GH safety workshop position paper: a critical appraisal of recombinant human GH therapy in children and adults.

Recombinant human GH (rhGH) has been in use for 30 years, and over that time its safety and efficacy in children and adults has been subject to considerable scrutiny. In 2001, a statement from the GH Research Society (GRS) concluded that 'for approved indications, GH is safe'; however, the statement highlighted a number of areas for on-going surveillance of long-term safety, including cancer risk, impact on glucose homeostasis, and use of high dose pharmacological rhGH treatment. Over the intervening years, there have been a number of publications addressing the safety of rhGH with regard to mortality, cancer and cardiovascular risk, and the need for long-term surveillance of the increasing number of adults who were treated with rhGH in childhood. Against this backdrop of interest in safety, the European Society of Paediatric Endocrinology (ESPE), the GRS, and the Pediatric Endocrine Society (PES) convened a meeting to reappraise the safety of rhGH. The ouput of the meeting is a concise position statement.

[Lung resection for patients with lung cancer and chronic obstructive pulmonary disease].

The number of lung resection for patients with lung cancer has been increasing lineally for last two decades in Japan. It reached more than 30,000 in 2009. Subsequently those combined with chronic obstructive pulmonary disease (COPD) also have increased. As pulmonary vascular bed has already been lost to some extent due to chronic alveolar destruction, a careful preoperative physiologic assessment according to a guideline by American College of Chest Physicians (ACCP) or European Respiratory Society( ERS)/European Society of Thoracic Surgeons( ESTS) is important to select patients to be underwent lung resection within acceptable risk. The process to evaluate the risk of lung resection for a lung cancer patient has three steps structured by forced expiratory volume in 1 sec( FEV1), diffusion capacitiy for carbon monoxide (DLco), and exercise capacity. We suggested that it would be more practical to add global initiative for obstructive lung disease( GOLD) staging of each patient and distribution of emphysematous lung obtained by functional imaging modarities to the pathway of flow chart of the guideline. Some patients with very low FEV1 demonstrate increase in FEV1 after lung resection by so called lung volume reduction effect. To utilize lots of findings and experiences obtained from lung volume reduction surgery( LVRS) contributes to select patients with lung cancer and COPD and to perform lung resection and perioperative care properly.

[Surgery for emphysematous giant bullae].

We address 3 important keys to obtain successful outcomes in surgery for emphysematous giant bullae. It is the 1st step to select patients who might benefit from bullectomy based on functional imaging. The chest computed tomography (CT) and pulmonary perfusion scintigram provide information regarding with pulmonary vascular beds which could be recruited by bullectomy. In addition, dynamic-magnetic resonance imaging (MRI) during breathing can show a patient with paradoxical inflation of giant bulla during expiration, which means impairment of ventilation of the adjacent normal parenchyma, and is a promising sign for successful outcome of bullectomy. Second, it should be emphasized to perform a proper procedure in bullectomy. If a giant bulla has a wide bottom, it should be recommended to open the bulla and to plicate it by sutures without injury of vessels on the bottom of the bulla rather than simple bullectomy with staples. Finally, it is important to keep inflated lung avoiding atelectasis following operation by minimum pressure of suction. We show here sequential bullectomies on a 41-year-old male with chronic obstructive pulmonary disease (COPD) GOLD IV due to bilateral giant bullae and poor vascular reserve, and address our strategy described above.

[Surgical treatment for tumors in the superior sulcus].

Surgical challenge for tumors arising posterior-apical lung well known as Pancoast tumor and those of the apical lung involving anterior thoracic outlet structures (mainly subclavian vessels) have been continued with seeking the pathway of the proper approaches and the strategy combined modalities as radiotherapy or chemoradiotherapy followed by surgery for these 50 years, and operative outcome have been improved these decades. As complete resection of the tumors is the main factor for operative results, the preoperative evaluation on involved structures and the choice among the different approaches is important. We present our experience for Pancoast tumors with posterior approaches and for cervico-thoracic tumors resected with anterior approaches.

Statin suppresses apoptosis in osteoblastic cells: role of transforming growth factor-beta-Smad3 pathway.

Statins possess pleiotropic effects in several tissues. Among them, their bone anabolic actions have been recently noted. We have proposed that Smad3, a TGF-beta-signaling molecule, is a promoter of bone formation. However, whether statins would affect TGF-beta-Smad3 pathway in osteoblasts is still unknown. The present study was performed to examine the effects of statin on Smad3 expression and cell apoptosis by employing mouse osteoblastic MC3T3-E1 and rat osteoblastic UMR-106 cells. Statins (pitavastatin, mevastatin, and simvastatin) as well as alendronate increased the levels of Smad3 in MC3T3-E1 cells. The effects of pitavastatin on Smad3 levels were observed from 3 hours and later. Pitavastatin induced the expression of TGF-beta, and cycloheximide, a protein synthesis inhibitor, antagonized the increased levels of pitavastatin on Smad3. On the other hand, pitavastatin antagonized dexamethasone- or etoposide-induced apoptosis in a dose-dependent manner, and Smad3 inactivation by dominant negative Smad3 or an inhibition of endogenous TGF-beta action by SB431542 antagonized anti-apoptotic effects of pitavastatin, indicating that pitavastatin suppressed osteoblast apoptosis partly through TGF-beta-Smad3 pathway. In conclusion, the present study has demonstrated for the first time that statin suppressed cell apoptosis partly through TGF-beta-Smad3 pathway in osteoblastic cells.

Safety and efficacy of growth hormone (GH) during extended treatment of adult Japanese patients with GH deficiency (GHD).

OBJECTIVES: To assess the effects of a growth hormone (GH) replacement therapy using a GH dose regimen based on serum insulin-like growth factor (IGF-I) concentrations in Japanese adults with GH deficiency (GHD). DESIGN: In this multicentre, uncontrolled, open-label study, Japanese adults with GHD who had received either GH replacement therapy (GH-GH group, n=35) or placebo (Placebo-GH group, n=36) in a previous randomised, double-blind, placebo-controlled trial were treated with GH replacement therapy for 48 weeks. GH treatment was started at a dose of 0.003 mg/kg/day administered by subcutaneous injection for the first 8 weeks, after which the dose was adjusted to maintain patients' serum IGF-I levels within the reference range adjusted for age and gender. Body composition, serum lipids, serum IGF-I and IGF binding protein-3 (IGFBP-3) levels were measured throughout study. Symptom and quality of life scores were also determined. RESULTS: Lean body mass (LBM) was increased compared with baseline (the end of the preceding double-blind trial) at 24 and 48 weeks, with a mean (+/-SD) increase of 1.3% (+/-4.2%) at week 48 in the GH-GH group (an increase of 6.6% [+/-6.0%] from the start of the preceding double-blind trial) and a larger increase of 4.7% (+/-5.9%) in the Placebo-GH group. Body fat mass (BFM) increased slightly from baseline in the GH-GH group with a mean increase of 2.9+/-10.6% at week 48 (a decrease from the start of the preceding double-blind trial at 48 weeks of 7.8% [+/-15.0%]) but decreased by 6.5% (+/-11.7%) at week 48 in the Placebo-GH group. Serum lipids were unchanged or slightly increased from baseline in the GH-GH group but patients' lipid profiles improved in the Placebo-GH group. In patients who received placebo during the double-blind study, individualised GH therapy in this open-label study increased mean LBM at 48 weeks by 6.2+/-6.8% in patients with CO GHD and by 3.0+/-4.4% in patients with AO GHD. Changes in mean LBM and mean BFM at week 48 were +4.1+/-4.5% and -2.4+/-10.5%, respectively, in females and +5.0+/-6.7% and -8.9+/-11.8%, respectively, in males. In patients who received GH treatment during the double-blind study, overall changes in LBM, BFM and IGF-I SD score after 24 weeks and 48 weeks were small, with no significant differences between subgroups. While the overall incidence of adverse events was broadly similar in the GH-GH and Placebo-GH groups (97% and 89%, respectively), the incidence of treatment-related events was higher in the GH-GH group (83% vs 42% in the Placebo-GH group). Most adverse events in both treatment groups were of mild or moderate severity and not clinically significant. The incidences of oedema and cases of high IGF-I during the IGF-I level-adjusted treatment regimen were lower than those during the preceding fixed dose titration. CONCLUSION: Long-term GH replacement therapy was well tolerated in Japanese adults with GHD. GH treatment maintained the improvements in body composition and lipid profiles in the patients previously treated in the double-blind study (GH-GH group) and improved these parameters in previously untreated patients (Placebo-GH group). Individualised GH administration based on IGF-I levels was well-tolerated and effective.

Relationship between endogenous parathyroid hormone and bone metabolism/geometry in female patients treated with glucocorticoid.

Although the role of PTH (parathyroid hormone) has been debated in glucocorticoid (GC)-induced osteoporosis (GIO), clinical data about the relation of endogenous PTH to bone metabolism in patients treated with GC are still lacking. The present study was performed to examine the relationship of PTH to bone metabolic indices, bone mineral density (BMD), and bone geometry in 174 female patients treated with oral GC for more than 6 months. Dual-energy X-ray absorptiometry and peripheral quantitative computed tomography (pQCT) were employed for the assessment of BMD and bone geometry. No elevation of serum PTH levels was observed in patients treated with GC. Although serum levels of osteocalcin were not related to serum PTH levels, urinary levels of deoxypiridinoline were positively correlated. Serum PTH levels were negatively related to BMD at any site. In pQCT, serum PTH levels were negatively correlated to both trabecular and cortical volumetric BMD. As for bone morphometric indices, serum PTH levels were significantly related to endocortical circumferences, cortical thickness, and cortical area. Moreover, serum PTH levels were significantly higher in patients with vertebral fractures, compared with those without vertebral fractures in GC-treated patients. In the present study, serum PTH levels were related to the elevation of bone resorption marker, decreased BMD, cortical thinning, and an increase of vertebral fracture risk. The elevation of sensitivity to PTH in bone might play some role in the pathogenesis of GIO.

Serum soluble factors induce the proliferation, alkaline phosphatase activity and transforming growth factor-beta signal in osteoblastic cells in the patient with hepatitis C-associated osteosclerosis.

Hepatitis C-associated osteosclerosis (HCAO) is a rare syndrome characterized by severe, acquired, generalized osteosclerosis and hyperostosis in adults who are infected with the hepatitis C virus. However, the detail of the pathogenesis of HCAO is still unknown. We examined the effects of serum of the HCAO patient on the proliferation, alkaline phosphatase (ALP) activity and transforming growth factor (TGF)-beta-Smad signaling in mouse osteoblastic cells. The patient was compatible with HCAO, characterized by high bone mass, bone thickening and bone pain with normal lamelar bone. The serum from the HCAO patient increased the levels of TGF-beta and Smad3 expression in osteoblastic MC3T3-E1 cells, compared with the control subject. Moreover, the serum from the HCAO patient significantly augmented TGF-beta-induced transcriptional activity with luciferase assay using 3TP-Lux with a Smad3-specific responsive element. In addition, the serum from the HCAO patient significantly stimulated the MTT intensity, the level of proliferating cell nuclear antigen expression, a proliferation marker, and ALP activity in MC3T3-E1 cells, compared with that from the control subject. In conclusion, the present study indicated that the serum from the HCAO patient stimulated TGF-beta-Smad signaling, as well as the proliferation and ALP activity in osteoblastic cells. Some soluble factors other than parathyroid hormone might be related to the pathogenesis of HCAO.

[Preoperative antifungal agent for pulmonary aspergilloma].

A 52-year-old man with a 6-month history of bloody sputum was admitted to our hospital. Chest X-ray on admission showed a pulmonary cavity with liquid content in the left upper field and consolidation at the circumference of the lesion. Chest computed tomography (CT) on the 13th hospital day revealed a typical fungus ball in the cavity, which we diagnosed as pulmonary aspergilloma. We administered him micafungin sodium for 1 month. Voriconazole was administered subsequently, but side effects developed. Therefore, itraconazole was administered as a substitute. Chest high-resolution CT (HRCT) clearly showed a reduction in size of the aspergilloma, thus confirming the effectiveness of antifungal agent administration in this case. However, since hemoptysis occurred for the case, left upper lobectomy was performed and postoperative course was excellent.

Smad3 differently affects osteoblast differentiation depending upon its differentiation stage.

Smad3, a critical component of the TGF-beta signaling pathways, plays an important role in the regulation of bone formation. However, how Smad3 affects osteoblast at the different differentiation stage remains still unknown. In the present study, we examined the effects of Smad3 on osteoblast phenotype by employing mouse bone marrow ST-2 cells and mouse osteoblastic MC3T3-E1 cells at the different differentiation stage. Smad3 overexpression significantly inhibited bone morphogenetic protein-2 (BMP-2)-induced ALP activity in ST-2 cells, indicating that Smad3 suppresses the commitment of pluripotent mesenchymal cells into osteoblastic cells. Smad3 increased the levels of COLI and ALP mRNA at 7 day cultures in MC3T3-E1 cells, and its effects on COL1 were decreased as the culture periods progress, although its effects on ALP were sustained during 21 day cultures. Smad3 overexpression enhanced the level of Runx2 and OCN mRNA at 14 day and 21 day cultures. Smad3 increased the levels of MGP and NPP-1 mRNA, although the extent of increase in MGP and NPP-1 was reduced and enhanced during the progression of culture period, respectively. Smad3 did not affect the level of ANK mRNA. On the other hand, Smad3 enhanced the level of MEPE mRNA at 14 and 21 day cultures, although Smad3 decreased it at 7 day cultures. In conclusion, Smad3 inhibits the osteoblastic commitment of ST-2 cells, while promotes the early stage of differentiation and maturation of osteoblastic committed MC3T3-E1 cells. Also, Smad3 enhanced the expression of mineralization-related genes at the maturation phase of MC3T3-E1 cells.

The usefulness of bone metabolic indices for the prediction of changes in bone mineral density after parathyroidectomy in patients with primary hyperparathyroidism.

Patients with primary hyperparathyroidism (pHPT) have reduced bone mineral density (BMD). Although pHPT causes high bone turnover, the exact metabolic bone markers useful for predicting changes in BMD after parathyroidectomy (PTX) remain elusive. The present study was performed to examine the relationship between bone metabolic indices and BMD changes after PTX in 29 pHPT Japanese patients, which received PTX successfully. BMD values were measured by dual-energy X-ray absorptiometry in the lumbar spine and distal one third of radius. As for bone metabolic indices, serum bone-type alkaline phosphates (BAP), serum osteocalcin (OCN), urinary deoxypiridinoline (Dpd), and urinary type I collagen cross-linked N-telopeptides (NTX) were measured. The study included 10 male and 19 female patients (17 postmenopausal). Urinary Dpd, but not NTX was significantly correlated with serum BAP and OCN. Either bone formation or bone resorption indices were significantly and highly correlated with Z-score of BMD in the radius, but not at lumbar spine. Urinary Dpd was significantly correlated with BMD changes at both lumbar spine and radius and at all time points over the two years after PTX. These correlations were most potent among bone metabolic indices in this study. The measurement of urinary Dpd would be useful for predicting long-term changes in BMD at radial and lumbar spine after PTX than other bone metabolic indices.

Efficacy and safety of growth hormone (GH) in the treatment of adult Japanese patients with GH deficiency: a randomised, placebo-controlled study.

OBJECTIVE: The aim of this study was to assess the effect of growth hormone (GH) replacement therapy on lean body mass (LBM) and other variables including body fat mass, serum lipids and quality of life measures in GH-deficient Japanese adults. DESIGN: This was a multicentre, double-blind, placebo-controlled, parallel group study. Following initial screening, patients were randomly assigned to GH treatment (n=37) or placebo (n=36). GH treatment was started at an initial dose 0.003 mg/kg/day s.c. each day for the first 4 weeks after which the dose was increased to 0.006 mg/kg/day for 4 weeks and then to 0.012 mg/kg/day for the last 16 weeks (n=37). Body composition, serum lipids, serum IGF-I and IGFBP-3 levels were measured during the 24-week study. Short Form-36 and Quality of Life Assessment of GH Deficiency in Adults scores were also determined. RESULTS: LBM was significantly increased from baseline at 24 weeks in GH-treated patients, with a mean (+/-SD) increase of 4.7% (+/-5.3%) compared with an increase of 1.0% (+/-4.4%) in the placebo group (p<0.0001 versus baseline, p=0.0003 versus placebo). Percentage body fat decreased significantly from baseline in GH-treated patients (9.3%, p<0.0001), compared with a non-significant 0.2% increase in the placebo group (p<0.0004 for difference between treatment groups). In addition, significantly increased serum IGF-I and IGFBP-3 levels and improvements in the patients' serum lipid profiles were observed in patients who received GH therapy. Changes in quality of life measures did not differ between treatments, probably because of the small number of patients studied. GH therapy was well tolerated, with adverse events of any cause reported in 86.5% of the GH treatment group and 83.3% of the placebo group. CONCLUSION: GH treatment significantly improved body composition and serum lipid profiles in adult Japanese patients with GH deficiency compared with placebo and had no clinically relevant adverse effects.

Serum levels of insulin-like growth factor (IGF); IGF-binding proteins-3, -4, and -5; and their relationships to bone mineral density and the risk of vertebral fractures in postmenopausal women.

We previously found that serum levels of insulin-like growth factor I (IGF-I) and IGF-binding protein (IGFBP)-3, but not IFGBP-2, were associated with bone mineral density (BMD) and the risk of vertebral fractures. The aim of the present study was to investigate the roles of IGFBP-4 and -5 in age-dependent bone loss and vertebral fracture risk in postmenopausal Japanese women and to compare them with those of IGF-I and IGFBP-3. One hundred and ninety-three Japanese women aged 46-88 years (mean 62.5) were enrolled in the cross-sectional study. BMD was measured at the lumbar spine, femoral neck, ultradistal radius (UDR), and total body by dual-energy X-ray absorptiometry. Serum levels of IGFBP-4 and -5 as well as IGF-I and IGFBP-3 were measured by radioimmunoassay. Serum levels of IGF-I, IGFBP-3, and IGFBP-5 declined with age, while serum IGFBP-4 increased with age. Multiple regression analysis was performed between BMD at each skeletal site and serum levels of IGF-I and IGFBPs adjusted for age, body weight, height, and serum creatinine. BMD at the UDR was significantly and positively correlated with all serum levels of IGF-I and IGFBPs measured (P < 0.01), while BMD at the femoral neck was correlated with none of them. Serum IGF-I level was significantly and positively correlated with BMD at all sites except the femoral neck (P < 0.01), while serum IGFBP-3 and -4 levels were significantly and positively correlated with only radial BMD (P < 0.01). Serum IGFBP-5 level was positively correlated with UDR BMD (P < 0.001) and negatively correlated with total BMD (P < 0.05). Serum IGF-I, IGFBP-3, and IFGBP-5 levels were significantly lower in women with vertebral fractures than in those without fractures (mean +/- SD: 97.1 +/- 32.1 vs. 143.9 +/- 40.9 ng/dl, P < 0.0001; 2.18 +/- 1.02 vs. 3.23 +/- 1.07 microg/ml, P < 0.0001; 223.6 +/- 63.3 vs. 246.5 +/- 71.5 ng/ml, P = 0.0330, respectively). When multivariate logistic regression analysis was performed with the presence of vertebral fractures as a dependent variable and serum levels of IGF-I and IGFBPs adjusted for age, body weight, height, serum creatinine, and serum alubumin as independent variables, IGF-I and IGFBP-3 were selected as indices affecting the presence of vertebral fractures [odds ratio (OR) = 0.29, 95% confidential interval (CI) 0.15-0.57 per SD increase, P = 0.0003 and OR = 0.31, 95% CI 0.16-0.61 per SD increase, P = 0.0007, respectively]. To compare the significance values, IGF-I, IGFBP-3, and age were simultaneously added as independent variables in the analysis. IGFBP-3 was more strongly associated with the presence of vertebral fractures than IGF-I and age (P = 0.0006, P = 0.0148, and P = 0.0013, respectively). Thus, after comprehensive measurements of serum levels of IGF-I and IGFBPs, it seems that serum IGF-I level is most efficiently associated with bone mass and that serum IGFBP-3 level is most strongly associated with the presence of vertebral fractures in postmenopausal women among the IGF system components examined.

Body composition and vertebral fracture risk in female patients treated with glucocorticoid.

INTRODUCTION: Glucocorticoid (GC) causes bone loss and an increase in bone fragility. However, fracture risk was found to be only partly explained by bone mineral density in GC-treated patients (GC patients). Although GC causes a change in the distribution of fat in the body, the relationship between body composition and fracture risk in GC patients remains unknown. METHODS: The present study examined the relationship between the presence or absence of vertebral fractures and various indices, including body composition, in 92 premenopausal GC patients, 122 postmenopausal GC patients and 122 postmenopausal age-matched control subjects. Dual-energy X-ray absorptiometry was employed to analyze body composition. RESULTS: Percentage lean body mass (LBM), % fat and % trunk fat were not significantly different between postmenopausal GC patients and the control women. When groups with and without vertebral fractures were compared, % LBM and % fat were significantly higher and lower in groups with vertebral fractures, respectively, in postmenopausal GC patients, but not in the postmenopausal control women, although % trunk fat was not significantly different between groups with and without vertebral fractures. Femoral neck BMD was negatively correlated with % LBM and positively correlated with % fat. In premenopausal GC patients, % trunk fat was significantly higher in the fracture group, although % LBM and % fat were not significantly different between groups with and without vertebral fractures. CONCLUSION: The present study revealed that body composition is related to vertebral fracture risk in GC-treated patients. Lower % fat can be included in the determination of vertebral fractures in postmenopausal GC-treated patients. The influence of body composition on vertebral fracture risk may be different between the pre- and postmenopausal state in GC patients.

[Right spontaneous pneumothorax which accompanied absence of right pulmonary artery].

A case had a checkup for dyspnea with a man of 70-year-old, and it was diagnosed as the recurrent right spontaneous pneumothorax. Bulla was found in the right lung with a chest computed tomography (CT), and absence of right pulmonary artery was suspected. Absence of right pulmonary artery was diagnosed by pulmonary arteriography. Re-examination of the patient's chest X-ray from the previous 11 years revealed a chronological decrease of right lung volume and an increase of the cardiothoracic ratio. We performed right bullectomy by thoracoscopic assistance. The postoperative course was uneventful.

Statins modulate the levels of osteoprotegerin/receptor activator of NFkappaB ligand mRNA in mouse bone-cell cultures.

Statins stimulate bone formation partly by inducing osteoblast differentiation, although there is controversy about the effects of statins on bone mineral density and fracture risk. Several studies have revealed that statins suppress bone resorption. However, the mechanism by which statins inhibit bone resorption is still unclear. The present study was performed to clarify the effects of statins on osteoclast formation as well as the levels of osteoprotegerin (OPG) and receptor activator of NFkappaB ligand (RANKL) mRNA in mouse bone-cell cultures by semiquantitative RT-PCR. 10(-8) M 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] significantly stimulated osteoclast formation and 10(-6) M statins (mevastatin and simvastatin) significantly antagonized osteoclast formation stimulated by 1,25(OH)2D3 in mouse bone-cell cultures, including both osteoblasts and osteoclasts. 10(-6) M mevastatin and simvastatin increased the level of OPG mRNA in mouse bone-cell cultures. On the other hand, 10(-6) M mevastatin and simvastatin inhibited the level of RANKL mRNA in these cultures. In conclusion, the present study demonstrates that statins inhibit osteoclast formation in mouse bone-cell cultures. Moreover, statins also increased and decreased the levels of OPG and RANKL mRNA expression in these cultures, respectively. The modulation of OPG/RANKL may be involved in the inhibition of osteoclast formation by statins.

[Castleman disease in the posterior mediastinum showing atypical feature in computed tomography; report of a case].

A 41-year-old man was referred to our hospital because of an abnormal mass on a chest X-ray. An enhanced computed tomography (CT) showed a well-defined round mass (30 x 45 x 66 mm in diameter) that was heterogeneously enhanced owing to central necrotic or cystic change. A 3-dimensional CT demonstrated a couple of feeding arteries to the mass. The mass was completely resected through thoracotomy. Dissection of tight adhesion between the hypervascular mass and the surrounding tissues caused relative amount of hemorrhage during the surgery. The cystic lesion of the mass was fulfilled with brown liquid. The pathological examination revealed the mass as Castleman disease, and scattered cells in the cystic lesion.

The contribution of mast cells to the late-phase of allergic asthma in rats.

INTRODUCTION: Mast cells are thought to be the main cause of an immediate asthmatic response, but their contribution to the late-phase of asthma is unknown. OBJECTIVE: To prove the contribution of preactivated mast cells to the late phase of allergic asthma by advanced activation. METHODS: Mast cell function in the late-phase of asthma was studied. Rats (wild, +/+ and mast cell deficient, Ws/Ws) were challenged with OVA to investigate the relationship between the contraction of airways and the population of inflammatory cells in the trachea. RESULT: During the entire asthmatic period, the contraction of the airway after OVA challenge in +/+ rats was enhanced significantly compared to Ws/Ws rats, especially in the late phase. The bronchoalveolar lavage fluid histamine in +/+, but not Ws/Ws, rats increased 5.3-fold in 30 min and 3.4-fold in 8 h after challenge, significantly. The number of mucosal mast cells in the tracheal epithelial layer in +/+ rats increased significantly 2.2-fold over controls at 8 h after challenge, as demonstrated by in situ hybridization. CONCLUSIONS: Mast cells may contribute to the late phase of asthmatic response by continuous mast cell activation and the mucosal mast cell number increased in the late phase of asthmatic response.

Real-time gesture recognition by learning and selective control of visual interest points.

For the real-time recognition of unspecified gestures by an arbitrary person, a comprehensive framework is presented that addresses two important problems in gesture recognition systems: selective attention and processing frame rate. To address the first problem, we propose the Quadruple Visual Interest Point Strategy. No assumptions are made with regard to scale or rotation of visual features, which are computed from dynamically changing regions of interest in a given image sequence. In this paper, each of the visual features is referred to as a visual interest point, to which a probability density function is assigned, and the selection is carried out. To address the second problem, we developed a selective control method to equip the recognition system with self-load monitoring and controlling functionality. Through evaluation experiments, we show that our approach provides robust recognition with respect to such factors as type of clothing, type of gesture, extent of motion trajectories, and individual differences in motion characteristics. In order to indicate the real-time performance and utility aspects of our approach, a gesture video system is developed that demonstrates full video-rate interaction with displayed image objects.

3D Imaging System for Visualizing and Monitoring Patients.

Three-dimensional (3D) visualization or 3D monitoring of patients or infected animals is useful in actual clinical environment. We propose a 3D imaging system with a single camera and multiple mirrors. The camera is located directly above the object and the multiple mirrors are placed surrounding the object. The single captured image includes multiple viewpoint images: the object captured directly and the same objects reflected by the mirrors. After a simple calibration of the measurement, the 3D volume data are reconstructed with the visual hull based method. Texture mapping is also performed to enhance the reality. A living object was observed in usual environment using this system. The results have demonstrated effectiveness of the system.