Biomedical subjects

Yoshitaka Okamoto

Publications and source records attributed to Yoshitaka Okamoto.

At least 19 recordsLinked to original sources

PubMed2006

IL-21-induced Bepsilon cell apoptosis mediated by natural killer T cells suppresses IgE responses.

Epidemiological studies have suggested that the recent increase in the incidence and severity of immunoglobulin (Ig)E-mediated allergic disorders is inversely correlated with Mycobacterium bovis bacillus Calmette Guerin (BCG) vaccination; however, the underlying mechanisms remain uncertain. Here, we demonstrate that natural killer T (NKT) cells in mice and humans play a crucial role in the BCG-induced suppression of IgE responses. BCG-activated murine Valpha14 NKT cells, but not conventional CD4 T cells, selectively express high levels of interleukin (IL)-21, which preferentially induces apoptosis in Bepsilon cells. Signaling from the IL-21 receptor increases the formation of a complex between Bcl-2 and the proapoptotic molecule Bcl-2-modifying factor, resulting in Bepsilon cell apoptosis. Similarly, BCG vaccination induces IL-21 expression by human peripheral blood mononuclear cells (PBMCs) in a partially NKT cell-dependent fashion. BCG-activated PBMCs significantly reduce IgE production by human B cells. These findings provide new insight into the therapeutic effect of BCG in allergic diseases.

Adaptor Proteins, Signal Transducing↗

PubMed2006

Study of nasopharyngeal bacterial flora. Second report. Variations in nasopharyngeal bacterial flora in children aged 6 years or younger when administered antimicrobial agents. Part 1.

In our first report, we investigated nasopharyngeal bacterial flora related to penicillin-resistant Streptococcus pneumoniae (PRSP) and beta-lactamase-negative ampicillin-resistant Haemophilus influenzae (BLNAR) and their relation to acute upper respiratory tract infection (AURTI). This report analyzes the results of a study of nasopharyngeal bacterial flora before the administration of antimicrobial agents in 172 AURTI patients aged 6 years or younger. In addition to Gram staining, microscopic observation, and culturing, a polymerase chain reaction (PCR) method was used to identify PRSP (gPRSP) and BLNAR (gBLNAR) drug-resistant genes. Of the patients analyzed, 90% had acute otitis media (AOM) and were aged 2 years or younger. The antimicrobial agents administered were amoxicillin (34%), clavulanic acid/amoxicillin (11%), cefditren pivoxil (CDTR-PI) (43%), and others (12%). This was particularly true for patients administered CDTR-PI, among whom there were many who had already suffered one or more episodes of AOM by the age of 1 year or younger, and many in which gPRSP were detected (P < 0.01). There was a significant relation between the degree of nasopharyngeal inflammation indicated by leukocyte infiltration images and the amount of S. pneumoniae and H. influenzae detected, which are the main pathogenic bacteria causing AOM (P < 0.01). In addition to leukocyte infiltration images, there were cases in which shedding of ciliated cells was observed and/or giant monocytic cells. Both nasopharyngeal leukocyte infiltration images and/or shed cell findings observed in infant AURTI cases are important indices for the prompt detection of gPRSP and/or gBLNAR and appropriate doses of antimicrobial agents.

Age Factors↗

PubMed2006

Study of nasopharyngeal bacterial flora. Second report. Variations in nasopharyngeal bacterial flora in children aged 6 years or younger when administered antimicrobial agents. Part 2.

This report focuses on changes in the nasopharyngeal bacterial flora before and after administration of antimicrobial agents in 172 cases of acute upper respiratory infection in patients aged 6 years or younger. The antimicrobial agents administered were amoxicillin (AMPC) (34%), clavulanic acid/amoxicillin compound (11%), cefditren pivoxil (CDTR-PI) (43%), and others (12%). Changes in nasopharyngeal bacterial flora were investigated with reexaminations conducted after 2-5 days (day 2-5 subgroup), 6-10 days (day 6-10 subgroup), and 11 days and thereafter. There was a significant reduction in the Streptococcus pneumoniae detected in the group administered AMPC (AMPC group) in the day 2-5 subgroup and the day 6-10 subgroup. There was also a significant decrease in H. influenzae in the group administered CDTR-PI (CDTR-PI group) in the day 2-5 subgroup. From this it was inferred that for the most part significant changes in infectious nasopharyngeal bacteria occurred in the day 2-5 subgroups. However, a significant improvement in the degree of inflammation, as indicated by leukocyte infiltration images for the AMPC group, was observed in the day 2-5 subgroup, and for the CDTR-PI group in the day 6-10 subgroup. On the other hand, in both the antimicrobial agent groups, S. pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis were newly detected at reexamination. Furthermore, a difference in the incidence of these bacteria was observed between the 2 antimicrobial agent groups. It was suggested that such phenomena related to the survival of resistant strains or a recurrence otitis media.

Anti-Infective Agents↗

PubMed2006

A phase I study of in vitro expanded natural killer T cells in patients with advanced and recurrent non-small cell lung cancer.

PURPOSE: Human Valpha24 natural killer T (Valpha24 NKT) cells bearing an invariant Valpha24JalphaQ antigen receptor are activated by a glicolipid ligand alpha-galactosylceramide (alphaGalCer; KRN7000) in a CD1d-dependent manner. The human Valpha24 NKT cells activated with alphaGalCer and interleukin-2 have been shown to produce large amounts of cytokines, such as IFN-gamma, and also exerting a potent killing activity against various tumor cell lines. We did a phase I study with autologous activated Valpha24 NKT cell therapy. EXPERIMENTAL DESIGN: Patients with advanced or recurrent non-small cell lung cancer received i.v. injections of activated Valpha24 NKT cells (level 1: 1 x 10(7)/m2 and level 2: 5 x 10(7)/m2) to test the safety, feasibility, and clinical response of this therapeutic strategy. Immunomonitoring was also done in all cases. RESULTS: Six patients were enrolled in this study. No severe adverse events were observed during this study in any patients. After the first and second injection of activated Valpha24 NKT cells, an increased number of peripheral blood Valpha24 NKT cells was observed in two of three cases receiving a level 2 dose of activated Valpha24 NKT cells. The number of IFN-gamma-producing cells in peripheral blood mononuclear cells increased after the administration of activated Valpha24 NKT cells in all three cases receiving the level 2 dose. No patient was found to meet the criteria for either a partial or a complete response. CONCLUSIONS: The clinical trial with activated Valpha24 NKT cell administration was well tolerated and carried out safely with minor adverse events even in patients with advanced diseases.

Adult↗

PubMed2006

Study of upper respiratory tract bacterial flora: first report. Variations in upper respiratory tract bacterial flora in patients with acute upper respiratory tract infection and healthy subjects and variations by subject age.

With the appearance of penicillin-resistant Streptococcus pneumoniae, there has been increasing debate concerning antimicrobial treatments for acute upper respiratory tract infection (AURTI) and acute otitis media in children. This study compares the nasopharyngeal bacterial flora in patients with AURTI (AURTI group; 710 subjects) and healthy subjects (HS group; 380 subjects). The comparisons were made between subjects aged 6 years or younger (0-6 subgroup: 330 subjects), between 7 and 74 years (7-74 subgroup: 668 subjects), and 75 years and older (92 subjects), because the subjects were subgrouped as described above dependent on the maturity of the protective immunity. In the HS group 7-74 subgroup, viridans group streptococci, Staphylococcus aureus, coagulase-negative staphylococci, and Corynebacterium sp. with a detection rate of 10% or more were classified as normal nasal flora (NNF), and Streptococcus pyogenes, Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis were classified as drum cavity pathogens (DCP). In the 0-6 subgroup, although the detection rate for DCP bacteria in the AURTI group tended to be high, it did not reach a significant difference, whereas the detection rate for NNF bacteria was significantly lower. This trend was also observed to some degree in the other age subgroup. In the 0-6 subgroup, leukocyte infiltration observed with a microscope indicated the closest relationship between S. pneumoniae detection rate and detection quantity. These results suggest that in the 0-6 subgroup the tendency for patients with AURTI to have NNF bacteria as well as DCP bacteria should be taken into consideration.

Acute Disease↗

PubMed2006

[Trial of isolation of sick house syndrome and unclassified multiple chemical sensitivities--Definition of sick house syndrome, and symptoms].

PURPOSE: This study was designed to clarify the definition of sick house syndrome (SHS). METHODS: SHS was defined based on the disease related to habitation as follows. 1. The cause of the onset of a disease relates to house. 2. Symptoms appear within house. 3. Symptoms will be less serious or disappear if patient away from house. 4. If patient goes into house, symptoms will appear repeatedly. When it corresponded to all above, it was defined to SHS, and it classified as MCS (multiple chemical sensitivities) without above conditions. Even if SHS is isolated from similar disease completely, characteristic symptoms of MCS are hard to be detected because MCS are combination of two or more diseases. Based on this working hypothesis, the logistic regression by setting MCS as reference was performed so that characteristic symptoms of SHS show odds ratios with exceeding one. RESULTS: The odds ratios with more than two of characteristic symptoms in SHS were "nausea or vomiting" "Troublesome in everything" and the causative substances to which symptoms get worse was "The smell of a perfume and cosmetics". Characteristic symptoms of an allergy disease were detected by comparison with the allergic conjunctivitis, allergic rhinitis, and bronchial asthma, respectively. CONCLUSION: These results showed that the classification method was appropriate. This definition is not fundamentally differed from the definition of the sick-building syndrome of WHO.

Air Pollution, Indoor↗

PubMed2005

Preoperative chemotherapy and radiation therapy for squamous cell carcinoma of the maxillary sinus.

OBJECTIVE: This study was undertaken to assess the prognostic factors for the management of squamous cell carcinoma (SCC) of the maxillary sinus, who received preoperative chemotherapy and radiation therapy (RT). We also elucidated the appropriate sequence of chemotherapy. METHODS: A total of 124 patients (median age 62 years) with SCC of the maxillary sinus were analysed retrospectively. T3 or T4 disease was found in 93% of the patients. Thirty-nine patients received neoadjuvant chemotherapy (NA), 38 patients received concurrent chemoradiotherapy (CRT) and 47 patients received NA followed by CRT. The median dose of RT was 60 Gy. Maxillectomy was undertaken in 98 patients. RESULTS: The 5 year overall survival (OAS) and local control probability (LCP) were 56.6 and 73.7%, respectively. On univariate analysis, surgery (P < 0.0001) and T classification (P < 0.04) were significant prognostic factors for OAS and LCP. Histological grade and nodal status were also related to OAS. However, any chemotherapy sequence was not associated with the treatment outcome. On multivariate analysis, surgery (P < 0.0005) and T classification (P < 0.05) were identified as significant prognostic factors for LCP and OAS. CONCLUSIONS: This study suggests that both surgery and T stage are important prognostic factors for LCP and OAS in the management of SCC of the maxillary sinus. The appropriate sequence of chemotherapy remains to be elucidated in the future study.

Adult↗

PubMed2005

Dendritic cell maturation by CD11c- T cells and Valpha24+ natural killer T-cell activation by alpha-galactosylceramide.

Human invariant Valpha24+ natural killer T (NKT) cells display potent antitumor activity upon stimulation. Activation of endogenous Valpha24+ NKT cells would be one strategy for the treatment of cancer patients. For example, dendritic cells (DCs) loaded with a glycolipid NKT cell ligand, alpha-galactosylceramide (alphaGalCer, KRN7000), are a possible tool for the activation and expansion of functional Valpha24+ NKT cells in vivo. In this report, we demonstrate that the levels of expansion and the ability to produce IFN-gamma of Valpha24+ NKT cells induced by alphaGalCer-loaded whole PBMCs cultured with IL-2 and GM-CSF (IL-2/GM-CSF-cultured PBMCs) were superior to those of cells induced by monocyte-derived CD11c+ DCs (moDCs) developed with IL-4 and GM-CSF. Interestingly, CD11c+ cells in the IL-2/GM-CSF-cultured PBMCs showed a mature phenotype without further stimulation and exerted potent stimulatory activity on Valpha24+ NKT cells to enable them to produce IFN-gamma preferentially at an extent equivalent to mature moDCs induced by stimulation with LPS or a cytokine cocktail. Cocultivation with CD11c- cells in the IL-2/GM-CSF-cultured PBMCs induced maturation of moDCs. In particular, CD11c-CD3+ T cells appeared to play important roles in DC maturation. In addition, TNF-alpha was preferentially produced by CD11c-CD3+ T cells in IL-2/GM-CSF-cultured PBMCs and was involved in the maturation of moDCs. Thus, the maturation of DCs induced by CD11c- T cells through TNF-alpha production appears to result in the efficient expansion and activation of Valpha24+ NKT cells to produce IFN-gamma preferentially.

Antigens, CD↗

PubMed2005

Bcl6 regulates Th2 type cytokine productions by mast cells activated by FcepsilonRI/IgE cross-linking.

Bcl6-deficient (Bcl6-/-) mice displayed Th2 type inflammation, which caused by abnormality of non-lymphoid cells. However, initiators for the Th2 type inflammation were not clear. In order to elucidate the initiators, we investigated property and function of mast cells derived from Bcl6-/- mice. Mast cells were developed from bone marrow cells cultured with IL-3 (BMMCs). Although the development of BMMCs from Bcl6-/- mice was similar to that from wild-type mice, proliferation of Bcl6-/- BMMCs stimulated with IL-3 was slightly lower than that of wild-type BMMCs. When these BMMCs were stimulated by FcepsilonRI/IgE cross-linking, Bcl6-/- BMMCs produced Th2 cytokines more than wild-type BMMCs did. Thus, Bcl6-/- mast cells are one of the initiators for Th2 type inflammation in Bcl6-/- mice, and Bcl6 may be a molecular target for Th2 type allergic diseases.

Animals↗

PubMed2005

Weekly cisplatin administration concurrent with radiation therapy for locoregionally advanced nasopharyngeal carcinoma.

Radiation therapy (RT) with concurrent and adjuvant chemotherapy has been a widely accepted treatment for patients with locoregionally advanced nasopharyngeal carcinoma (NPC). We administered 40 mg/m2 cisplatin (CDDP) weekly, concurrently with RT, to six consecutive patients with locoregionally advanced NPC to evaluate its toxicity and efficacy. The median number of courses of CDDP administration was 4.5 and the median radiation dose was 69.7 Gy. Grade 3 leukopenia was observed in three patients. All but one patient experienced grade 3 or 4 skin reactions, pharyngitis, or dysphagia. All but one patient achieved a complete response, and the remaining patient received radical neck dissection for persistent cervical lymphadenopathies, which contained no cancer cells. All six patients were disease-free at last contact, with a median follow up of 23.5 months. This regimen is well tolerated in patients with locoregionally advanced NPC.

Adult↗

PubMed2005

Expression of membrane-bound CD23 in nasal mucosal B cells from patients with perennial allergic rhinitis.

BACKGROUND: CD23 is the low-affinity receptor for IgE on B cells and is thought to play an important role in regulation of IgE production. OBJECTIVE: To measure the expression of membrane-bound CD23 in nasal B cells and examine its correlation with CD4 subtypes or serum IgE levels in patients with perennial allergic rhinitis. METHOD: We used flow cytometric analysis with double, direct immunofluorescence staining of the mucosal-infiltrating lymphocytes to examine the expression of CD23 in nasal mucosal B cells of patients with perennial allergic rhinitis. The expression of CD23 in nasal B cells of patients with nonatopic rhinosinusitis served as a control. RESULT: The ratio of CD23+ B cells to total B cells in patients with perennial allergic rhinitis was significantly higher than in nonatopic controls, whereas that of B cells to total lymphocytes was unchanged. The ratio of CCR4+ CD4 cells to total CD4 cells in allergic patients was significantly higher than in nonatopic controls, whereas the ratio of CXCR3+ CD4 cells to total CD4 cells was unchanged. There was no significant correlation between the percentages of CD23+ B cells and CCR4+ CD4 cells. In addition, the percentage of CD23+ B cells did not correlate with the total IgE level or with the specific IgE level. CONCLUSIONS: Our results indicate that nasal mucosal CD23-bearing B cells, as well as T(H)2 cells, increase in patients with perennial allergic rhinitis. However, the expression of CD23 did not directly correlate with the number of T(H)2 cells in the nasal mucosa.

Adult↗

PubMed2005

Carotid artery resection: preoperative temporary occlusion is not always an accurate predictor of collateral blood flow.

CONCLUSION: The morbidity predicted by means of preoperative PET studies does not always correlate with the morbidity experienced after permanent carotid artery occlusion. A pre-resection extracranial-intracranial bypass may be necessary to reduce the risk of neurologic morbidity, in particular when carotid artery resection is planned for tumors involving the skull base. OBJECTIVES: Carotid artery resection is generally considered the only curative treatment for patients with advanced head and neck carcinoma involving the carotid artery. PET can be used during temporary occlusion of the internal carotid artery to assess the safety of the procedure. The aims of this paper were to clarify the risk of carotid artery resection and the benefit of extracranial-intracranial bypass. MATERIAL AND METHODS: Twelve patients diagnosed with head and neck cancer adherent to the carotid artery and in proximity to the skull base who had shown good hemispheric collateral blood flow by means of PET underwent carotid artery resection without preoperative bypass. RESULTS: Of the 12 patients who underwent carotid artery resection without reconstruction, 10 suffered no serious neurologic complications; however, 2 suffered cerebral infarctions intraoperatively.

Adenocarcinoma↗

PubMed2005

Suppression of inflammation by dexamethasone prolongs adenoviral vector-mediated transgene expression in murine nasal mucosa.

CONCLUSION: The results of this study demonstrate that suppression of inflammation by dexamethasone attenuates the host immune response against adenoviral-mediated gene transfection and thereby prolongs transgene expression in murine nasal mucosa. OBJECTIVES: Gene transfer using a recombinant adenovirus is a good tool for research and clinical applications, but the immune response to adenoviral vectors can induce inflammation and loss of transgene expression in transfected tissues. In this study we investigated the effects of dexamethasone-induced immunosuppression on adenovirus gene transfer in the nasal mucosa of the mouse. MATERIAL AND METHODS: We administered the recombinant adenovirus Ax1CAlacZ, which encodes Escherichia coli beta-galactosidase (lacZ gene), to the nasal mucosa of mice treated with or without i.p. dexamethasone and evaluated the expression of the lacZ gene on Days 2, 4, 7, 14 and 28. The nasal mucosa was dissected out, and the mRNA level was measured using a LightCycler. The expression of the exogenous beta-galactosidase was detected by means of histochemistry. RESULTS: Dexamethasone treatment significantly increased the mRNA level compared with that in the controls at Days 4, 7 and 14. Histochemistry showed that the expression of beta-galactosidase protein persisted in the dexamethasone-treated mice at Days 7 and 14 but had diminished almost to nothing in the control group.

Adenoviridae↗

PubMed2005

Hyperfractionated radiation therapy for locoregionally advanced nasopharyngeal cancer.

OBJECTIVE: The purpose of this study is to clarify the efficacy and toxicity of hyperfractionated radiation therapy (RT) for patients with nasopharyngeal cancer (NPC). METHODS: Twenty-two patients with NPC treated at our hospital between April 1994 and December 2002 were the subjects of this study. They received hyperfractionated RT with a fraction size of 1.2 Gy, with a median tumor dose of 72 Gy (range 64.8-80.4). During this study period, our institutional strategy for locoregionally advanced NPC included neoadjuvant or concurrent chemotherapy combined with hyperfractionated RT, and 17 patients received some forms of cisplatin-containing chemotherapy. RESULTS: With a median follow-up of 59 months, the estimated 5-year disease-free survival rate and overall survival rate were 72.7 and 85.2%, respectively. Acute hematological toxicities were acceptable and manageable. However, >50% of patients required nutritional support, and experienced severe pharyngitis, skin reaction and body weight loss. With regard to late sequelae, one patient developed grade 3 osteomyelitis, and one patient each developed grade 4 passage disturbance and laryngeal edema. No patients experienced any grades of optic nerve injury or temporal lobe necrosis. CONCLUSIONS: Hyperfractionated RT using 1.2 Gy per fraction, for a total dose of 72 Gy, produces a comparable treatment outcome. Although deleterious neurological sequelae were not observed in this study, caution should be exercised regarding other late sequelae, such as osteomyelitis and passage disturbance.

Adult↗

PubMed2005

Diagnostic value of FDG PET and salivary gland scintigraphy for parotid tumors.

PURPOSE: The purpose of this study was to examine the diagnostic value of the combination of F-18 fluorodeoxyglucose (FDG) PET and Tc-99m pertechnetate salivary gland scintigraphy in parotid tumors. MATERIALS AND METHODS: Seventy-two patients with benign parotid gland tumors (n = 52), malignant parotid tumors (n = 12), and inflammation (n = 8) underwent both FDG PET and salivary gland scintigraphy within 1 week, and 66 of the patients also underwent gallium scintigraphy. All patients were negative on their first fine-needle aspiration (FNA). RESULTS: Malignant parotid tumors showed significantly higher FDG uptake (standard uptake values [SUVs]) than both benign tumors and inflammation, except in Warthin's tumor (5.82 +/- 3.95 vs. 2.07 +/- 1.33; P <0.01). Although the SUV values of Warthin's tumor and malignant parotid tumors overlapped somewhat, Warthin's tumor did demonstrate increased radiotracer uptake, and it was reliably distinguished from other parotid gland tumors by the use of salivary gland scintigraphy. Considering a SUV value >3 as being positive for malignancy and excluding Warthin's tumor on the basis of salivary gland scintigraphy, sensitivity and specificity of FDG PET were 75% and 80%, respectively. These results were superior to those of gallium scintigraphy (58% and 72%, respectively). CONCLUSIONS: Although the diagnostic value of FDG PET in the differentiation of malignant from benign parotid gland tumors was limited because of the high FDG uptake in some benign tumors, and particularly pleomorphic adenomas, combining salivary gland scintigraphy with FDG PET may help to negate this drawback, and this combination may be a more promising approach for differentiation of various parotid gland tumors in patients compared with nondiagnostic needle aspiration.

Adolescent↗

PubMed2005

[Allergic rhinitis].

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Antibodies, Monoclonal↗

PubMed2004

Effects of adenoviral vector-mediated BDNF expression on the bulbectomy-induced apoptosis of olfactory receptor neurons.

The expression of adenoviral vector (Ad)-mediated lacZ and brain-derived neurotrophic factor (BDNF) in mouse olfactory epithelium (OE) was examined, and the effect of BDNF on the survival of the bulbectomized OE was evaluated. A recombinant adenovirus, Ax1CAlacZ, was administrated into the mouse OE after bulbectomy, and the expression of a transferred E. coli beta-galactosidase (beta-gal) gene was confirmed by X-gal staining. The expression and effects of exogenous BDNF in the OE after bulbectomy were examined using immunohistochemistry and the TUNEL method. The adenoviral vector-mediated expression of beta-gal in the mouse OE was detectable for up to 14 days after bulbectomy in vivo. The Ad-mediated expression of BDNF was also observed in the OE after bulbectomy. Exogenously induced BDNF suppressed the degenerative changes of bulbectomized OE. TUNEL staining indicated that the exogenous BDNF enhanced the survival of the bulbectomized OE by inhibiting apoptosis. Ad-mediated expression of BDNF in the mouse nasal mucosa alleviated degenerative changes in bulbectomized OE. Ad-mediated transfer of neurotrophic factors might be applicable in the treatment of olfactory disorders.

Adenoviridae↗

PubMed2004

Sphingosine 1-phosphate inhibits migration of RBL-2H3 cells via S1P2: cross-talk between platelets and mast cells.

To analyze the involvement in allergic reactions of platelets and sphingosine 1-phosphate (Sph-1-P), a lysophospholipid mediator released from activated platelets, the effects of Sph-1-P and a supernatant prepared from activated platelets on mast cell line RBL-2H3 were examined. Sph-1-P strongly inhibited the migration of both non-stimulated and fibronectin-stimulated RBL-2H3 cells, which was reversed by JTE-013, a specific antagonist of G protein-coupled Sph-1-P receptor S1P(2); S1P(2) was confirmed to be expressed in these cells. A similar anti-motility effect of Sph-1-P was observed in a phagokinetic assay. Consistent with these results, treatment of RBL-2H3 cells with Sph-1-P resulted in a rounded cell morphology, which was blocked by JTE-013. Under the present conditions, Sph-1-P failed to induce intracellular Ca(2+) mobilization or histamine degranulation, responses postulated to be elicited by intracellular Sph-1-P. Importantly, the Sph-1-P effect, i.e., the regulation of RBL-2H3 cell motility, was mimicked by the supernatant (both with and without boiling) prepared from activated platelets, and this effect of the supernatant was also blocked by JTE-013. Our results suggest that the motility of mast cells can be regulated by Sph-1-P and also platelets (which release Sph-1-P), via cell surface receptor S1P(2) (not through intracellular Sph-1-P actions, postulated previously in the same cells).

Animals↗