bearing mice. Lethal tumorigenesis of AX cells was also abrogated in IL-1α/IL-1ß doubly deficient mice. We found that both TNFα and IL-1 maintained AX cells in an undifferentiated state via ERK activation. Thus, inflammatory cytokines are required to promote tumorigenesis even in mutation-induced tumors, and TNFα/IL-1 and ERK may represent therapeutic targets for osteosarcoma.

Improvement of cardio-ankle vascular index by glimepiride in type 2 diabetic patients.

AIMS: Glimepiride, a third generation sulfonylurea (SU), is known to have extrapancreatic effects, but its vascular effect is unclear. We investigated the efficacy of glimepiride in improving arterial stiffness assessed by cardio-ankle vascular index (CAVI) in type 2 diabetic patients, compared with glibenclamide, a conventional SU. METHODS: Forty type 2 diabetic patients were randomly assigned to two groups. One group was administered glimepiride 1.5 mg/day, and the other group was administered glibenclamide 1.25 mg/day for 6 months. RESULTS: No significant difference in hypoglycaemic effect was observed between two groups. CAVI significantly decreased only in glimepiride group (9.4 ± 1.4→8.9 ± 0.8, p < 0.05). Decrease in CAVI was greater in glimepiride group than in glibenclamide group (-0.50 ± 0.98 vs. -0.04 ± 0.57, p = 0.048). Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) decreased in glimepiride group and increased in glibenclamide group, and the changes were significantly different between groups (-1.5 ± 3.5 vs. + 1.8 ± 3.6, p = 0.009); whereas serum lipoprotein lipase mass increased in glibenclamide group and decreased in glibenclamide group, and the changes tended to be different between groups (+ 2.1 ± 19.1 vs. -7.4 ± 19.2, p = 0.096). Change in urinary 8-OHdG was a significant independent predictor for change in CAVI in all subjects. CONCLUSIONS: These results suggest that glimepiride improves CAVI compared with glibenclamide. Reduced oxidative stress and improved insulin resistance may contribute to the improvement of CAVI by glimerpiride.

Efficiency of adenovirus-mediated gene transduction in heart grafts in rats.

AIM: We determined the characteristics of transgene expression of heart grafts following ex vivo gene transfer using an adenovirus vector. Transgene expression was assessed periodically in the same animals by a non-invasive bioimaging system. METHODS: Rat heterotopic heart transplantation was performed in a syngenic combination. We infused 1 x 10(9) plaque-forming units of adenovirus vectors containing firefly luciferase gene into the heart graft via the coronary artery, with preservation at 4 degrees C and transplanted into the cervix of the recipient. Transgene expression was periodically visualized and quantified by a noninvasive bioimaging system without sacrificing experimental animals. RESULTS: Transgene expression in the graft peaked at day 7 and then fell gradually. Transgene expression was also observed in the recipient liver. CONCLUSIONS: We have determined the time course of transgene expression in the heart graft. This constitutes important information about ex vivo gene therapy for heart grafts.

Effect of levofloxacin on theophylline clearance during theophylline and clarithromycin combination therapy.

OBJECTIVE: To report a case of decreased theophylline clearance by the addition of levofloxacin in a patient receiving theophylline and clarithromycin. CASE SUMMARY: A 59-year-old Japanese man who was receiving theophylline for emphysema experienced stimulation, insomnia, and tachycardia due to theophylline toxicity after clarithromycin and levofloxacin were added to the regimen. The combination of these agents resulted in a decrease in theophylline clearance to approximately 60% of the initial value obtained while the patient was receiving theophylline alone. The adverse effects disappeared after the dosage was reduced and the theophylline serum concentration decreased; however, there was no change in theophylline clearance. After discontinuation of levofloxacin, the theophylline serum concentration decreased, and theophylline clearance returned to the initial level even though clarithromycin was continued. DISCUSSION: Levofloxacin is believed not to influence the clearance of theophylline, although some new fluoroquinolones have been reported to do so. This case indicates that levofloxacin and clarithromycin inhibited theophylline metabolic pathways catalyzed by both CYP1A2 and CYP3A4 and resulted in the decrease in theophylline clearance. The clearance of theophylline, therefore, is not influenced by clarithromycin alone. CONCLUSIONS: Careful monitoring is required when levofloxacin is prescribed for patients who are taking clarithromycin with theophylline.

[Obesity and life style of Japanese school children with Down syndrome].

A questionnaire-based investigation was performed on 325 Japanese school children with Down syndrome ages 6 to 18. Data on height and body weight, eating habits, physical activity for these children were obtained through their parents. Proportion of obese children was higher among these subjects than the average for Japanese children (34.3% and 7.47% respectively, for the ages from 6 to 14). We examined characteristics of eating habits and physical activities between the obese group (obesity index greater than 20% above the average of Japanese school children) and the non-obese group. Obesity started to increase in the obese group around age 7. The obese group tended to have had a greater intake of sweets, juice and total foods in their preschool days, but unexpectedly had been physically more active in their primary school days.

Expression of cell cycle regulating proteins in an unusual transformation of mantle cell lymphoma.

We describe here two patients with mantle cell lymphoma (MCL) who after a few years, developed to the diffuse large cell lymphoma (DLCL) (anaplastic centrocytic lymphoma) growing in a diffuse sheets without the classical MCL component. In both the initial and second biopsy specimens, in each case, tumor cells were positive for cyclin D1, sIgM, sIgD, and CD5, but were negative for CD10 and CD23. In a study of immunoglobulin heavy chain (IgH) gene rearrangement, using the polymerase chain reaction (PCR) method, the products obtained from each paired biopsy tissue sample were the same size, and in one case had an identical sequence to the non-mutated VH gene. Immunohistochemistry was used to examine the expression of p53, p27Kip1 and cyclin E. Interestingly, there was clear overexpression of p53 protein in case 1 but not in case 2, compared with other typical MCL cases. The expression of p27Kip1 in the second biopsies of each case was decreased compared with those in the initial biopsies. In case 2, however, p27Kip1 was clearly expressed in the first and second biopsies, in contrast to other typical MCL cases. Thus these 2 cases demonstrate not only that the variant form of MCL may arise de novo, but also that MCL may transform to DLCL at the time of relapse. Although the mechanism of tumor progression/transformation is still poorly understood, the overexpression of p53 or p27Kip1 may be linked to a cellular mechanism involved in the development of the variant form of MCL.

Expression of Cell Cycle Regulating Proteins in an Unusual Transformation of Mantle Cell Lymphoma.

We describe here two patients with mantle cell lymphoma (MCL) who after a few years, developed to the diffuse large cell lymphoma (DLCL)( anaplastic centrocytic lymphoma) growing in a diffuse sheets without the classical MCL component. In both the initial and second biopsy specimens, in each case, tumor cells were positive for cyclin D1, sIgM, sIgD, and CD5, but were negative for CD10 and CD23. In a study of immunoglobulin heavy chain (IgH) gene rearrangement, using the polymerase chain reaction (PCR) method, the products obtained from each paired biopsy tissue sample were the same size, and in one case had an identical sequence to the non-mutated VH gene. Immunohistochemistry was used to examine the expression of p53, p27(Kip1) and cyclin E. Interestingly, there was clear overexpression of p53 protein in case 1 but not in case 2, compared with other typical MCL cases. The expression of p27(Kip1) in the second biopsies of each case was decreased compared with those in the initial biopsies. In case 2, however, p27(Kip1) was clearly expressed in the first and second biopsies, in contrast to other typical MCL cases. Thus these 2 cases demonstrate not only that the variant form of MCL may arise de novo, but also that MCL may transform to DLCL at the time of relapse. Although the mechanism of tumor progression/transformation is still poorly understood, the overexpression of p53 or p27(Kip1) may be linked to a cellular mechanism involved in the development of the variant form of MCL.

Role of p27Kip1 and cyclin-dependent kinase 2 in the proliferation of non-small cell lung cancer.

The cell cycle is governed by a family of cyclin-dependent kinases (Cdks). Cdk2 forms a functional complex with cyclin E and plays a pivotal role in the regulation of G1/S transition. Cdk2 activity is negatively regulated by interactions with inhibitors. p27Kip1, one of the most potent inhibitors of Cdk2, was recently identified as a powerful negative prognostic marker in non-small cell lung cancer as well as in colorectal and breast cancer. In the present study, the expression of p27 and Ki-67 antigen in nonneoplastic and cancerous lung tissues was determined by immunohistochemistry. After establishing that the antibody-measured p27 labeling index was a good reflection of the level of p27 expression measured by Western blotting, we show that p27 labeling index is decreased in cancerous lung tissues, compared with nonneoplastic lung tissues, and exhibits a significant inverse relation to the proliferation marker Ki-67 antigen, detected with monoclonal antibody MIB-1. Consistent with these data, all cancerous lung tissues showed enhanced degradation activity of p27 compared with nonneoplastic lung tissues and, in addition, increased levels of the phosphorylated form of Cdk2, as determined with Western blot analysis. The H1 histone kinase activity associated with Cdk2 was also increased in non-small cell lung cancers. Statistical analysis showed that proliferative activity as measured by MIB-1 labeling index was highly correlated with Cdk2 activity (r = 0.767, P < 0.0015). These results suggest that p27 and Cdk2 may play an important role in the proliferation of non-small cell cancer.

[A case report of left postero-lateral thoracotomy for simultaneous CABG and left lower lobectomy].

Surgical management of patients with concomitant resectable lung lesions and critical cardiac disease is controversial. We report a case of concomitant pulmonary and cardiac surgery via a left thoracotomy. A 67-year-old male was admitted to our hospital complaining of recurrent bloody sputum and an abnormal shadow on chest X-ray. Chest CT and MRI showed a tumor in the left lower lobe (S10), with invasion of the diaphragm. A diagnosis of squamous cell carcinoma was obtained by transbronchial lung biopsy. The patient had a history of angina pectoris, and stress testing was positive. Coronary angiography showed 90% stenosis at segment 5, suggesting a risk of perioperative or postoperative myocardial infarction. This necessitated simultaneous surgical treatment for lung cancer and ischemic heart disease. A lobectomy of the left lower lung was performed, followed by coronary artery bypass grafting (CABG), using the great saphenous vein. The postoperative course was uneventful except for the occurrence of cholecystitis. Lung cancer and ischemic heart disease can be safely treated simultaneously via a single incision, with and benefit for selected patients.

[Exercise tolerance assessed by unilateral pulmonary artery occlusion test before and after pulmonary resection].

Pre- and post-operative exercise tests and unilateral pulmonary artery occlusion tests were performed on 15 surgical patients with pulmonary cancer. The relationship between these cardio-pulmonary parameters and exercise tolerance was studied, and pulmonary functional resectability was discussed. Pre- and post-operative anaerobic thresholds correlated with driving pressure (D.P: pulmonary artery pressure--pulmonary wedge pressure), and the pulmonary vascular-resistance index (PVRI). From the regression line and post-operative energy metabolic ratio, the standard limitation point of pulmonary resection can be estimated, (D.P = 22.6 mmHg PVRI = 621 dyne.sec.cm-5.m2). These data yielded a pulmonary pressure = 33.4 mmHg, total pulmonary vascular resistance index = 885 dyne.sec.cm-5.m2. These correlations were obtained because D.P and PVRI indicate the over all condition of the pulmonary vascular bed, gas exchange, ventilation and cardiac function. These data were in close agreement with previous results pertaining to the above indications. Unilateral pulmonary occlusion testing predicted the post-operative exercise tolerance of patients undergoing lung resection.

[A case of pulmonary actinomycosis that was difficult to distinguish from pulmonary carcinoma].

A 45-year-old male was admitted with chief complaint of hemoptysis. Prior to admission, a tumor in the S3 segment of the right lung had been detected by chest radiography. Despite a detailed examination after admission, no definite diagnosis was made, and right upper lobectomy was performed. Histopathological examination of the surgically resected tissue led to the diagnosis of pulmonary actinomycosis. In Japan, 52 cases of this condition were reported between 1964 and 1991. This paper discusses the epidemiology, diagnosis and diagnostic imaging of the condition, with reference to the literature.

Effect of birth season on case fatality rate of pulmonary tuberculosis: coincidence or causality?

The effects of birth season on the case fatality rate (CFR) of pulmonary tuberculosis were examined in case records of 9206 patients discharged during 1937-1965 from a national hospital for tuberculosis in Tokyo. The CFR was over 60% until 1945, then it decreased down to less than 9% after 1950. Male cases had little variation in their CFR by their birth season, while female cases had a significant variation and showed a significantly higher CFR than the male cases when they were born in January-June. The results suggest that the birth season had a significant influence on the prognosis of pulmonary tuberculosis.

[A case report of coronary artery bypass surgery (3-SVG) in 80-year-old woman with acute respiratory failure].

A successful operation for a patient of unstable angina with hypoxia is reported. A 80-year-old woman was admitted with severe chest oppression. The selective coronary angiogram revealed 3-vessel disease. Symptoms were uncontrolled by medical therapy. Aorto-coronary bypass surgery (with 3-saphenous vein grafts) was followed by excellent post-operative course. The patient has been asymptomatic for more than 1 year after operation.

Twinning in New England in the 17th-19th centuries.

Vital records of Saybrook and Plymouth in New England from the 17th century were investigated. Among 8,562 maternities 81 twin maternities were found, the twinning rate being 0.95%. Twinning rate was low at the 1st and 2nd births as compared with the 3rd or later births, and was highest at the 7th and 8th births (1.6%). Twin maternity seemed to be a strong risk factor to terminate reproduction, particularly after 6 or more children had been delivered. The rate of mothers who had any other child ("fertile" mothers) at the 7th or later birth order was significantly lower for twin (13%) than for singleton maternities (63%). Twinning rate also varied by the size of offspring of a mother, and those mothers who had 5 or 6 children showed the highest twinning rate (1.3%). Those fertile mothers who had 7 or more children showed the lowest twinning rate (0.74%), although an exceptionally higher twinning rate was seen at their last births. Elongation of the last birth interval was observed for each group of every family size, and higher twinning rates were generally observed at their last births. Reduction in fecundity and rise in twinning rate seem to have occurred simultaneously at the last stage of the reproductive period of mothers, regardless of their family size.