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Y Morimoto

Publications and source records attributed to Y Morimoto.

At least 181 records · Page 10Linked to original sources

Extracts of Actinobacillus actinomycetemcomitans induce apoptotic cell death in human osteoblastic MG63 cells.

Whether an extracellular component of periodontal-disease-causing bacteria induces apoptotic cell death in bone-related cells is unknown. To study the effects on osteoblasts of extracts obtained from sonicated Actinobacillus actinomycetemcomitans and Prevotella intermedia, we cultured human osteoblastic cell lines MG63 and Saos-2 cells and mouse osteoblastic cell line MC3T3-E1 cells in the presence of such extracts. The addition of the extracts from Actinobacillus actinomycetemcomitans induced cell death in MG63 cells in a dose- and time-dependent fashion over the concentration range of 0.1 to 10 microg/mL. By contrast, the extracts from Prevotella intermedia did not induce cell death in these cells, even in the presence of 10 microg/mL protein. By using the Hoechst 33342 staining technique, we observed marked nuclear condensation and fragmentation of chromatin in MG63 cells treated with the extracts of Actinobacillus actinomycetemcomitans. DNA ladder formation, a hallmark of apoptosis, also was detected in MG63 cells treated with extracts from Actinobacillus actinomycetemcomitans. In MG63 cells, DNA ladder formation was dose-dependent, with a maximal effect at a concentration of 10 microg/mL, and time-dependent, from 12 to 48 hrs. However, the extracts from Prevotella intermedia did not induce DNA fragmentation in MG63, Saos-2, or MC3T3-E1 cells. The extracts from Actinobacillus actinomycetemcomitans did not induce cell death and DNA fragmentation in Saos-2 and MC3T3-E1 cells. Sonicated extracts of Actinobacillus actinomycetemcomitans that had been treated with heat and trypsin did not induce DNA ladder formation in MG63 cells, suggesting that the apoptosis-inducing factors are proteinaceous. Cycloheximide prevented the Actinobacillus actinomycetemcomitans-induced DNA ladder formation in MG63 cells in a dose-dependent fashion, suggesting that new gene transcription and protein synthesis are regulated for Actinobacillus actinomycetemcomitans-induced apoptosis in MG63 cells. Our results indicate that apoptosis in alveolar bone cells induced by Actinobacillus actinomycetemcomitans plays an important role in periodontal diseases.

3T3 Cells↗

Drug permeation through the three layers of the human nail plate.

The in-vitro permeation characteristics of a water soluble model drug, 5-fluorouracil, and a poorly water soluble model drug, flurbiprofen, were investigated through three layers of the human nail plate (namely, the dorsal, intermediate and ventral nail plates), using a modified side-by-side diffusion cell. The dorsal-filed nail plate, the ventral-filed nail plate and the dorsal-and-ventral-filed nail plate were prepared to known thicknesses and then used with the full-thickness nail plate to investigate the permeation characteristics of each single layer. Most of the lipids in the human nail plate were found in the dorsal and ventral layers. The rank orders of the permeation fluxes for 5-fluorouracil and flurbiprofen were both: dorsal-and-ventral-filed nail plate > dorsal-filed nail plate > ventral-filed nail plate > full-thickness nail plate. With respect to 5-fluorouracil permeation through each single layer, the permeability coefficient of the intermediate layer was higher than those of other single layers. However in the case of flurbiprofen, the permeability coefficient of the ventral layer was higher than other single layers. The diffusion coefficients of 5-fluorouracil and flurbiprofen in the dorsal layer were the lowest of any single layer. The drug concentration in each layer was estimated using each respective permeation parameter. The drug concentration in the nail plate was observed to be dependent on the solubility and the flux of the drug. From these findings, we suggest that the human nail plate behaves like a hydrophilic gel membrane rather than a lipophilic partition membrane and that the upper layer functions as the main nail barrier to drug permeation through its low diffusivity against the drugs.

Diffusion↗

Evaluation of bile acids and fusidate derivative as nasal absorption enhancers using an electrophysiological technique.

The present study was carried out to investigate the reversibility of the action of two nasal absorption enhancers, bile acids and fusidate derivative, on nasal membrane resistance. The nasal mucosa was isolated from rabbit nasal septum and mounted in a Ussing-type chamber to allow the monitoring of the membrane resistance and flux of fluorescein isothiocyanate-labeled dextran (FD10, M.W. 9400). Membrane resistance was reduced by 46% following treatment with 0.5% (w/v) sodium taurodihydrofusidate (STDHF) for 10 min and then gradually returned to the control level after being wash. The resistance was restored to 76% of the control level following a 30 min treatment with 0.5% (w/v) STDHF. However, there was no recovery of resistance following treatment with 0.5% (w/v) STDHF for 120 min or 1% (w/v) STDHF for 10in. Concurrently, FD10 transport was enhanced while membrane resistance was reduced. Treatment with 0.5% (w/v) sodium deoxycholate (DC) for more than 10 min showed no reversible action and marked FD10 transport enhancement, whereas a 10-30 min treatment with 0.5% (w/v) sodium glycocholate (GC) or sodium taurocholate (TC) resulted in the rapid recovery of membrane resistance without any enhancement of FD10 permeation. STDHF transport across the nasal mucosa was approximately 2-fold faster than that of DC, GC, and TC. The accumulation of STDHF in the nasal mucosa was 2-fold lower than that of DC and 1.7-fold higher than that of GC and TC after a 30 min treatment. The rank order of hydrophobicity determined by reverse-phase HPLC was: DC>STDHF>GC>TC. These results suggest that the reduction in membrane resistance and its reversibility appear to be due to a balance between the accumulation and clearance of STDHF.

Absorption↗

Skin disposition of drugs after topical application in hairless rats.

Drug fraction transported from a topical formulation on skin to subcutaneous tissues or muscles is dependent on the physicochemical properties of the entrapped drug. Cutaneous disposition of model drugs, antipyrine (ANP), lidocaine (LC) and piroxicam (PXC) as well as flurbiprofen (FP) was thus evaluated in hairless rats in which an agar gel disc was subcutaneously inserted into the abdominal region as a drug receptor and a drug donor cell was placed above it. Time courses of plasma level and agar gel amount were measured after topical application of 50% ANP, 3% LC, 1% PXC and 1% FP in hydroxypropylcellulose gel. Percutaneous absorption clearance of unionized form, CLab* was proportional to true octanol/water distribution coefficient and the order of FP > PXC > LC > ANP, suggesting that skin permeation of the drug was determined mainly by its distribution from the formulation to the skin barrier. PXC, however, had a relatively low flux compared to the other three drugs, probably due to its high molecular weight and melting point. Migration clearance of unionized form from systemic circulation to the subcutaneous agar gel, CLg* was also influenced by the lipophilicity of drugs. On the other hand, fraction from the formulation to the systemic circulation was in the order of PXC > FP > ANP > LC. This fraction was much higher than the direct migration fraction from the formulation to the subcutaneous agar gel. Factors determining for these fractions are still unclear. A drug having a low lipophilicity and a low protein binding, however, had a tendency to have a great targeting ability to the subcutaneous agar gel. In addition, most of the drug in the agar gel was contributed by the direct flow from formulation, not from the systemic circulation. The present in situ experimental method is a useful tool to evaluate skin disposition of drugs. Detailed understanding of the skin disposition of drugs from several formulations will enable the findings of a good drug and formulation candidates.

Administration, Topical↗

Combined effect of cigarette smoke and mineral fibers on the gene expression of cytokine mRNA.

To investigate which parameters are stimulated by mineral fibers and whether cigarette smoke enhanced a fiber-induced response, we examined the level of cytokine mRNA from alveolar macrophages (AMs) and lungs of rats exposed to mineral fibers and cigarette smoke in vivo. Male Wistar rats were given a single intratracheal instillation of 2 mg of Union Internationale Contre le Cancer chrysotile or refractory ceramic fiber (RF1). The animals then inhaled a side stream of smoke 5 days per week for 4 weeks. The expression of manganese superoxide dismutase, inducible nitric oxide synthase (iNOS), basic fibroblast growth factor (bFGF), interleukin-1[alpha] (IL-1[alpha]), interleukin-6 (IL-6), and tumor necrosis factor-[alpha] (TNF[alpha]) mRNA from lipopolysaccharide-stimulated AMs and lungs of rats exposed to mineral fibers and/or cigarette smoke were assessed using semiquantitative reverse-transcriptase polymerase chain reaction. Exposure only to cigarette smoke increased in IL-1[alpha] mRNA levels in AMs. Chrysotile stimulated the expression of IL-1[alpha], TNF[alpha], and IL-6 in AMs, and the expression of bFGF in lungs. RF1 resulted in increased expression of IL-1[alpha] and TNF[alpha] in AMs. Cigarette smoke stimulated the gene expression of iNOS in AMs and IL-6 and bFGF in lungs treated with chrysotile; IL-1[alpha] in AMs and bFGF in lungs did the same in lungs with RF1. Among these cytokines, message levels of IL-1[alpha], iNOS, and bFGF were increased in rats stimulated with mineral fibers, and the stimulating effects of mineral fibers were enhanced by cigarette smoke. Therefore, IL-1[alpha], iNOS, and bFGF would be the possible parameters of the lung remodeling induced by mineral fibers.

Animals↗

Modulatory effect of a serine protease inhibitor on surgical stress: its clinical implications.

The relationship between endogenous cytokine antagonists and surgical stress is poorly understood. Surgical stress induces immunosuppression, and the reversed therapy of postoperative immunosuppression has been expected. The aim of the present study was to assess the effect of a serine protease inhibitor on postoperative immune reactivity. Twenty patients with colorectal cancer were randomly separated into experimental and control groups of 10 patients each. The experimental group received perioperative administration of a serine protease inhibitor while the control group did not. Plasma levels of cytokine antagonists, which suppress cell-mediated immunity, such as cortisol, interleukin-1 receptor antagonist, soluble interleukin-2 receptor (sIL-2R) and soluble tumor necrosis factors p55, p75 (sTNF-R55, -R75) were simultaneously measured. Significant reductions of plasma concentration of sIL-2R and sTNF-R55 were observed. Perioperative administration of a serine protease inhibitor may contribute to ameliorating immunosuppression after major surgery.

Adult↗

Association between a focal spared area in the fatty liver and intrahepatic efferent blood flow from the gallbladder wall: evaluation with color Doppler sonography.

OBJECTIVE: The purpose of this study was to investigate whether fatty sparing adjacent to the gallbladder fossa is related to efferent blood flow from the gallbladder wall. SUBJECTS AND METHODS: Color and power Doppler sonography were performed in 80 patients with a fatty liver that appeared as a fine echogenic pattern with considerable deep attenuation on sonography. We analyzed whether color signal appeared around the spared area, the gallbladder wall, or both. Subsequently, when such signal was detected, pulse Doppler analysis of the signal was performed. RESULTS: Color signal indicating efferent blood flow from the gallbladder wall was detected in 25 (64%) of 39 patients with a focal spared area at the gallbladder fossa and in two (5%) of 41 patients without a focal spared area. This difference was statistically significant (p < .05). The waveform of efferent blood flow signals (n = 25) that were seen within spared areas was continuous in 23 (92%) of 25 patients and was pulsatile in the remaining two patients (8%). CONCLUSION: Blood flow from the gallbladder wall to areas of the spared liver was frequently revealed by color and power Doppler sonography; therefore, this blood flow may be associated with focal fatty sparing.

Adult↗

A clearance model of inhaled man-made fibers in rat lungs.

A clearance model of inhaled man-made fibers (MMFs) was developed, and the calculated fiber numbers and dimensions were compared with the experimental ones using a glass fiber (GF), ceramic fiber (RF1) and two potassium octatitanate whiskers (PT1, TW). If the translocation rate by macrophages is constant and the effect of dissolution and disintegration can be ignored, the fiber number is expected to decrease exponentially with time. In the experimental study, however, the fiber number did not always decrease exponentially. In the case of RF1, the fiber number decreased almost exponentially and the diameter decreased linearly with the time. The clearance rate constant of GF during 3 to 6 months after the end of one-month exposure was greater than that during 1 to 3 months. On the contrary, the clearance rate constants of PT1 and TW during 1 to 6 months were greater than next six months. The diameter and the length of GF did not change significantly. The fiber length of PT1 tends to become longer with time although the diameter did not change significantly. Our theoretical model gives a satisfactory fit to these experimental results.

Administration, Inhalation↗

Effects of mineral fibers on the gene expression of proinflammatory cytokines and inducible nitric-oxide synthase in alveolar macrophages.

To determine which parameters are useful for the risk assessment of man-made mineral fibers (MMMFs), we examined the gene expression of interleukin-1 alpha (IL-1 alpha), tumor necrosis factor alpha (TNF alpha), interleukin-6 (IL-6) and inducible nitric-oxide synthase (iNOS) in mineral fiber-exposed alveolar macrophages (AMs). Male Wistar rats were intratracheally exposed to saline or mineral fibers suspended in saline (2 mg of crocidolite, chrysotile, alumina silicate refractory fiber (RF1) or potassium octatitanate whisker (TW)). Bronchoalveolar lavage was performed 4 weeks after the fiber-instillation, and the recovered AMs were stimulated by lipopolysaccharide for 2 or 6 hours. Expression of IL-1 alpha, TNF alpha, IL-6 and iNOS from AMs was observed using reverse transcription-polymerase chain reaction (RT-PCR). The levels of IL-1 alpha and IL-6 mRNA induced by mineral fiber exposure were greatest in AMs exposed to TW, crocidolite, chrysotile and RF1 in that order. However, both gene expression of iNOS and TNF alpha were not elevated in both crocidolite and TW exposure, despite their high pathological potential. These data suggested that IL-1 alpha and IL-6 may be useful indicators for the risk assessment of MMMFs.

Administration, Inhalation↗

[Pulmonary tumor mass aberration into the bronchus of the intact right lung during total left lung resection].

A 77-year-old male with lung cancer underwent a total left lung resection. During surgery, there was no ventilatory trouble such as hypoventilation or hypoxia. However, a mass was found in the right main bronchus by endobronchial fiberscopy before extubation. Because the mass could not be aspirated through the endobronchial fiberscope, we extracted it using basket-foreceps. We speculated that surgical procedures may have caused the tumor mass to move to the bronchus of the contralateral intact lung. Accordingly, fiberscopic examination of the airway before extubation should be mandatory, even if there is no ventilatory trouble during lung resection.

Aged↗

[The anesthetic management of a patient with a congenital mediastinal cyst undergoing video-assisted thoracoscopic surgery (VATS)].

We recently conducted video-assisted thoracoscopic surgery (VATS) on an 8-day-old boy in whom a congenital mediastinal cyst had caused obstruction of the left main bronchus. After the surgery, the cyst recurred and caused reobstruction of the airway. When he was 51-day-old, we conducted VATS again. We could not perform cystectomy by VATS because the left lung was inflated, and we conducted cystectomy by thoracotomy.

Airway Obstruction↗

Application of low-intensity ultraviolet irradiation to the treatment for pharmacological vasoconstriction via a percutaneous transluminal approach.

We applied low-power ultraviolet (UV) laser irradiation via a thin flexible optical fiber to an in vivo model of vasospasm using an intravascular transluminal approach. The surgically exposed left femoral arteries of a rabbit were constricted by norepinephrine. A quartz fiber of 400 microm in diameter was introduced into the artery via the right common carotid artery through a 2.5F catheter. The femoral artery lumen was then irradiated with a helium-cadmium laser (wavelength 325 nm, output power 8 mW) through the fiber for 30 s. The UV irradiation increased the mean luminal diameter by 85% in comparison to the precontracted state, while the increase was only 45% in a sham operation. A histopathologic examination revealed no thermal damage and an intact internal elastic lamina. These results suggest that intravascular transluminal irradiation with a low-power UV laser may thus have potentially clinical applications to reverse acute arterial vasospasm.

Angiography↗

Involvement of apoptosis in activation-induced cell death of bacteria-reactive human CD45RO+ T cells.

Although the identity of the T cells that protect against bacteria in humans remains unknown, it is clear that patients with bacterial infection have reduced numbers of T cells in their blood. Here we have determined whether this T cell loss is a consequence of bacterial antigen-mediated activation-induced cell death (AICD). By flowcytometric analysis, less than 0.3% of freshly isolated T cells from healthy volunteers and patients with severe pneumonia were identified as apoptotic. However, during culture the rate of apoptosis in peripheral blood T cells from patients was 3.0 +/- 0.9%; and increased further in the presence of anti-CD3 (7.4 +/- 2.1%) and decreased when IL-2 was added (4.4 +/- 1.3%). In contrast, no changes were observed in healthy volunteers on addition of anti-CD3. Further, anti-CD3 significantly increased the susceptibility to apoptosis of CD45RO+ T cells, but not CD45RA+ T cells from patients, and the percentage of CD45RO+ T cells in patients was significantly higher than that in healthy volunteers. Flowcytometric analysis revealed the expression level of Fas to be higher in the patients than healthy volunteers. Collectively, these findings demonstrated that bacteria-reactive T cells were more susceptible to AICD and that Fas-FasL pathways of apoptosis were involved. AICD of CD45RO+ T cells, therefore, provides an explanation for the loss of bacteria-reactive T cells during bacterial infection.

Adult↗

[Postoperative sore throat and intracuff pressure: comparison among endotracheal intubation, laryngeal mask airway and cuffed oropharyngeal airway].

We studied which device is most useful to reduce postoperative sore-throat. We investigated the relationship between intracuff pressure and postoperative sore-throat in using endotracheal intubation (ET), the laryngeal mask airway (LMA) and the cuffed oropharyngeal airway (COPA) in adult patients. We classified sore-throat into categories; pain at rest, hoarseness and dysphasia. We evaluated pain at rest by the score (0: no pain, 1: mild discomfort, 2: mild pain, 3: severe pain). Pain at rest (scores 1, 2, 3) was complained by 10 patients in ET group, 3 in LMA group, 5 in COPA group on the day of operation, showing significantly lower incidence of pain at rest in LMA group than in ET group. Hoarseness was complained by 15 patients in ET group, 2 in LMA group and 4 in COPA group, showing significantly lower incidence of hoarseness in LMA and COPA groups than in ET group. Dysphasia was complained by 3 in ET group, 1 in LMA group and 2 in COPA group, showing no significant difference. These results suggest that LMA is most appropriate to reduce postoperative sore-throat.

Adult↗

Fas-mediated cytotoxicity by gammadelta T cells during acute rejection in xenotransplantation of spheroidal aggregate-cultured hepatocytes.

Xenogeneic transplantation has recently become a subject of interest for the transplantation community due to the current organ shortage, which could be partially or even totally solved by the development of this strategy. However, xenogenetic rejection remains a formidable barrier preventing such use in a clinical setting. The spheroidal aggregate-cultured hepatocytes of WKA rats were injected into the spleen of C3H mice, and quantitative assessment of transplanted xenogeneic hepatocytes using 99mTc-GSA demonstrated that hepatocytes decreased dramatically 2 days after transplantation (day 2) and few viable hepatocytes in spheroids were detected on day 3. The NK activity significantly increased on day 1, and gammadelta receptor/FasL-expressing T cells appeared on day 2. These results suggested that xenogeneic cytotoxicity consisted of gammadelta T cells through the Fas/Fas ligand system, as well as non-T-cell-mediated cellular response, in the MHC-unrestricted pathway in this intrasplenically transplanted xenogeneic hepatocyte model.

Animals↗

Re-emergence of paragonimiasis in Kyushu, Japan.

During 1986-1998 we found 104 paragonimiasis cases, which were referred to our laboratory for immunodiagnosis or identification of parasite eggs in sputum or bronchoscopic aspirate smears, or in histopathological sections. A majority of patients were middle-aged males. Except for 2 cases of chronic occult infection in an unexpected site, 102 cases were assumed as having active infection. Abnormal findings in chest radiograms were noted over 80% of the patients, though about 20% of them were asymptomatic. Parasite egg detection rates in sputum or bronchoscopic aspirate smears were about 50%. About 80% of patients have eosinophilia and/or elevated serum IgE level. Paragonimiasis is a re-emerging public health issue in Kyushu, Japan.

Adolescent↗