Biomedical subjects

Hisashi Hattori

Publications and source records attributed to Hisashi Hattori.

14 recordsLinked to original sources

PubMed2006

Perioperative respiratory complications caused by cystic lung malformation in Proteus syndrome.

A 7-year-old girl with Proteus syndrome, complicated with severe kyphoscoliosis and cystic lung malformation, developed respiratory complications during and after posterior spinal fusion under general anesthesia. We speculated that low oxygenation while in the prone position contributed to ventilation perfusion mismatch owing to the cystic lung malformation that existed predominantly in the right lung, and that postoperative respiratory failure was caused by initially increased bronchial mucous secretions and secondary persistent bacterial pneumonia. Cystic lung malformation rather than reduced respiratory function, although both can be a cause of mucous clearance impairment, should be considered as one of the predictive factors for perioperative respiratory failure in Proteus syndrome.

Child↗

PubMed2006

TH1/TH2 and regulatory cytokines in adults with otitis media with effusion.

OBJECTIVE: Otitis media with effusion is one of the most common and intractable ear diseases. However, the role of Th1, Th2, and immunoregulatory cytokines on the pathogenesis of the disease in adult patients remains to be determined. The aim of this study is to disclose the cytokine expression in middle ear effusions (MEEs) in adults and to compare the profile on the basis of the presence of allergic rhinitis and the type of effusions. STUDY DESIGN: A prospective controlled clinical study. PATIENTS: MEEs were collected from 80 adult subjects. The concentration of interleukin (IL)-2, IL-4, IL-5, IL-10, IL-12, and interferon (IFN)-gamma in MEEs were determined by using enzyme-linked immunosorbent assay. RESULTS: IL-2, IL-4, IL-5, IL-10, IL-12, and IFN-gamma in MEEs were detected in 60 (75.0%), 33 (41.3%), 42 (52.5%), 14 (17.5%), 80 (100%), and 66 (82.5%) samples, respectively. Among these cytokines, only the concentration of IL-4 in the allergic rhinitis-positive group was significantly higher than that in the allergic rhinitis-negative group. On the other hand, IL-2, IL-12, and IFN-gamma were detected, regardless of the presence of allergic rhinitis, and the concentration of these cytokines correlated with each other. The correlation between the concentration of IL-4 and IL-5 was also detected. In addition, both the incidence rate and the concentration of IL-10 in MEEs were significantly higher in the mucoid type compared with those in the serous type effusions. CONCLUSION: Regardless of allergic status, IL-12 may play a critical role in the pathogenesis of otitis media with effusion by affecting the production of IL-2 and IFN-gamma. In addition, IL-4 may have some impact on the immunologic condition in adults with allergic rhinitis. IL-10 potentially affects the viscosity of MEEs.

Adult↗

PubMed2006

E prostanoid 2 (EP2)/EP4-mediated suppression of antigen-specific human T-cell responses by prostaglandin E2.

Prostaglandin E2 (PGE2) is a lipid mediator that displays important immunomodulatory properties, such as polarization of cytokine production by T cells. Recent investigations have revealed that the effect of PGE2 on cytokine production is greatly influenced by external stimuli; however, it is unclear whether PGE2 plays a significant role in major histocompatibility complex-mediated antigen-specific T-cell responses via binding to one of four subtypes of E prostanoid (EP) receptor alone or in combination. In the present study, we sought to determine the effect of PGE2 on antigen-specific CD4+ T-cell responses in humans, especially in terms of receptor specificity. We used purified protein derivative (PPD) and Cry j 1 as T helper type 1 (Th1) and Th2-inducing antigens, respectively. We generated several different Cry j 1- and PPD-specific T-cell lines (TCLs). PGE2 significantly and dose-dependently inhibited the proliferation and subsequent production of interleukin-4 by Cry j 1-specific TCLs and of interferon-gamma by PPD-specific TCLs upon antigen stimulation. Administration of EP2 receptor agonist and EP4 receptor agonist suppressed these responses in an adenylate cyclase-dependent manner, while EP1 and EP3 receptor agonists did not. Messenger RNA for EP2, EP3 and EP4, but not EP1, receptors were detected in Cry j 1- and PPD-specific TCLs, and no differences in EP receptor expression were observed between them. Furthermore, PGE2 and EP2 receptor agonist significantly inhibited interleukin-5 and interferon-gamma production by peripheral blood mononuclear cells in response to Cry j 1 and PPD stimulation, respectively. These results suggest that PGE2 suppresses both Th1- and Th2-polarized antigen-specific human T-cell responses via a cAMP-dependent EP2/EP4-mediated pathway.

Adenylyl Cyclase Inhibitors↗

PubMed2005

Ganglioside GD3 promotes cell growth and invasion through p130Cas and paxillin in malignant melanoma cells.

Although ganglioside GD3 levels are highly elevated in malignant melanomas, the role of GD3 in melanomas' malignant properties has not been clearly shown. To investigate this problem, we genetically generated GD3-positive (GD3+) transfectant cells from a GD3-negative (GD3-) mutant line SK-MEL-28-N1 and analyzed the phenotypic changes in the transfected cells. GD3+ cells showed markedly increased cell growth and invasive characteristics. Two bands that underwent stronger tyrosine phosphorylation in GD3+ cell lines than in controls after treatment with FCS were found with molecular masses of 130 and 68 kDa. They were identified as p130Cas and paxillin by sequential immunoprecipitation. Their roles in cell growth and invasion were analyzed with a small interfering RNA (siRNA) approach. Cell growth, as analyzed by BrdUrd uptake, was strongly suppressed in GD3+ cells to near the levels of GD3- cells when treated with siRNA for p130Cas but not when treated with siRNA for paxillin. However, treatment with siRNAs of either p130Cas or paxillin resulted in the marked suppression of the invasive activity of GD3+ cells almost to the levels of control cells. These results suggested that these two molecules function as effectors of GD3-mediated signaling, leading to such malignant properties as rapid cell growth and invasion.

Cell Division↗

PubMed2005

Delayed recovery of vecuronium neuromuscular block in diabetic patients during sevoflurane anesthesia.

PURPOSE: To study recovery from vecuronium-induced neuromuscular block in diabetic patients during total iv or sevoflurane anesthesia. METHODS: 30 diabetic patients were assigned to diabetes mellitus (DM)-total iv anesthesia (TIVA); (n = 15) or DM-sevoflurane (S) groups (n = 15). Thirty healthy patients were divided into control-TIVA (n = 15) or control-S groups (n = 15). In the DM-TIVA or control-TIVA groups and DM-S or control-S groups, anesthesia was maintained with propofol and fentanyl, and nitrous oxide-oxygen-sevoflurane 1.7%, respectively. After receiving vecuronium 0.1 mg.kg(-1)iv, recovery of the train-of-four (TOF) was compared among the four groups. RESULTS: Times to the return of T2, T3, or T4 in the DM-TIVA and DM-S groups were longer than in the control-TIVA and control-S groups (46.9 +/- 13.8 vs 32.2 +/- 10.7 and 32.6 +/- 8.7 min for T2, P < 0.05). T1/control in the DM-S group was less than in the control-TIVA and DM-TIVA groups 50 to 120 and 70 to 120 min after receiving vecuronium, respectively (P < 0.05). T1/control in the control-S group was less than in the control-TIVA group 80 to 120 min after receiving vecuronium (P < 0.05). TOF ratio in the DM-S group was less than in the control-TIVA, DM-TIVA, and control-S groups, 60 to 120, 80 to 120, and 80 to 120 min after receiving vecuronium, respectively (P < 0.05). CONCLUSION: In diabetic patients receiving vecuronium, recovery of T1/control and TOF ratio are delayed during sevoflurane anesthesia, but not in association with total iv anesthesia.

Adult↗

PubMed2005

Visual evaluation of fade in response to facial nerve stimulation at the eyelid.

STUDY OBJECTIVE: The aim of this study is to investigate the probability of visual detection of fade in response to train-of-four (TOF) stimulation, double-burst stimulation3,3 (DBS(3,3)), or DBS(3,2) at the eyelid in comparison to that at the thumb. DESIGN: This is a randomized single-blinded study. SETTING: The study took place at the University hospital. PATIENTS AND MEASUREMENTS: Sixty adult patients underwent general anesthesia. INTERVENTIONS AND MEASUREMENTS: Patients were randomly divided into either the eyelid group (n = 30) or the thumb group (n = 30). In the eyelid group, at the varying degrees of neuromuscular block caused by vecuronium, TOF, DBS(3,3), or DBS(3,2) were given at the temporal branch of the facial nerve, and the probability of visual detection of fade in response to TOF, DBS(3,3), or DBS(3,2) was determined at the eyelid. Similarly, in the thumb group, the probability of visual detection of fade in response to TOF, DBS(3,3), or DBS(3,2) was examined at the thumb. MAIN RESULTS: When the true TOF ratios were 0 to 0.60, the probability of detection of TOF fade in the eyelid group was significantly lower than in the thumb group (P < .05). At the true TOF ratios of 0.31 to 0.70, the probability of visual detection of DBS(3,3) fade in the eyelid group was significantly less than in the thumb group (P < .05). When the true TOF ratios were 0.81 to 1.00, the probability of detection of DBS(3,2) fade in the eyelid group was significantly higher than in the thumb group (P < .05). CONCLUSION: The probability of visual detection of fade in response to TOF or DBS(3,3) is lower at the eyelid than the thumb. In contrast, DBS(3,2) fade tends to be seen more frequently at the eyelid than at the thumb.

Adult↗

PubMed2005

Immunohistochemical study of vascular endothelial growth factor (VEGF) and bone morphogenetic protein-2, -4 (BMP-2, -4) on lengthened rat femurs.

BACKGROUND: With a hypothesis that "angiogenesis occurs before osteogenesis," an experimental study using a rat model was carried out. Histological and immunohistochemical examinations of vascular endothelial growth factor (VEGF) and bone morphogenetic protein-2, -4 (BMP-2, -4) were performed at the margins of bone formation after femoral bone lengthening. MATERIAL AND METHODS: Thirty-five Wistar rats weighing 380-400 g (11-week-old males) were used. An external fixator was applied on the femur, and an osteotomy performed under general anaesthesia. Five days after the operation, femoral lengthening was initiated at a rate of 0.8 mm/day for 8 days. The rats were sacrificed just after distraction was completed, and at 1, 3, 5, 7, 9 and 14 days after distraction. The specimens from these rats were stained with haematoxylin-eosin, VEGF, and BMP-2, -4 immunohistochemical staining, and were investigated. RESULTS: Expression of VEGF was observed in the woven bone at the osteogenetic front and near to osteoblasts around the newly formed bone. On the other hand, expressions of BMP-2, -4 were seen in the hypertrophic chondrocytes. In the same specimen, the VEGF area was further away from the bone stump than the BMP-2, -4 areas. CONCLUSION: These results confirm the hypothesis that angiogenesis is induced before osteogenesis.

Animals↗

PubMed2005

GM1 expression in H-ras-transformed NIH3T3 results in the suppression of cell proliferation inducing the partial transfer of activated H-ras from non-raft to raft fraction.

c-H-ras is located in lipid/rafts and undergoes cholesterol dependent regulation. To analyze the regulatory effects of ganglioside GM1 on the proliferation of fibroblasts transformed with mutated ras gene, GM1 synthase cDNA was transfected into NIH3T3/H-ras cells containing mutation. In the transient expression system with EGFP-fused GM1 synthase, the ratio of BrdU-positive cells among EGFP-positive cells was compared between GM1(+) transfectant cells and control cells, indicating that the transient GM1 expression suppresses cell proliferation. Then, established transfectant cells C21 and C34 expressed definite levels of GM1, and analyzed for the cell growth with the control cells D2 and D4 expressing no GM1. GM1(+) cells showed reduced proliferation compared with controls. Phosphorylation levels of ERK1/2 after FCS treatment were examined, showing that those on the GM1(+) transfectant cells increased slowly, while those in the controls rapidly reached the plateau. Fractionation of Triton X-100 extracts with sucrose density gradient ultra-centrifugation revealed that activated H-ras proteins from controls as well as NIH3T3/H-ras were completely localized in non-GEM/raft fraction. On the other hand, some portions of activated H-ras were transferred to GEM/raft fraction, i.e., 32% in C21, and 8% in C34. Since the Ras effector Raf-1 was localized in non-GEM/raft, the growth suppression might be caused, at least partly, by the movement of activated H-ras to GEM/raft fraction.

Animals↗

PubMed2003

Roles of FcgammaRIIB in nasal eosinophilia and IgE production in murine allergic rhinitis.

The low-affinity IgG Fc receptor, FcgammaRIIB, displays inhibitory potential in experimental models such as autoimmune diseases. However, whether this receptor is involved in the onset of allergic diseases remains unknown. This study examines the role of FcgammaRIIB in the initiation of allergic rhinitis in mice. Repeated intranasal sensitization with Schistosoma mansoni egg antigen (SEA) induced SEA-specific IgE and marked nasal eosinophilia in high-responder BALB/c mice. FcgammaRIIB gene-deficient (-/-) BALB/c mice displayed severe eosinophilia compared with that of wild-type counterparts. However, FcgammaRIIB -/- mice conversely produced less SEA-specific IgE. The production of interleukin (IL)-4 but not of IL-5 or IFN-gamma by nasal mononuclear cells was also decreased in FcgammaRIIB -/- mice, suggesting that the exacerbation of nasal eosinophila in FcgammaRIIB -/- mice is independent of the local IL-5 levels. The findings in low responder C57BL/6 mice were similar. In addition, nasal eosinophilia in FcgammaRIIB -/- mice passively sensitized with SEA was exacerbated, and conversely, specific IgE production was inhibited after a nasal challenge. These results suggest that FcgammaRIIB plays a regulatory role in the initiation of allergic rhinitis that is independent of either mouse strain or type of sensitization.

Animals↗

PubMed2003

Neuromuscular blockade can be assessed accelerographically over the vastus medialis muscle in patients positioned prone.

PURPOSE: To study accelerographic monitoring of neuromuscular blockade over the vastus medialis muscle in anesthetized patients in the prone position. METHODS: Sixty adult patients were divided into four groups of 15: prone (P)-post-tetanic count (PTC), P-train-of-four (TOF), supine (S)-PTC or S-TOF group. In the P-PTC and P-TOF groups, the muscular branch of the femoral nerve was stimulated and the movement of the vastus medialis muscle was measured accelerographically. In the S-PTC and S-TOF groups, the depth of neuromuscular blockade was assessed mechanically at the thumb. After administration of vecuronium 0.1 mg.kg(-1), TOF stimuli were delivered every 20 sec in all groups. Onset of neuromuscular blockade (time from vecuronium to the minimum level of T1 (first response of TOF) was compared between the P-PTC or P-TOF group and S-PTC or S-TOF group. Recoveries of PTC and those of TOF were compared between the P-PTC and S-PTC groups and P-TOF and S-TOF groups, respectively. RESULTS: Onset of neuromuscular blockade in the P-PTC or P-TOF group was shorter than in the S-PTC or S-TOF group (132 +/- 43 vs 233 +/- 40 sec, mean +/- SD, P < 0.001). Recoveries of PTC in the P-PTC and S-PTC groups followed a similar time course. Recoveries of T1/control in the P-TOF and S-TOF groups were also comparable. In contrast, train-of-four ratio (T4/T1, TOFR) in the P-TOF group was higher than in the S-TOF group 60-120 min after vecuronium (P < 0.05). CONCLUSIONS: The degree of neuromuscular blockade can be assessed accelerographically over the vastus medialis muscle even when patients are in the prone position. When evaluated accelerographically over the vastus medialis muscle, onset of neuromuscular blockade is quicker and TOFR is higher than that assessed at the thumb.

Analysis of Variance↗

PubMed2003

Nerve terminals extend into the temporomandibular joint of adjuvant arthritic rats.

The innervation of the temporomandibular joint (TMJ) has attracted particular interest because of the close association with complex mandibular movement. Although the pathological changes of disk innervation may have a crucial role in the development of TMJ pain, the innervation of the TMJ disk by experimentally induced arthritis has rarely been examined in detail. Arthritic rats were induced by injection with 0.1ml solution of Complete Freund's adjuvant (CFA). We investigated three-dimensional distribution of nerve fibers in the TMJ disk using immunohistochemistry for protein gene product-9.5 (PGP-9.5) and calcitonin gene-related peptide (CGRP) in naive and arthritic rats. To clarify the possible role of nerve growth factor (NGF) and its receptor on changes in peripheral innervation of the TMJ, the expressions of trkA and p75 receptor in trigeminal ganglia were examined. Although PGP-9.5 and CGRP immunoreactive (ir) fibers were seen in the peripheral part of the TMJ disk, they were not seen in its central part. The total length and the length density of PGP-9.5 ir and CGRP ir nerve fibers increased in arthritic rats. The innervation area of fibers proliferating in the rostro-medial part merged with that of fibers in the rostro-lateral part in the arthritic rats. In addition, the ratio of trkA- and p75-positive small- and medium-sized cells increased in trigeminal ganglia. It is assumed that increasing innervation of the TMJ disk may be important for the pathophysiology of TMJ pain. NGF and its receptors are likely involved in pathological changes of the TMJ disk.

Animals↗

PubMed2003

Role of macrophage migration inhibitory factor in otitis media with effusion in adults.

Otitis media with effusion (OME) is one of the most common ear diseases. Bacterial endotoxins and several inflammatory cytokines appear to be involved in the pathogenesis of OME in children; however, little is known of the immunological aspects of the onset of OME in adults. We sought to determine the presence of macrophage migration inhibitory factor (MIF) as well as interleukin 1beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha), RANTES (regulated upon activation, normal T-cell expressed and presumably secreted), and endotoxin in middle ear effusions (MEEs) from adult patients with OME. In addition, the levels of MIF in MEEs from adults and children were compared. MEE was obtained from 95 adults and 11 children. The levels of MIF, IL-1beta, TNF-alpha, and RANTES were determined by enzyme-linked immunosorbent assay, and the concentrations of endotoxin and total protein were determined by the Endospec assay and bicinchoninic acid assay, respectively. MIF was detected in 97.9% of the MEEs from adults, while endotoxin, IL-1beta, TNF-alpha, and RANTES were detected in 96.8, 12.6, 5.3, and 43.9%, respectively. In addition, the level of MIF was significantly higher than those of endotoxin, IL-1beta, and TNF-alpha. A positive correlation between the levels of MIF and endotoxin was observed. MIF and endotoxin were detected in 81.8 and 72.7%, respectively, of the MEEs from the children. The level of MIF was significantly higher in the children, and conversely that of endotoxin was significantly higher in the adults. These results suggest that the interaction between MIF and endotoxin may promote fluid collection in the middle ear, particularly in adults.

Adult↗

PubMed2002

[Sonic hedgehog].

We investigated ectopic cartilage and bone formation induced by transplantation of cells which were transfected with Sonic hedgehog (Shh) cDNA encoding amino-terminal peptide for gene therapy in bone regeneration. These results indicated Shh regulated early chondrogenesis and stimulation of prechondrocytes, and consequently the synergistic effects of Shh and BMP induced bone formation in vivo. In the future, further study of transfection of Shh combined with other gene groups regulating bone formation, or other bone-stimulating factors, or using new type of scaffold will be needed to confirm clinical application.

English Abstract↗

PubMedDate not supplied

Signals through CD40 play a critical role in the pathophysiology of Schistosoma mansoni egg antigen--induced allergic rhinitis in mice.

BACKGROUND: Interaction between CD40 and CD40L is thought to regulate immune responses in several allergic diseases. However, little is known about its in vivo role in the pathophysiology of allergic rhinitis. We sought to determine whether the lack of signals through CD40 affects the pathophysiology of allergic rhinitis using a murine model. METHODS: Wild type (WT) and CD40-deficient BALB/c (CD40-/-) mice were sensitized intranasally to Schistosoma mansoni egg antigen (SEA). After repeated sensitization, histamine responsiveness, serum antibody titer including immunoglobulin E (IgE), nasal eosinophilia, and cytokine production by nasal mononuclear cells were determined in each group. RESULTS: Intranasal sensitization with SEA in WT mice elicited a strong Th2 response including SEA-specific IgE production, nasal eosinophilia, and interleukin (IL)-4, and IL-5 production by nasal mononuclear cells after antigen challenge. Production of SEA-specific IgE and IgG1 was abolished in SEA-sensitized CD40-/- mice. These mice showed impaired nasal eosinophilia and displayed markedly reduced histamine-induced nasal hyperresponsiveness as compared with WT mice. Furthermore, reduced production of IL-4 and IL-5 by nasal mononuclear cells was seen in CD40-/- mice. CONCLUSION: These results show that signals through CD40 play a critical role in not only IgE production but also pathophysiology of allergic rhinitis such as nasal hyperresponsiveness and nasal eosinophilia.

Animals↗