Preoperative evaluation of pleural adhesions with dynamic chest radiography: a retrospective study of 146 patients with lung cancer.

AIM: To assess the utility of dynamic chest radiography (DCR) during the preoperative evaluation of pleural adhesions. MATERIALS AND METHODS: Sequential chest radiographs of 146 patients with lung cancer were acquired during forced respiration using a DCR system. The presence of pleural adhesions and their grades were determined by retrospective surgery video assessment (absent: 121, present: 25). The maximum inspiration to expiration lung area ratio was used as an index for air intake volume. A ratio of ≥0.65 was regarded as insufficient respiration. Two radiologists assessed the images for pleural adhesions based on motion findings. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were compared for each adhesion grade and patient group (patients with sufficient/insufficient respiration). Pearson's chi-squared test compared the group. Statistical significance was set at p<0.05. RESULTS: DCR correctly identified 22/25 patients with pleural adhesions, with 20 false-positive results (sensitivity, 88%; specificity, 83.5%; PPV, 52.4%; NPV, 97.12%). Although the diagnostic performances for the various adhesion grades were similar, specificity in patients with sufficient respiration increased to 93.9% (31/33), identifying all cases except for those with loose adhesions. CONCLUSIONS: DCR images revealed restricted and/or distorted motions in lung structures and structural tension in patients with pleural adhesions. DCR could be a useful technique for routine preoperative evaluation of pleural adhesions. Further development of computerised methods can assist in the quantitative assessment of abnormal motion findings.

Epidemiology of massive hepatocellular carcinoma in dogs: A 4-year retrospective study.

Hepatocellular carcinoma (HCC) is the most common primary liver tumour in dogs. However, the clinical features and risk factors of HCC have not been confirmed. The objective of this study was to investigate the clinical features and risk factors for canine HCC. Medical records of 44 dogs diagnosed with HCC at Hokkaido University Veterinary Teaching Hospital between 2013 and 2017 were retrospectively reviewed. All dogs evaluated at the teaching hospital during the study period were used as the reference population for breed, age, sex predispositions or possible related factors for HCC, including concurrent disorders. Clinical characteristics of HCC were determined using propensity score matching analysis. The prevalence of HCC diagnosis was 0.96%. Multivariate analysis revealed that dogs diagnosed with HCC were significantly older (odds ratio [OR], 1.20; 95% confidence intervals [CI], 1.07-1.33) than the reference population. Welsh Corgis (OR, 3.68; 95% CI, 1.56-8.67) and Beagles (OR, 4.33; 95% CI, 1.58-11.90) were significantly predisposed to HCC. Twenty-seven of 44 dogs with HCC had at least one concurrent disorder. The most common concurrent disorder was hyperadrenocorticism (n = 10), and the adjusted odds of hyperadrenocorticism in dogs with HCC were 4.13 higher than those of the reference population (95% CI, 1.95-8.76). Propensity score matching analysis revealed that thrombocytosis (n = 30/43), increased alanine aminotransferase (n = 41/44), increased alkaline phosphatase (n = 42/44), and hypercalcemia (n = 13/32) were significantly associated with HCC diagnosis. The results of this study suggest that Welsh Corgis and Beagles are breeds with a predisposition for HCC and that hyperadrenocorticism might be a potential risk factor.

Indomethacin-induced generation of reactive oxygen species leads to epithelial cell injury before the formation of intestinal lesions in mice.

Recently, with the increasing number of elderly patients who continuously take aspirin and/or nonsteroidal anti-inflammatory drugs (NSAIDs), the number of cases of severe hemorrhagic gastrointestinal (GI) bleeding is also on the increase. Gastric acid has been reported to play the most important role in hemorrhagic gastric mucosal injury. However, the pathogenesis of NSAID-derived mucosal injury in the intestine, where there is no acidic environment, remains unknown. We previously reported that NSAID-derived mitochondrial reactive oxygen species (ROS) are directly involved in GI cellular injury in vitro, although an in vivo study has not yet been carried out. In this study, we investigated the relationship between NSAID-derived ROS and intestinal injury formation. For this purpose, intestinal mucosal live imaging in mice was carried out using an ROS-indicating fluorescent probe. Treatment with indomethacin caused macroscopic intestinal injury in mice; however, many dying cells were observed even in areas that macroscopically appeared to have no injury after treatment with indomethacin. A fluorescent probe revealed that mucosal cells in the apparently uninjured areas had a high concentration of ROS. Treatment with rebamipide significantly decreased both the ROS concentration and the number of dying cells: this drug is prescribed clinically for gastric injury patients and has been reported to upregulate the expression of manganese superoxide dismutase. On the basis of these results, we propose that NSAID treatment causes a high cellular concentration of ROS in mucosae, possibly decreasing mucosal organo-protective efficacy. Moreover, intestinal food contents are likely to damage the mucosal structure when it is in such a fragile condition.

Forkhead transcription factor FOXF1 is a novel target gene of the p53 family and regulates cancer cell migration and invasiveness.

p53 is an established tumor suppressor that can activate the transcription of multiple target genes. Recent evidence suggests that p53 may contribute to the regulation of cell invasion and migration. In this study, we show that the forkhead box transcription factor FOXF1 is a novel target of the p53 family because FOXF1 is upregulated by p53, TAp73 and TAp63. We show that FOXF1 is induced upon DNA damage in a p53-dependent manner. Furthermore, we identified a response element located within the FOXF1 gene that is responsive to wild-type p53, TAp73ß and TAp63γ. The ectopic expression of FOXF1 inhibited cancer cell invasion and migration, whereas the inactivation of FOXF1 stimulated cell invasion and migration. We also show that FOXF1 regulates the transcriptional activity of E-cadherin (CDH1) by acting on its FOXF1 consensus binding site located upstream of the E-cadherin gene. Collectively, our results show that FOXF1 is a p53 family target gene, and our data suggest that FOXF1 and p53 form a portion of a regulatory transcriptional network that appears to have an important role in cancer cell invasion and migration.

The relationship between anagliptin concentration showing over 80% inhibition of plasma dipeptidyl peptidase-4 activity and its protective effect against glucagon-like peptide-1 degradation.

In dipeptidyl peptidase-4 (DPP-4) inhibitors, the inhibition of plasma DPP-4 activity by 80% is considered sufficient to have an effect on glycemic control improvement through the elevation of intact glucagon-like peptide-1 (GLP-1). To clarify whether or not the 80% inhibition is sufficient to protect against GLP-1 degradation, we investigated rats with a continuous infusion of exogenous GLP-1. When GLP-1 was infused into the femoral or portal vein, the steady state active GLP-1 levels in plasma significantly increased (P<0.05) at the 80% inhibitory concentration (IC80) of anagliptin (a highly selective DPP-4 inhibitor) against plasma DPP-4 activity, compared with control. In addition, the peptide levels increased in a concentration-dependent manner at drug concentrations from IC80 to 10-fold IC80, and the levels at the 10-fold IC80 were significantly higher (P<0.05) than those at IC80. The concentration dependency on GLP-1 increment was also confirmed based on the experiment in which the endogenous active GLP-1 levels were measured after an oral carbohydrate load. These findings suggest that an almost complete inhibition (80%) of plasma DPP-4 activity was insufficient to protect GLP-1 degradation, and much higher drug concentrations such as 10-fold IC80 are necessary to potently protect GLP-1 from degradation by DPP-4 commonly present in blood and tissues.

Salt is an oxidative stressor for gastric epithelial cells.

Salt/NaCl has been reported to induce necrosis in gastric mucosal cells, however, the mechanisms for gastric injury by salt are not clarified. In this study, we elucidated whether salt is an oxidative stress inducer via mitochondrial injury on rat gastric epithelial cells (RGM-1) in 300, 450, 650 and 1000 mM of NaCl-contained medium. To clarify whether salt-induced reactive oxygen species (ROS) is derived from mitochondria, we also investigated a salt-induced ROS production in manganese superoxide dismutase overexpressing cells (RGM-MnSOD). MnSOD is a specific scavenger for superoxide anion produced from mitochondria. The results showed that cellular injuries in RGM-MnSOD were significantly less severe than that in normal RGM-1. The electron paramagnetic resonance (EPR) studies also provided an evidence that the salt-derived superoxide production in RGM-MnSOD was less than that in normal RGM-1. These results indicated that salt is not merely a necrotizing factor for gastric epithelial cells, but also an oxidative stress inducer.

Long interspersed element-1 is differentially regulated by food-borne carcinogens via the aryl hydrocarbon receptor.

A single human cell contains more than 5.0 × 10(5) copies of long interspersed element-1 (L1), 80-100 of which are competent for retrotransposition (L1-RTP). Recent observations have revealed the presence of de novo L1 insertions in various tumors, but little is known about its mechanism. Here, we found that 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3,8-dimethyl-imidazo[4,5-f]quinoxaline (MeIQx), food-borne carcinogens that are present in broiled meats, induced L1-RTP. This induction was dependent on a cellular cascade comprising the aryl hydrocarbon receptor (AhR), a mitogen-activated protein kinase, and CCAAT/enhancer-binding protein ß. Notably, these compounds exhibited differential induction of L1-RTP. MeIQx-induced L1-RTP was dependent on AhR nuclear translocator 1 (ARNT1), a counterpart of AhR required for gene expression in response to environmental pollutants. By contrast, PhIP-induced L1-RTP did not require ARNT1 but was dependent on estrogen receptor α (ERα) and AhR repressor. In vivo studies using transgenic mice harboring the human L1 gene indicated that PhIP-induced L1-RTP was reproducibly detected in the mammary gland, which is a target organ of PhIP-induced carcinoma. Moreover, picomolar levels of each compound induced L1-RTP, which is comparable to the PhIP concentration detected in human breast milk. Data suggest that somatic cells possess machineries that induce L1-RTP in response to the carcinogenic compounds. Together with data showing that micromolar levels of heterocyclic amines (HCAs) were non-genotoxic, our observations indicate that L1-RTP by environmental compounds is a novel type of genomic instability, further suggesting that analysis of L1-RTP by HCAs is a novel approach to clarification of modes of carcinogenesis.

High loss to follow-up following obstetric fistula repair surgery in rural Burundi: is there a way forward?

SETTING: Gitega Fistula Centre (GFC), a dedicated obstetric fistula repair centre providing comprehensive care at the Gitega District Hospital, rural Burundi. OBJECTIVES: To describe 1) the proportion who returned for scheduled 3- and 6-month follow-up visits and 2) outcomes (fistula closure rates and continence status) at discharge from hospital and after 3 and 6 months among patients who underwent fistula repair surgery. DESIGN: Retrospective cohort analysis using programme data from April 2010 to December 2011. RESULTS: A total of 475 women with obstetric fistula underwent surgical repair. At discharge from hospital, 415 (87%) had a closed fistula, of whom 318 (77%) were continent of urine and/or faeces, while 97 (23%) remained incontinent despite closure. Of the 415 patients with closed fistula, only 244 (59%) were followed up at 3 months and 73 (18%) at 6 months (χ(2) for linear trend 576, P < 0.0001). This indicates progressive loss to follow-up, reaching 82% by 6 months. CONCLUSION: Women undergoing obstetric fistula repair surgery at GFC achieve good hospital exit outcomes. Thereafter, substantial and progressive loss to follow-up hinder the ability to judge programme success over time. Steps to address this operational problem are discussed.

A novel approach to cancer treatment using structural hybrids of the p53 gene family.

The p53 tumor suppressor belongs to a gene family that includes two other structurally and functionally related members: p73 and p63. The regulation of p53 activity differs significantly from that of p73 and p63. To enhance the tumor suppressive activity of p53, we constructed six recombinant adenoviruses that encode hybrid proteins with three functional domains derived from either p53 or TAp63γ. The potency of these hybrid molecules in suppressing tumorigenesis was evaluated using in vitro and in vivo models. Of the hybrid molecules tested, one hybrid named p63-53O was the most potent activator of apoptosis in human cancer cells. The p63-53O hybrid is composed of the transcriptional activation domain and DNA-binding domain of TAp63γ and the oligomerization domain of p53. The p63-53O hybrid efficiently transactivated p53AIP1. Moreover, silencing of p53AIP1 partially abolished the apoptotic response to p63-53O in human cancer cells. The p53-p63 hybrid molecule is a novel potent anti-proliferative agent for the treatment of cancer.

Rebamipide attenuates nonsteroidal anti-inflammatory drugs (NSAID) induced lipid peroxidation by the manganese superoxide dismutase (MnSOD) overexpression in gastrointestinal epithelial cells.

Nonsteroidal anti-inflammatory drugs (NSAIDs) often cause gastrointestinal complications such as gastric ulcers and erosions. Recent studies on the pathogenesis have revealed that NSAIDs induce lipid peroxidation in gastric epithelial cells by generating superoxide anion in mitochondria, independently with cyclooxygenase-inhibition and the subsequent prostaglandin deficiency. Although not clearly elucidated, the impairment of mitochondrial oxidative phosphorylation, or uncoupling, by NSAIDs is associated with the generation of superoxide anion. Physiologically, superoxide is immediately transformed into hydrogen peroxide and diatomic oxygen with manganese superoxide dismutase (MnSOD). Rebamipide is an antiulcer agent that showed protective effects against NSAID-induced lipid peroxidation in gastrointestinal tracts. We hypothesized that rebamipide may attenuate lipid peroxidation by increasing the expression of MnSOD protein in mitochondria and decreasing the leakage of superoxide anion in NSAID-treated gastric and small intestinal epithelial cells. Firstly, to examine rebamipide increases the expression of MnSOD proteins in mitochondria of gastrointestinal epithelial cells, we underwent Western blotting analysis against anti-MnSOD antibody in gastric RGM1 cells and small intestinal IEC6 cells. Secondly, to examine whether the pretreatment of rebamipide decreases NSAID-induced mitochondrial impairment and lipid peroxidation, we treated these cells with NSAIDs with or without rebamipide pretreatment, and examined with specific fluorescent indicators. Finally, to examine whether pretreatment of rebamipide attenuates NSAID-induced superoxide anion leakage from mitochondria, we examined the mitochondria from indomethacin-treated RGM1 cells with electron spin resonance (ESR) spectroscopy using a specific spin-trapping reagent, CYPMPO. Rebamipide increased the expression of MnSOD protein, and attenuated NSAID-induced mitochondrial impairment and lipid peroxidation in RGM1 and IEC6 cells. The pretreatment of rebamipide significantly decreased the signal intensity of superoxide anion from the mitochondria. We conclude that rebamipide attenuates lipid peroxidation by increasing the expression of MnSOD protein and decreasing superoxide anion leakage from mitochondria in both gastric and small intestinal epithelial cells.

Tissue rinse liquid-based cytology: a feasible tool for the intraoperative pathological evaluation of sentinel lymph nodes in breast cancer patients.

OBJECTIVES: A unique diagnostic method was designed for the intraoperative pathological evaluation of sentinel lymph nodes (SLNs) in breast cancer patients, and the results were verified with 2 years of experience. METHODS: Excised lymph nodes were cut into 2-mm-thick slices and rinsed thoroughly in CytoRich Red(®). The sliced tissues were embedded in a paraffin block. Three cytological glass slides of the cells exfoliated in CytoRich Red(®) were prepared by the SurePath(®) liquid-based cytology (LBC) technique. Two slides were stained by the Papanicolaou method, and the remaining slide was immunostained with an anti-keratin antibody. This process is called tissue rinse liquid-based cytology (TRLBC). The results of TRLBC were compared with those of the final pathological diagnoses, including immunostaining with an anti-keratin antibody on paraffin blocks (PB). RESULTS: This study analysed 444 SLNs from 247 consecutive breast cancer patients. It required 35 minutes to complete the intraoperative diagnosis on a single node, and it took an additional 5 minutes per node if more than one node was submitted. When the results of PB were assumed to be the gold standard, the sensitivity and specificity of TRLBC were 81.9% and 96.1%, respectively. TRLBC detected all nodes with macrometastasis and 23 of 24 nodes with micrometastasis. Fifteen false-negative TRLBC results were 'isolated tumour cell clusters' on PB, but there was one with micrometastasis histologically. Four of 14 false-positive TRLBC results were proven to be true positive by supplementary examination using step sectioning of the paraffin blocks of the nodes. CONCLUSION: TRLBC is a feasible and promising intraoperative cytopathological tool showing a comparable efficacy to PB while still allowing the conventional postoperative histological examination.

Apple pectin affects the efficacy of epigallocatechin gallate on oral sucrose tolerance test in adult mice.

Epigallocatechin gallate (EGCg), a dietary polyphenol and a major tea catechin, is a known sucrase inhibitor. Since dietary pectin is known to modulate some of the functions of the gastrointestinal tract, we investigated whether it could specifically affect the efficacy of EGCg on an oral sucrose tolerance test in mice. Male Crj:CD-1 (ICR) mice (seven weeks old) were randomly divided into two groups and fed a 5 % apple pectin (PE) or 5 % cellulose (CE) diet (control diet) for 28 days. After the experimental diet period, all mice were fasted overnight. A volume of 0.2 mL EGCg (20 mg/mL) was orally administered to all the mice by stainless steel feeding needle via injection syringe and a sucrose tolerance test was performed. The blood glucose levels were measured in blood collected from the tail vein using the OneTouch® Ultra® blood glucose monitoring system. Blood glucose levels at 30 minutes and 60 minutes after sucrose loading in the PE group were significantly higher than initial blood glucose levels. However, blood glucose levels at 30 minutes, 60 minutes, and 120 minutes after sucrose loading in the CE group were not significantly higher than initial blood glucose levels. After laparotomy, plasma lipids were also measured. Plasma triglyceride concentrations were significantly greater in the PE group than in the CE (control) group. This demonstrates that dietary pectin can affect the efficacy of EGCg on the oral sucrose tolerance test in mice.

"Donut's shape" radiosurgical treatment planning for large cystic metastatic brain tumors.

BACKGROUND: Radiosurgical management of large cystic metastatic brain tumors represents a significant challenge. Nevertheless, modified dose planning has shown beneficial results in such cases. METHOD AND RESULTS: "Donut's shape" radiosurgical treatment planning is based on the chain-like application of multiple, small-sized isocenters for selective coverage of the contrast-enhancing tumor capsule and minimal irradiation of the central cystic area. Such an approach was used for the management of large cystic intracranial metastases, which were not accompanied by a significant mass effect and did not require immediate volume reduction. Treatment was done using Leksell Gamma Knife model C with automatic positioning system. The majority of treated lesions showed significant shrinkage after radiosurgery and no major complications were met. CONCLUSION: Large cystic metastatic brain tumors may be successfully treated with gamma knife radiosurgery alone using the proposed "donut's shape" dose planning with coverage of the contrast-enhancing tumor capsule by multiple small-sized isocenters.

[Primary anterior mediastinal huge lipoma: report of a case].

We report a case of anterior mediastinal lipoma. A 71-year-old female was admitted for cough. A fat density tumor from anterior mediastinum to left thoracic cavity was found by chest X-ray, chest computed tomography (CT) and magnetic resonance imaging (MRI). Defect of left dorsal diaphragm was suspected and there was a possibility that the tumor was connected to retroperitoneum. Under the preoperative diagnosis of a benign huge mediastinal lipoma, we conducted an operation. At 1st, we observed by thoracoscopy and made sure that the mass was primary anterior mediastinal tumor and not connected to retroperitoneum. Through the median sternotomy, we completely resected the tumor with thymus. The tumor showed 27 cm in diameter, and histopathological diagnosis of the tumor was benign lipoma. Lipoma of the mediastinum is very rare and about 0.3% of all mediastinal tumors. It is sometimes difficult to distinguish huge lipoma from liposarcoma only by clinical examinations such as CT scan or MRI. We evaluated the condition of the tumor by thoracoscopic observation, and the tumor was safely and completely resected by median sternotomy.

The effect of gantry and collimator angles on leaf limited velocity and position in dynamic multileaf collimator intensity-modulated radiation therapy.

The purpose of the study is to evaluate the limiting velocity (LV) of a multileaf collimator and the leaf position in various collimator and gantry angles. Both leading leaves and trailing leaves began to move with a constant acceleration from 0 to 4 cm s(-1). When the beam hold occurred, the leaf velocity was defined as the leaf LV. Dynamic irradiation was performed at eight gantry angles of every 45 degrees with three different collimator angles. The analysis of the LV and the leaf position was performed with a log file from a leaf motion controller. The mean LVs for Varian Clinac 21EX (21EX) ranged from 2.51 to 3.10 cm s(-1). The mean LVs for Clinac 600C ranged from 2.91 to 3.12 cm s(-1). When only central 5 mm leaves of 21EX moved, LVs were significantly higher than those when all 60 pairs of leaf moved, while the leaf position inconsistencies of the two accelerators were within 1 mm at the leaf velocities from 0.5 to 2.0 cm s(-1). It was recognized that the LV was affected by gravity. This measurement method can be utilized as routine quality assurance for a dynamic multileaf collimator (DMLC) is and easily reproducible.

The elderly patients on hemodialysis.

Nephrologists care for an increasing number of elderly patients on hemodialysis. As such, an understanding of the overlap among complications of hemodialysis and geriatric syndromes is crucial. This article reviews hemodialysis management issues including vascular access, hypertension, anemia and bone and mineral disorders with an attention towards the distinct medical needs of the elderly. Key concepts of geriatrics frailty, dementia and palliative care are also discussed, as nephrologists frequently participate in decision-making directed toward balancing longevity, functional status and the burden of therapy.

[Video-assisted thoracic surgery for clinical stage I lung cancer].

We evaluated our results of video-assisted thoracic surgery (VATS) performed for lung cancer over 8 years. Between April 2000 and October 2008, a total of 409 (60.9%) underwent VATS for lung cancer. Operative procedures as a radical operation were partial resection in 58 patients, segmentectomy in 64 patients, and lobectomy in 229 patients. There was 1 patient with operative death including hospital death due to pulmonary thromboembolism. In a median follow-up period of 21 months, the 5-year cause specific survival rate was 93.7%. According to operative procedures, the 5-year survival rate was 100% in patients underwent partial resection and segmentectomy, and 91.1% in patients underwent lobectomy. According to pathological stages, the 5-year survival rate was 98.8% in 289 patients with stage IA, 69.1% in 34 patients with stage IB, and 68.2% in 14 patients with stage IIIA. In conclusion, VATS lobectomy and VATS intentional limited resection can be performed with low mortality and good prognosis for clinical stage IA lung cancer patients.

[Gastrointestinal hemorrhage induced by percussive ventilator in an infant with chronic lung disease complicated after surgery for corrected transposition of the great arteries].

A newborn patient (birth weight 2,332 g) with corrected transposition of the great arteries developed chronic lung disease due to a severe heart failure and post operative several complications. We applied intrapulmonary percussive ventilation (IPV) to the patient. IPV improved oxygenation concomitant with the improvement of respiratory condition and chest X-ray finding. However, the patient suffered from upper gastrointestinal bleeding 15 days after initiation of IPV therapy. The bleeding was healed several days after temporal termination of IPV, but recurred with resuming IPV therapy. The patient was irritable throughout the IPV therapy, and thus gastrointestinal bleeding of the patient could be due to stress induced by IPV therapy. IPV may be useful for the management of respiratory disturbance, often observed in low birth weight patients with congenital heart defects. However, gastrointestinal bleeding may occur and should be considered as a possible complication associated with IPV therapy.

Multipotency of clonal cells derived from swine periodontal ligament and differential regulation by fibroblast growth factor and bone morphogenetic protein.

BACKGROUND AND OBJECTIVE: A blood supply is indispensable for the regeneration of damaged or lost periodontal ligament (PDL) tissue. Mesenchymal stem cell-like activity of cells derived from the PDL has been identified by their capacity to form fibrous and osseous tissue and cementum. However, it remains to be clarified whether the cells have an ability to build the capillary network of blood vessels. This study evaluated the potential of cells derived from the PDL to construct a blood vessel-like structure and examined how growth factors controlled the multipotency of the cells. MATERIAL AND METHODS: The ability of a swine PDL fibroblast cell line, TesPDL3, to construct a blood vessel-like structure was evaluated on and in the self-assembling peptide scaffold, PuraMatrix(TM). In addition, the ability of the cells to form mineralized nodules was evaluated on type I collagen-coated plastic plates. In some cases, fibroblast growth factor (FGF)-2 and bone morphogenetic protein (BMP)-2 were added to these cultures. The status of the expression of vascular and osteoblastic cell-specific markers in the cells was evaluated using reverse transcriptase-polymerase chain reaction (RT-PCR), Western blotting and immunofluorescence analyses. RESULTS: The TesPDL3 cells not only formed mineralized nodules in response to BMP-2 stimulation but also constructed tube-like structures in response to FGF-2 stimulation. Intriguingly, FGF-2 inhibited the BMP-2-induced formation of mineralized nodules. Conversely, BMP-2 inhibited the FGF-2-induced formation of tube-like structures. CONCLUSION: Periodontal ligament fibroblasts have the potential to differentiate not only into osteoblastic but also into vascular cell lineages. The destiny of the cells was reciprocally regulated by BMP-2 and FGF-2.