The mandible advancement may alter the coordination between breathing and the non-nutritive swallowing reflex.

The coordination between nasal breathing and non-nutritive swallowing serves as a protective reflex against potentially asphyxiating material, i.e. saliva and secretions, entering the respiratory tract. Although this protective reflex is influenced by positional changes in the head and body, the effect of mandible position on this reflex is not fully understood. We examined the effect of mandible advancement associated with mouth opening on the coordination between nasal breathing and non-nutritive swallowing induced by continuous infusion of distilled water into the pharyngeal cavity. The combination of mandible advancement and mouth opening increased the duration of swallowing apnoea and submental electromyographic burst duration. When the mandible was advanced with the mouth open, the duration of swallowing apnoea increased significantly compared with the centric position (0.79 +/- 0.23 vs. 0.64 +/- 0.12 s, P < 0.05, n = 12), and the duration of submental electromyographic activity increased significantly (2.11 +/- 0.63 vs. 1.46 +/- 0.25 s, P < 0.05, n = 12). Mandible advancement with mouth opening altered the respiratory phase resetting during swallowing and the timing of swallow in relation to respiratory cycle phase. We conclude that mandible re-positioning may strongly influence the coordination between nasal breathing and non-nutritive swallowing by altering respiratory parameters and by inhibiting movement of the tongue-jaw complex.

Safety of tooth extraction in patients receiving direct oral anticoagulant treatment versus warfarin: a prospective observation study.

The aim of this study was to compare the safety of tooth extraction in patients receiving direct oral anticoagulants (DOACs) or warfarin without cessation of their antithrombotic treatment. This prospective observational study included 367 patients undergoing tooth extraction (119 receiving DOACs and 248 receiving warfarin). All extractions in DOAC patients were performed 6-7h after taking DOACs in consideration of the half-life in blood under continued antithrombotic treatment. To examine the potential postoperative bleeding risk related to the time of extraction and the drug concentration of blood, activated partial thromboplastin time (APTT) in dabigatran and prothrombin time (PT) in rivaroxaban were measured three times after administration. A total of 390 tooth extractions were performed: 128 in the DOAC patients and 262 in warfarin patients. Postoperative bleeding occurred in four extractions (3.1%) in the DOAC group and in 23 (8.8%) in the warfarin group. There was no statistically significant difference between the two groups (odds ratio: 2.362, 95% confidence interval (CI) 0.819-6.815, p=0.112). APTT and PT prolongation in almost all cases decreased with time after taking the medicine. Our findings suggest that interruption of DOAC therapy is not necessary for tooth extraction if the procedure is performed at least 6h after the last dose.

Securing the coronoid process during a coronoidotomy.

Sagittal application of a titanium mini screw in the coronoid process at the time of coronoidotomy is a very efficient method for easy removal.

A prospective study to evaluate a new dental management protocol before hematopoietic stem cell transplantation.

Pre-hematopoietic stem cell transplantation (HSCT) dental treatment is essential to prevent serious infections from oral sources during immunosuppression, in patients who undergo HSCT therapy. This study was planned to establish a dental management protocol for such patients. Forty-one patients scheduled for HSCT to treat hematological malignancies were consecutively enrolled in the prospective trial. The dental status of all patients was evaluated by clinical and radiographic examination at a median of 47 days before the commencement of HSCT therapy. Thirty-six patients had one or more dental diseases; the remaining five had none. Caries was found in 26 patients, apical periodontitis in 19, marginal periodontitis in 24 and a partially erupted third molar in 11. Our policy is to preserve patients' teeth whenever possible, and therefore minimal dental intervention was planned. Treatment was completed for all 36 patients with dental pathologies, before the conditioning regimen began. All patients received the scheduled HSCT therapy without alteration, interruption or delay, and did not show any signs or symptoms associated with odontogenic infection while they were immunosuppressed. This protocol, therefore, appears to be appropriate for the pre-HSCT dental treatment of patients with hematological diseases.

Steroid-free induction and preemptive antiviral therapy for liver transplant recipients with hepatitis C: a preliminary report from a prospective randomized study.

Recurrence of hepatitis C (HepC) has been a most difficult dilemma in liver transplantation (OLT) because the effects of immunosuppression with steroid, mycophenolate mofetil (MMF) calcineurin antagonists, and anti-interleukin-2 antibody as well as the role of preemptive antiviral therapy are uncertain. In this study, we randomized OLT recipients with HepC into two treatment arms: tacrolimus+daclizumab+MMF (study arm) versus tacrolimus+steroids+MMF (control arm). The study arm only received steroids for the treatment of biopsy-proven rejection episodes. Both arms received preemptive anti-viral therapy with Pegasys and ribavirin. The 39 enrolled patients (among 50 to be enrolled) have median follow-up of 458 days with 23 patients (8 in study arm, 15 in control arm) having reached 1 year. The incidences of rejection episodes within 0 to 3 months, 3 to 6 months, and 6 to 12 months were (study vs control): 0% vs 28%; 0% vs 6%; and 13% vs 20%; respectively (P = NS). The 1-year protocol biopsies showed advanced fibrosis (stage 3 or greater) in 20% (3 of 15) of the control arm, but none (0 of 7) of the study arm (P = NS). We compared anticipated side effects of steroids in the first 3 months (study vs control): hypertension (36% vs 58%, P = NS), PTDM (7% vs 43%, P = .02), and wound infections (14% vs 37%, P = NS). In conclusion, liver transplant recipients with HepC tolerate a steroid-free protocol. There was a trend toward reduced steroid side effects and a lower incidence of advanced fibrosis in 1-year biopsy samples among patients receiving the steroid-free protocol.

Risk factors for postoperative delirium in patients undergoing head and neck cancer surgery.

This study was carried out to determine risk factors for delirium after major head and neck cancer surgery. The postoperative experience of 38 patients who underwent major head and neck cancer surgery and were managed in the high care unit was retrospectively examined by reviewing their medical records. Delirium was defined as confusion and abnormal behavior that interfered with postoperative recovery. Postoperative delirium occurred in 10 patients (26.3%) who all had stage IV cancer, flap reconstruction, an operative time of more than 10 h, blood transfusion of more than 4 units or infusion of more than 5000 ml, which together suggested the risk of delirium increased significantly with extensive surgery. Delirium occurred less frequently in patients with minor tranquilizer use for postoperative sleep disorder. Multivariative analyses showed an operative time of >10 h and no use of minor tranquilizer as significant factors for increasing the incidence of delirium, with odds ratios (95% confidence interval) of 11.4 (1.5-83.8) and 9.8 (1.5-66.0), respectively.

PDGFR alpha expression during mouse embryogenesis: immunolocalization analyzed by whole-mount immunohistostaining using the monoclonal anti-mouse PDGFR alpha antibody APA5.

We investigated the cells that express platelet-derived growth factor receptor alpha (PDGFR alpha) during mouse embryogenesis. PDGFR alpha expression has been identified by in situ hybridization or immunohistochemistry using polyclonal antibodies on tissue sectins. Because no immunostaining study using whole-mount specimens has been published to date, we established a new monoclonal antibody (MAb), APA5, for this purpose. Our results differed in that APA5 stained only the paraxial mesoderm, whereas other investigators concluded that most if not all mesodermal cells expressed PDGFR alpha. Moreover, we did not find PDGFR alpha expression in embryonic erythrocytes, which have been previously suggested to express PDGFR alpha. On the basis of our present results, we wish to revise the proposed PDGFR alpha expression as follows. At the pregastrulation stage, PDGFR alpha is expressed only in primitive endoderm, particularly that in the ectoplacental cone. On gastrulation, it is expressed at high levels in the paraxial mesoderm. This expression continues after its differentiation into the somite. Along with the differentiation and migration of the sclerotome, PDGFR alpha + cells begin to become distributed throughout the embryonal mesenchyme. During organogenesis, particularly intense staining is detected in regions of epithelial and mesenchymal interaction, such as the tooth bud and bronchi. In addition to mesodermal derivatives, the developing lens, apical ectodermal ridge, glial precursor, cardiac valves, and choroid plexus express PDGFR alpha. Our results with whole-mount immunostaining show that PDGFR alpha is abundantly expressed and may play important roles during embryogenesis.

Active-MMP2 in cancer cell nests of oral cancer patients: correlation with lymph node metastasis.

We examined the gelatinolytic activity in human oral squamous-cell carcinoma tissues in order to evaluate the capability of intravasation and extravasation of cancer cells. By a microdissection-zymography, we demonstrated separately the gelatinolytic activities in cancer cell nests and stroma adjacent to the cancer cells. The gelatinolytic activities, such as pro-matrix metalloproteinase (MMP)9 and active-MMP2 in most of cancer cell nests were much higher than those of normal gingival epithelium. Moreover, the activities of active-MMP2 in cancer cell nests of metastatic cancers were significantly higher than those of non-metastatic cancers (p<0.05). These results suggest that active-MMP2 in cancer cells can be a predictive marker for metastasis formation in oral squamous-cell carcinoma patients.

Grafting of encapsulated dopamine-secreting cells in Parkinson's disease: long-term primate study.

The transplantation of encapsulated dopamine-secreting cells into the striatum represents one potential means of treating Parkinson's disease. The present study investigated the ability of encapsulated PC12 cells, which are derived from rat pheochromocytoma, to supply L-dopa and dopamine into the primate brain in the long term and to effect functional improvement in the animals. Following polymer encapsulation, PC12 cells were transplanted into the striatum of hemiparkinsonian monkeys. The secretion of L-dopa and dopamine from the encapsulated cells, the morphology of these cells, the histology of the host striatum surrounding the capsule, and functional changes in the host animals were examined 1, 6, and 12 months after transplantation. Analysis of retrieved capsules revealed that the PC12 cells survived and continued to release L-dopa and dopamine even 12 months after transplantation. The histological response of the host brain surrounding the capsules was minimal and there were no signs of immunological rejection or tumor formation. The physical condition of the host animals was good for 12 months, and hematologic and cerebrospinal fluid analysis revealed that no animals suffered from infection or immunological reaction. These PC12 cell-grafted monkeys showed improvements in hand movements after transplantation, effects that lasted for at least 12 months. These results further support the potential use of this approach for the treatment of Parkinson's disease.

Neurotrophic factor-secreting cell grafting for cerebral ischemia: preliminary report.

In this experiment, we examined a possible protective effect of encapsulated neurotrophic factor-secreting cell grafting for ischemic injury. We established a basic fibroblast growth factor (bFGF)-secreting cell line by genetic manipulation. We enveloped these cells into polymer capsules, which consist of a semipermeable membrane, and implanted them into the right striatum of rats. At 6 days after implantation, these rats received right middle cerebral artery occlusion (MCAO) using interluminal suture technique. At 24 h after MCAO, rats were sacrificed and their cerebral infarction volume was determined by 2,3,5-triphenyltetrazolium chloride (TTC) staining and image analysis. We found approximately 30% reduction in infarct volume in the encapsulated bFGF-secreting cell grafting groups vs. the encapsulated naive BHK cell grafting group or the without implantation group. We measured bFGF secretion from encapsulated bFGF-secreting cells using enzyme-linked immunosorbent assay (ELISA). The retrieved capsules continued to secrete bFGF. There was no significant difference of bFGF secretion between the capsules before and after transplantation. A large number of viable BHK-bFGF cells was observed within the full length of the retrieved capsule. These results indicate that encapsulated bFGF-secreting cell grafting exerts a protective effect on ischemic injury.

Suppression of induction of experimental immune mediated blepharoconjunctivitis by tolerogenic conjugates of the antigen and monomethoxypolyethylene glycol.

AIM: Covalent conjugates consisting of diverse antigens coupled to optimal numbers of monomethoxypolyethylene glycol (mPEG) molecules have been shown to suppress antigen specific antibody formation. In this study, the possibility was examined that the same conjugates might prevent experimental immune mediated blepharoconjunctivitis (EC, formerly EAC) which had been shown to be caused by CD4(+) T cells-that is, to cell mediated immunity. METHODS: 6-8 week old male Lewis rats were used. The test groups of rats received two intravenous injections, each of 300 microg, of a conjugate of ovalbumin mPEG (OVA(mPEG)(11)) in phosphate buffered saline (PBS), 14 and 28 days before the single immunisation with OVA in complete Freund's adjuvant. The rats were challenged 3 weeks later by eye drops containing OVA; 24 hours later they were sacrificed, and their eyes, blood, and lymph nodes were harvested for histological examination and determination of anti-OVA antibody titres and levels of cellular immunity. Two control groups received PBS or OVA in PBS before immunisation. Furthermore, the possibility that OVA(mPEG)(11) may have induced OVA specific suppressor cells was tested by establishing the effects of the co-transfer of splenocytes from OVA(mPEG)(11) treated rats with OVA primed lymph node cells on the manifestations of EC. RESULTS: Either PBS or OVA pretreated rats, which had not received OVA(mPEG)(11), developed high levels of antibodies and cell mediated immune responses to OVA, and application of eye drops led to blepharoconjunctivitis with massive cellular infiltration. In contrast, pretreatment with OVA(mPEG)(11) prevented cellular infiltration into the lids and conjunctivas, as well as the formation of detectable humoral and cellular immunity against OVA. Co-transfer of splenocytes from OVA(mPEG)(11) treated rats with OVA primed lymph node cells suppressed the cellular infiltration on application of OVA on the conjunctiva. CONCLUSIONS: These data indicate that intravenous injection of OVA(mPEG)(11) conjugates suppressed both humoral and cellular immunity by the effects of antigen specific suppressor cells, thus leading to the inhibition of development of EC.

Effects of calcitonin gene-related peptide on the adenylate cyclase system in cultured rat skeletal muscle cells.

Adenylate cyclase (AC) activity in skeletal muscle cells isolated from new born rats was increased with time in culture, indicating the presence of heterologous supersensitivity as in the case of denervation in vivo. The effect of addition of calcitonin gene-related peptide (CGRP) to the cultures of skeletal muscle cells on increase in the AC activity was studied. The increases in AC activity stimulated by CGRP, isoproterenol, NaF and forskolin were depressed by exposure to CGRP (1 microM) for 24 hours, depression of CGRP-stimulated AC activity being the greatest. The extent of reduction in increase in AC activity depended on the concentration of CGRP and duration of exposure. The AC activity stimulated by CGRP was also decreased by exposure to dbc-AMP for 24 hours. When muscle cells were exposed to CGRP for 3 days, no significant difference among the AC activity stimulated by NaF, forskolin and CGRP was seen. These results suggest that exposure to CGRP for one day caused mainly homologous desensitization of the CGRP receptor, whereas exposure for 3-4 days caused heterologous desensitization of the AC catalytic unit, perhaps by elevating the c-AMP level in the cells. These results imply that CGRP, which is located in the motor nerve terminal, may play a role as a physiological trophic factor on skeletal muscle.

Hypochlorite scavenging activity of polyphenols.

Chemiluminescence, generated by the mixture of sodium hypochlorite solution and luminol, was completely eliminated by polyphenols, such as natural lignins, phenylpropenoid monomers and polymers, and epigallocatechin gallate. On the other hand, hypochlorite scavenging activity of polysaccharides, such as PSK (Krestin) and Schizophyllan, was relatively weak. Human myelogenous leukemic cell lines (HL-60, ML-1) showed higher production of active oxygen(s) (detected by luminol chemiluminescence) and iodination capacity, than six other cultured cell lines. Since lignin did not completely eliminate the active oxygen production by HL-60 cells, possible stimulation of hypochlorite production by lignin was suggested.

Pathogenicity of bacteria using a simulated root canal system.

The purpose of this study was to investigate the reliability of an implantation test using Teflon-simulated root canals for evaluating the pathogenicity of root canal bacteria. Models including suspensions of lyophilized strains (Actinomyces israelii, Streptococcus faecalis, and Porphyromonas asaccharolyticus) were implanted in rat subcutaneous tissue for 1 wk, and histological changes were observed. Severe inflammation occurred around the models. Among them, P. asaccharolyticus induced the severest inflammatory response. Further study using P. asaccharolyticus was conducted to compare the implantation test's ability to evaluate pathogenicity with that of an injection test at 1, 2, or 4 wk. Tissue injected with a bacterial suspension showed no clear response through the experimental periods, whereas tissue around implantation sites showed a severe response at 1 wk. However, the inflammatory response subsided at later stages. Consequently, further improvement is needed to investigate pathogenicity for long periods.

Studies on the isothermal crystallization of D-glucose and cellulose oligosaccharides by differential scanning calorimetry.

Isothermal crystallization from the glassy state of D-glucose and cellulose oligosaccharides (e.g., cellobiose, cellotriose, and cellotetraose) has been studied by differential scanning calorimetry. The crystallization of amorphous D-glucose and oligosaccharides was very difficult in the absence of traces of water. Amorphous cellobiose and cellotetraose crystallized far more rapidly than amorphous D-glucose and cellotriose. The activation energy for the crystallization of cellobiose and cellotetraose was approximately 10-12 kJ. mol(-1), while that for D-glucose and cellotriose was approximately 1-2 kJ. mol(-1). An odd-even effect seemed to be associated with the crystallization process of these saccharides.

Longitudinal changes of symptoms of temporomandibular disorders in Japanese young adults.

Longitudinal changes of symptoms of temporomandibular disorders in 275 Japanese university students were investigated through use of questionnaires in 1990 and in 1994. A comparison of the 1990 responses with the 1994 responses revealed that the prevalences of temporomandibular joint sounds, mouth opening restriction, and pain significantly increased from 28.7% to 49.8%, from 12.7% to 22.5%, and from 7.6% to 18.5%, respectively. The increase in the prevalence of symptoms mainly resulted for students who did not have symptoms of temporomandibular disorders at the first examination. Subjects who had been frequently aware of symptoms of temporomandibular disorders showed a tendency toward a decrease in their frequency of awareness. Although 66 students (24.0%) reported discomfort from symptoms of temporomandibular disorders during the period, only three (1.1%) visited medical facilities to receive treatment. These results suggest that symptoms of temporomandibular disorders evaluated through the use of questionnaires are longitudinally fluctuant, and that few students developed temporomandibular disorders.

Screening method for cellulose biosynthesis inhibitors with herbicidal activity.

A new screening method for inhibitors of cellulose biosynthesis is described. This method utilized three microbial strains; a cellulose-containing fungus Phytophthora, and a cellulose non-containing fungus Candida, and a bacterial strain of Acetobacter, a cellulose-producing acetic acid bacterium. The primary screen examined microbial cultures for selective growth inhibition against Phytophthora with no inhibition against Candida. The secondary screen tested for herbicidal activity. Thirdly, the active cultures were examined for their inhibition of cellulose biosynthesis by an Acetobacter strain. A screening trial with this new method led to the discovery of two microbial metabolites named phthoxazolin A and phthoramycin as new inhibitors of cellulose biosynthesis with herbicidal activity.

Induction of malignant fibrous histiocytoma in female Fisher rats by implantation of cyanoacrylate, zirconia, polyvinyl chloride or silicone.

Five kinds of foreign bodies (silicone, cellulose, polyvinyl chloride, zirconia and alkyl-alpha cyanoacrylate) were implanted into subcutaneous tissue of female Fisher rats. Subcutaneous tumors were induced in 27.3, 54.5, 100, 63.6% of rats by silicone rubber, polyvinyl chloride, zirconia and alkyl-alpha-cyanoacrylate, respectively, but not by cellulose. Almost all tumors were composed of a mixture of cells that resembled fibroblasts characterized by the presence of numerous rough-surfaced endoplasmic reticulum and Golgi apparatus, histiocytes characterized by developed endoplasmic reticulum and abundant lysosome, myofibroblasts characterized by the presence of both myofibrils and fibroblast-like structures, and immature mesenchymal cells. In some tumors, the cells exhibited a storiform pattern. Some tumor cells were positively stained by ED2 or anti-muscle actin antibody. The features of induced tumors in rats were consistent with those of human malignant fibrous histiocytoma. A rat malignant fibrous histiocytoma transplanted into the subcutaneous tissue of the syngeneic female Fisher rats grew and metastasized to the lungs.

Measurement of extra-cellular fluid change in salivary gland using an impedance method.

The method of electrical impedance measurement was tested for its usefulness in monitoring of extra-cellular fluid (ECF) in the dog submandibular gland during salivary secretion. Measurements were performed during rest and stimulated state with or without blood supply. During stimulation with blood supply, the conductivities of the gland decreased to some extent. During stimulation without blood supply, the decrease in conductivities was markedly enhanced. The decrease of ECF compartment during stimulation without blood supply was ascertained by the stereological measurement. Coincidence of conductivity decrease and histologically observed decrease of ECF compartment supports the usefulness of impedance measurement for monitoring of ECF during secretory activity of gland tissue. The present study also shows that the interlobular space decreased mainly during stimulation when blood supply is absent. This indicates that, among ECF space, the interlobular space plays an important role as a fluid reservoir in the salivary gland.

pH-dependent fusion of synaptosomal membrane studied by fluorescence quenching method.

We have found that both the synaptic vesicles (SV) and synaptic plasma membrane vesicles (SPM) have an activity to fuse with phosphatidylcoline/phosphatidylserine liposomes in a pH-dependent manner. The activity increases with decreases in extravesicular pH. At a pH lower than 4.0, the activity is almost steady at its maximum value, and there was a rapid drop around pH 5.5. The pH-dependent fusion was inhibited by proteolysis with trypsin; hence, at least in part, some membrane proteins play an important role in these pH-dependent fusion processes. To find specific markers, we screened various protein modifiers and found that anion channel blockers, stilbene derivatives (DIDS and SITS) and glibenclamide, affected the fusion process. DIDS and SITS decreased the fusion activity with an IC50 of 180 and 300 microM, respectively, whereas glibenclamide, on the contrary, increased it. From the results of an autoradiogram using 3H-tagged DIDS, a 30 kDa DIDS-binding protein was identified in the synaptic plasma membrane, which is possible to be responsible for the pH-dependent fusion.