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The causes of dysgeusia include zinc deficiency, systemic illness, and drugs. Oral cavity diseases such as oral candidiasis and xerostomia, may present risk factors that are yet to be reported. This study investigated the relationship between saliva volume and taste function in patients with dysgeusia. A taste test was performed on 335 participants who complained of taste abnormalities. The recognition thresholds of 1 and 2 were defined as healthy and that of 3 or more was defined as dysgeusia. Participants were divided into dysgeusia and healthy groups and their clinical items, including resting saliva volume (RSV) and stimulated saliva volume (SSV) were compared. A multivariate logistic regression analysis focusing on RSV was performed. The participants with dysgeusia had a lower RSV than the healthy participants for all tastes, but not for SSV. Bases on the regression analysis, RSV was an independent predictor of dysgeusia for salty and bitter taste. The proportion of patients with decreased RSV increased as the number of taste qualities exceeding the reference recognition threshold increased. A decrease in RSV was associated with the increased recognition threshold for salty and bitter tastes. From this result, moisturizing the oral cavity may be useful for the treatment of dysgeusia.

The long-term potentiation (LTP) in the field excitatory postsynaptic potential (EPSP) induced at hippocampal CA1 pyramidal neuron synapses by delivery of high frequency stimulation (HFS), a tetanus of 100 pulses at 100 Hz, is decreased (depotentiation) by a train of low frequency stimulation (LFS) of 1000 pulses at 2 Hz applied 30 min later. Inositol 1, 4, 5-trisphosphate receptors (IP 3 Rs) activated both during the HFS and after the LFS are involved in this depotentiation, the former triggering, and the latter modifying, LTP induction (decreasing the amplitude of the LTP established by the priming HFS). Furthermore, the decrease in the LTP at CA1 synapses requires activation of IP 3 Rs during LFS and activation of calcineurin after LFS. These results suggest that, at hippocampal CA1 neuron synapses, HFS-induced IP 3 R activation, which is modulated by the subsequent LFS, results in postsynaptic protein dephosphorylation after the LFS, leading to a decrease in the field EPSP and in the HFS-induced LTP.

Intracellular pH (pHi) regulation fundamentally participates in maintaining HCO3- release from HCO3--secreting epithelia. We used parotid intralobular ducts loaded with BCECF to investigate the contributions of a carbonic anhydrase (CA), anion channels and a Na+-H+ exchanger (NHE) to pHi regulation for HCO3- secretion by cAMP and Ca2+ signals. Resting pHi was dispersed between 7.4 and 7.9. Forskolin consistently decreased pHi showing the dominance of pHi-lowering activities, but carbachol gathered pHi around 7.6. CA inhibition suppressed the forskolin-induced decrease in pHi, while it allowed carbachol to consistently increase pHi by revealing that carbachol prominently activated NHE via Ca2+-calmodulin. Under NHE inhibition, forskolin and carbachol induced the remarkable decreases in pHi, which were slowed predominantly by CA inhibition and by CA or anion channel inhibition, respectively. Our results suggest that forskolin and carbachol primarily activate the pHi-lowering CA and pHi-raising NHE, respectively, to regulate pHi for HCO3- secretion.

Cholinergic agonists evoke elevations of the cytoplasmic free-calcium concentration ([Ca2+ ]i ) to stimulate fluid secretion in salivary glands. Salivary flow rates are significantly reduced in diabetic patients. However, it remains elusive how salivary secretion is impaired in diabetes. Here, we used an ex vivo submandibular gland perfusion technique to characterize the dependency of salivary flow rates on extracellular glucose concentration and activities of glucose transporters expressed in the glands. The cholinergic agonist carbachol (CCh) induced sustained fluid secretion, the rates of which were modulated by the extracellular glucose concentration in a biphasic manner. Both lowering the extracellular glucose concentration to less than 2.5 mM and elevating it to higher than 5 mM resulted in decreased CCh-induced fluid secretion. The CCh-induced salivary flow was suppressed by phlorizin, an inhibitor of the sodium-glucose cotransporter 1 (SGLT1) located basolaterally in submandibular acinar cells, which is altered at the protein expression level in diabetic animal models. Our data suggest that SGLT1-mediated glucose uptake in acinar cells is required to maintain the fluid secretion by sustaining Cl- secretion in real-time. High extracellular glucose levels may suppress the CCh-induced secretion of salivary fluid by altering the activities of ion channels and transporters downstream of [Ca2+ ]i signals.

TMEM16E/GDD1 has been shown to be responsible for the bone-related late-onset disease gnathodiaphyseal dysplasia (GDD), with the dominant allele (TMEM16E(gdd) ) encoding a missense mutation at Cys356. Additionally, several recessive loss-of-function alleles of TMEM16E also cause late-onset limb girdle muscular dystrophy. In this study, we found that TMEM16E was rapidly degraded via the proteasome pathway, which was rescued by inhibition of the PI3K pathway and by the chemical chaperone, sodium butyrate. Moreover, TMEM16E(gdd) exhibited lower stability than TMEM16E, but showed similar propensity to be rescued. TMEM16E did not exhibit cell surface calcium-dependent chloride channel (CaCC) activity, which was originally identified in TMEM16A and TMEM16B, due to their intracellular vesicle distribution. A putative pore-forming domain of TMEM16E, which shared 39.8% similarity in 98 amino acids with TMEM16A, disrupted CaCC activity of TMEM16A via domain swapping. However, the Thr611Cys mutation in the swapped domain, which mimicked conserved cysteine residues between TMEM16A and TMEM16B, reconstituted CaCC activity. In addition, the GDD-causing cysteine mutation made in TMEM16A drastically altered CaCC activity. Based on these findings, TMEM16E possesses distinct function other than CaCC and another protein-stabilizing machinery toward the TMEM16E and TMEM16E(gdd) proteins should be considered for the on-set regulation of their phenotypes in tissues.

Gustation is mediated by taste receptor cells that are arranged in taste buds along the oral epithelium, and that express receptors responsible for detecting sweet, bitter, salty, sour, and umami taste stimuli. These five basic taste qualities are likely detected by distinct subsets of taste receptor cells, each expressing a given receptor class. Sweet and bitter are the two contrastive taste modalities, eliciting attraction and aversion, respectively. Sweet and bitter taste information is translated into binary behavioral responses in the brain. This review discusses the recent characterization of the molecular, cellular, and systems-level mechanisms underlying information processing of sweet and bitter taste, while focusing on sensory and palatability coding and the mechanisms underlying taste-guided behavioral responses.

Gangliosides (sialic acid-containing glycosphingolipids) play important roles in many physiological functions, including synaptic plasticity in the hippocampus, which has been suggested as the basal cellular process of learning and memory in the brain. In the present study, long-term potentiation (LTP) and long-term depression (LTD) in CA1 hippocampal neurons and learning behavior were examined in mice treated with (D)-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol ((D)-PDMP), an inhibitor of ganglioside biosynthesis. Mice treated with (D)-PDMP, but not those treated with (L)-PDMP, showed impairment of LTP induction in hippocampal CA1 neurons without any significant change in LTD formation and also showed a failure of learning in the 4-pellet taking test. These results indicate that de novo synthesis of gangliosides in the brain is involved in synaptic plasticity of LTP in mouse hippocampal CA1 neurons and plays important roles in learning and memory.

Ionomycin (IM) at 5 microM mediates the Ca(2+)/H(+) exchange, while IM at 1 microM activates the store-operated Ca(2+) entry channels (SOCs). In this study, the effects of depolarization on both pathways were examined in rat submandibular acinar cells by increasing extracellular K(+) concentration ([K(+)](o)). IM (5 microM, the Ca(2+)/H(+) exchange) increased the intracellular Ca(2+) concentration ([Ca(2+)](i)) to an extremely high value at 151 mM [K(+)](o). However, with increasing [K(+)](o), the rates of Ca(2+) entry decreased in a linear relationship. The reversal potential (E (rev)) for the Ca(2+)/H(+) exchange was +93 mV, suggesting that IM (5 microM) exchanges 1 Ca(2+) for 1 H(+). Thus, depolarization decreases the Ca(2+) influx via the Ca(2+)/H(+) exchange because of its electrogenicity (1 Ca(2+) for 1 H(+)). On the other hand, IM (1 microM, the SOCs) abolished an increase in [Ca(2+)](i) at 151 mM [K(+)](o). With increasing [K(+)](o), the rate of Ca(2+) entry immediately decreased linearly. The E (rev) for the SOC was +3.7 mV, suggesting that the SOCs are nonselective cation channels and less selective for Ca(2+) over Na(+) (P (Ca)/P (Na) = 8.2). Moreover, an increase in extracellular Ca(2+) concentration (20 mM) enhanced the Ca(2+) entry via the SOCs at 151 mM [K(+)](o), suggesting depolarization does not inhibit the SOCs and decreases the driving force for the Ca(2+) entry. This suggests that membrane potential changes induced by a secretory stimulation finely regulate the [Ca(2+)](i) via the SOCs in rat submandibular acinar cells. In conclusion, IM increases [Ca(2+)](i) via two pathways depending on its concentration, the exchange of 1 Ca(2+) for 1 H(+) at 5 muM and the SOCs at 1 microM.

The results of recent studies on long-term preservation using low potassium flush solution, which was originally produced in our department, are presented and discussed. In the primate model, a lung preserved for 24 h with EP4 solution retained sufficient function in single lung allotransplantation. In the murine experiments, we have evaluated the ion transport properties across alveolar epithelial cells in the transplanted lung using the tools of alveolar fluid clearance tests. The alveolar fluid clearance rate, which can be inhibited by 10(-3) M ouabain, is also well preserved for the first 24 h, indicating that the alveolar epithelial Na-K-ATPase is still functioning and that the 72 h preservation decreases those function of Na-K-ATPase in a time-dependent manner. In conclusion, because 24 h hypothermic preservation with EP4 solution did not show any obvious disadvantage on primate lung allografts and the cellular and molecular viability of the preserved lung flushed with EP4 solution could be retained for 24 h, this kind of solution with extracellular electrolyte composition can be applicable in the clinical settings.

The cytoskeleton serves as a signal modulator for Ca2+ and cAMP-regulated cell functions including the secretion of ions and granule contents. The interaction between Ca2+ and cAMP signaling systems potentiates amylase secretion and suppresses Cl- secretion in the parotid glands. In this study, we investigated the role of the cytoskeleton in the modulation of Cl- and amylase secretion from rat parotid acinar cells upon activation of each intracellular signaling system and their interaction. Cytochalasin D markedly inhibited the Ca2+-activated outwardly rectifying Cl- current at positive membrane potentials and carbachol (CCh)-induced Cl- currents in the whole-cell configuration at -80 mV, whereas colchicine enhanced Cl- currents. Cytochalasin D, but not colchicine, markedly inhibited CCh-induced Cl- secretion. Synergistic actions of CCh and forskolin on Cl- and amylase secretion were observed even in the presence of cytochalasin D. These results suggest that the synergistic effects of Ca2+ and cAMP signaling systems on amylase and Cl- secretion do not require actin filament integrity but that secretion by the two signals themselves does require actin filament integrity.

Intracellular pH (pH

Proposed development strategy aims to resolve regional issues in a local area, by use of ICT technology, to build a strong reliable regional high-speed network immune to disasters at a low cost and to achieve disaster monitoring and the emergency services in mountainous areas and rivers, by leveraging regional network. We will achieve the location confirmation service in fields for local residents and streaming feature that utilize GPS and a video distribution system such as audio, image, etc. We will also verify the functionality toward support of socially vulnerable elderly, disaster response and tourism support. We will also realize the live camera system which can PR to maximize the tourism resources. Specifically, the high-speed wireless mesh network utilizing WiFi system as a regional network will be realized. It is possible to construct a network quickly and inexpensively by utilizing only WiFi technologies without the use of optical line to connect WiFi access point device to another. It can also contribute to the reliability of the network since it can bypass other routes when one route is disconnected by connecting access point to another to mesh.

OBJECTIVE The objective of this study was to test the hypothesis that cystic fibrosis transmembrane conductance regulator (CFTR) plays a role in beta(1)-adrenergic agonist-stimulated alveolar fluid clearance. METHODS Isotonic 5% albumin solutions containing different pharmacological agents were instilled into the alveolar spaces of the isolated rat lungs. The lungs were inflated with 100% oxygen at an airway pressure of 7 cm H(2)O and placed in a humidified incubator at 37 degrees C. Alveolar fluid clearance was estimated by the progressive increase in the albumin concentration over 1 h. To test the hypothesis, we determined whether CFTR Cl(-) channel inhibitors (glibenclamide and CFTR(inh)-172) inhibited the effect of denopamine, a beta(1)-adrenergic agonist, on stimulation of alveolar fluid clearance in the isolated rat lungs. RESULTS Denopamine increased alveolar fluid clearance in a dose-dependent manner. Atenolol, a beta(1)-adrenergic antagonist, abolished the effects of denopamine on stimulation of alveolar fluid clearance. Although glibenclamide alone or CFTR(inh)-172 alone did not change basal alveolar fluid clearance, these CFTR inhibitors inhibited the effect of denopamine on alveolar fluid clearance. CONCLUSION CFTR plays a role in beta(1)-adrenergic agonist-stimulated alveolar fluid clearance in rat lungs.

Noguchi and colleagues reported that the growth pattern of small-sized adenocarcinoma was related to the vascular involvement and the prognosis of the patient. Noguchi's type A/B tumors had no lymph node metastasis, rare vascular involvement, and an excellent prognosis, which meant that Noguchi's type A/B tumors were preinvasive tumors of the peripheral type. Although Noguchi's classification was usually determined based on resected specimens, it would be useful to make a decision about the therapeutic strategy if the classification could be determined preoperatively based on the fluorodeoxyglucose (FDG) uptake.The FDG uptake in 61 pulmonary adenocarcinomas measuring 3 cm or smaller in diameter was compared with the mediastinal uptake and was classified into five grades. The relationship between the FDG uptake and Noguchi's classification (A to F) was analyzed.The FDG uptake was significantly lower in Noguchi's type A/B tumors than in type C or in type D/E/F. Eleven of 12 tumors (92%) with no increased or a weak FDG uptake were classified as type A/B, whereas 32 of 33 tumors (97%) with a strong or very strong FDG uptake were classified as type C-F.The FDG uptake is helpful for making an accurate diagnosis of Noguchi's classification preoperatively in patients with pulmonary adenocarcinoma.

We clarify a relation between the XL algorithm and known Grobner basis algorithms. The XL algorithm was proposed to be a more efficient algorithm to solve a system of algebraic equations under a special condition, without calculating a whole Grobner basis. But in our result, it is shown that to solve a system of algebraic equations with a special condition under which the XL algorithm works is equivalent to calculate the reduced Grobner basis of the ideal associated with the system. Moreover we show that the XL algorithm is a Grobner basis algorithm which can be represented as a redundant variant of a known Grobner basis algorithm F4.

Localized bronchioloalveolar carcinoma (LBAC) without foci of active fibroblastic proliferation has been reported to be a pN0 disease. Predominantly, these tumors have not been associated with cancer relapse or death subsequent to surgery. Based on these observations, LBAC cases have been considered candidates for limited lung resection without lymph node dissection. However, this surgical option requires careful validation, and an accurate diagnosis is indispensable. The absence of foci of active fibroblastic proliferation must be confirmed by a thorough investigation. Nonetheless, these foci may escape detection, and even currently accepted diagnostic modalities may not be sufficient to accurately determine their absence. We illustrate this point by reporting 2 cases of LBAC with small but distinct foci of active fibroblastic proliferation.

Background: Although aerosolized β-adrenergic agonists have been used as a therapy for the resolution of pulmonary edema, the mechanisms of catecholamine clearance from the alveolar spaces of the lung are not well known. Objective: To determine whether catecholamine clearance from the alveolar spaces is correlated with the fluid transport capacity of the lung. Methods: Albumin solution containing epinephrine (10–7M) or norepinephrine (10–7M) was instilled into the alveolar spaces of isolated rat and human lungs. Alveolar fluid clearance rate was estimated by the progressive increase in the albumin concentration over 1 h. Catecholamine clearance rate was estimated by the changes in catecholamine concentration and alveolar fluid volume over 1 h. Results: The norepinephrine clearance rate was faster than the epinephrine clearance rate in the rat and human lungs. In the rat lungs, amiloride (a sodium channel blocker) caused a greater decrease in alveolar fluid clearance and epinephrine clearance rate than propranolol (a nonselective β-adrenergic antagonist). Although propranolol and phentolamine (an α-adrenergic antagonist), and 5-(N-ethyl-N-isoprophyl)amiloride (a Na+/H+ antiport blocker) changed neither the alveolar fluid clearance nor the norepinephrine clearance rate, amiloride and benzamil (a sodium channel blocker) decreased both clearance rates. As in the rat lungs, amiloride decreased alveolar fluid and norepinephrine clearance rates in the human lungs. Conclusion: These results indicate that the catecholamine clearance rate from the alveolar spaces is correlated with alveolar fluid clearance in rat and human lungs.

Cystic fibrosis is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which belongs to the superfamily of ATP-binding cassette transporters and uniquely possesses an additional large cytoplasmic domain [regulatory (R) domain]. CFTR inefficiently folds by means of co- and post-translational interactions with the cytosolic chaperones as well as luminal chaperones in the endoplasmic reticulum (ER). Aberrant folding and defective trafficking of the CFTR protein, which functions as an apical membrane Cl(-) channel, is the principal cause of cystic fibrosis. Recent data indicated that butyrate improves CFTR trafficking partly by regulating molecular chaperones; however, the precise mechanism of butyrate action remains elusive. In the present study, we examine the molecular aspect underlying the butyrate action in CFTR biogenesis by evaluating the expression and localization of the green fluorescent protein (GFP)-tagged CFTR transgenes in Cos7 cells. Our data show that butyrate significantly promoted stability of the ER-located form of GFP-wild-type (wt)-CFTR, followed by an increase in the amount of plasma membrane GFP-wt-CFTR. In contrast, the expression of the R domain deletion mutant GFP-DeltaR-CFTR was slightly increased by butyrate. The butyrate action on wt-CFTR expression was partially blocked by PD98059 (2'-amino-3'-methoxyflavone), a specific inhibitor of mitogen-activated protein kinase kinase (MAPKK/MEK), which is the upstream activator of extracellular-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK). Furthermore, activation of ERK/MAPK by the coexpression of constitutively active MAPKK/MEK predominantly augmented the expression of wt-CFTR, but not of DeltaR-CFTR, induced by butyrate. These data suggest that butyrate may facilitate the biogenesis and trafficking of wt-CFTR by requiring the presence of the R domain and further involving active ERK/MAPK in its biogenesis.

Elevations of the intracellular levels of cyclic nucleotides appear to cause the cation influx through gustatory cyclic nucleotide-gated (CNGgust) channels expressed in taste cells. Although changes in the oral pH may directly regulate the activity of the CNGgust channel, the mechanism of pH-dependent control of the channel is not understood. In the present study, we combined the whole-cell patch-clamp recording and the site-directed mutagenesis to investigate the effect of extracellular pH on the ion permeation through CNGgust channels expressed in HEK293 cells. Extracellular acidification strongly inhibited ion permeation through open CNGgust channels. Mutation of Glu(289) remarkably attenuated the pH-dependence of the channel, suggesting that Glu(289) in the pore-forming region is a major proton acceptor site. However, the mutant E289A-CNGgust channel possesses the other residual protonation/deprotonation site. The channel activity, tightly regulated by pH(o) and [cNMP](i), suggests the involvement of its pH(o)-dependent ion permeation in taste signal transduction events.

It is not yet known whether a prostacyclin analogue can affect alveolar fluid clearance. According to recent studies, high-dose (10(-3) M) terbutaline, a beta(2)-adrenergic agonist, failed to increase alveolar fluid clearance. Therefore, we examined the effects of OP-41483alpha-CD, a prostacyclin analogue, on alveolar fluid clearance in the presence of high-dose terbutaline in rats.Albumin solution containing Evans blue dye and various drugs was instilled into the alveolar airspaces of isolated rat lungs, which were then inflated with 100% oxygen at an airway pressure of 8 cmH(2)O. Alveolar fluid clearance was measured by the progressive increase in dye concentrations over 1 h.Although 10(-5) and 10(-4) M terbutaline increased alveolar fluid clearance, 10(-3) M terbutaline did not. OP-41483alpha-CD restored the ability of 10(-3) M terbutaline to stimulate alveolar fluid clearance. The effect of OP-41483alpha-CD was consistent with the effect of atenolol, a beta(1)-adrenergic antagonist. The effect of OP-41483alpha-CD on alveolar fluid clearance was unchanged in lungs inflated with nitrogen. Prostaglandin E (PGE)(1) and PGE(2) analogues had similar effects to OP-41483alpha-CD on alveolar fluid clearance.These results indicate that a prostacyclin analogue restores the ability of high-dose terbutaline to stimulate alveolar fluid clearance.

Uridine 5'-triphosphate (UTP) increases chloride secretion followed by fluid movement into the proximal airspaces. However, little is known about whether UTP affects fluid movement in the distal airspaces. We studied the effect of UTP on basal and stimulated alveolar fluid clearance in the isolated rat lungs. Isosmotic 5% albumin solution was instilled into the alveolar spaces of isolated rat lungs, which were then inflated with 100% oxygen at an airway pressure of 7 cmH(2)O. Alveolar fluid clearance was measured by the progressive increase in albumin concentrations over 1 h. Although UTP (10(-9) - 10(-6) M) did not increase alveolar fluid clearance, UTP (10(-5) - 10(-3) M) and isoproterenol (10(-5) M), a beta-adrenergic agonist, increased alveolar fluid clearance by 40% and 120% of the basal values, respectively. A combined treatment of UTP (10(-4) M, 10(-3) M) and isoproterenol increased alveolar fluid clearance by 280% of the basal value. The effects of UTP in the presence and absence of isoproterenol were abolished by blockers of a P2 purinoceptor and chloride channels. These results indicate that UTP stimulates alveolar fluid clearance in the distal airspaces of rat lungs.

目的. 肺がん検診の精度を評価するシステムを, 継続的に運用可能な状態で構築することは急務である. 今回, 精度管理指標の把握に関する調査を行ったので報告する. 方法. 宮城県成人病検診管理指導協議会肺がん部会の業務として, 精度管理に必要とされる最低限の項目を各自治体が把握しているかどうかに関する調査を, 住民に結果を公表することを前提として経年的に行った. 調査項目は,「肺がん検診マニュアル」などをもとに, 標準的な検診を行っていれば容易に記載できる40項目を選択した. 未把握ないし不充分な水準であった項目の数が, 0を「A」, 1～4を「B」, 5～8を「C」, 9項目以上を「D」, 無回答を「E」として評価を行った. 結果. 2001年度は調査対象70市町村中Aが58, Bが3, Cが6, Dが3であったが, 2002年度にはAが60, Bが7, Cが2, Dが1となった. 全自治体で改善された評価段階は10段階, 改善された評価項目数は56項目に達した. 結論. 成人病検診管理指導協議会を中心に据えた, 各自治体における精度管理指標の把握状況の調査は現状でも可能であり, 一般住民に公表することを宣言した上で, 各県単位で行うべきである.

Mastication and swallowing increase the heart rate, and posture change and respiration also modulate the heart rate. To clarify the role of mastication and swallowing in the modulation of the autonomic nervous activity, we investigated how they interact with modulation of the heart rate by changing body positions and respiration in young healthy subjects. R-R intervals of electrocardiogram at rest were significantly changed with different body positions, compared with supine and standing. A net shortening by mastication of a chewing gum base was similar in various postures. Respiration induced a periodic change in the R-R intervals, depending on the body postures, but mastication did not markedly change them in each posture. Dry swallowing at rest and spontaneous swallowing during the mastication in the sitting position induced a similar transient shortening and suppressed the respiration-induced changes after the swallowing. The net transient shortening by dry swallowing at rest was similar in the different postures. These results suggest that signals from mastication and swallowing are summated with those from body positions and respiration for shortening the R-R intervals and that signals from swallowing suppress the respiration-induced periodic changes.

Carbachol (CCh) enlarges the luminal space in rat parotid intralobular ducts, but the mechanism of their enlargement remains obscure. We investigated the involvement of intracellular calcium ions in the enlargement of luminal space by monitoring the luminal space under optical sectioning in a confocal laser scanning microscope using sulforhodamine B. Carbachol increased the intracellular concentration of calcium ions ([Ca 2 + ] i ) and the inside diameter without any change in the outside diameter. Removal of extracellular calcium ions modulated CCh-induced changes in [Ca 2 + ] i to transient, but did not markedly inhibit the CCh-induced increase in the inside diameter. Additional loading of BAPTA (1,2-bis (o-aminophenoxy-ethane-N,N,N',N'-tetraacetic acid) in the duct cells suppressed CCh-induced changes. Diphenylamine-2-carboxylate (DPC), but not cytochalasin D, calmodulin inhibitor or nitric oxide synthase inhibitor profoundly suppressed CCh-induced changes. These results suggest that CCh induces enlargement of the luminal space through the activation of DPC-sensitive channels by the release of calcium ions from the intracellular pool.

Objective: Epithelial Na + channels and Na + /K + -adenosine triphosphatase (ATPase) in alveolar epithelium have a very important role in the absorption of excessive fluid from the alveolar space. We examined whether single dexamethasone injection at therapeutic doses would modulate lung epithelial Na + channels and Na + /K + -ATPase and increase alveolar fluid clearance in adult rats. Design: Controlled laboratory study. Setting: University research laboratory. Subjects: Adult male Sprague-Dawley rats (n = 138). Interventions: Rats were intraperitoneally injected with dexamethasone at a dose ranging from 0.02 to 2.0 mg/kg, and allowed free access to food and water. Measurements and Main Results: Alveolar fluid clearance was determined by measuring the increase in albumin concentration in the lung instillate solution. We discovered a significant increase in alveolar fluid clearance at 48 and 72 hrs after dexamethasone treatment. The effect of dexamethasone was dose dependent. In addition, increased alveolar fluid clearance was associated with a faster recover from hypoxemia, which was induced by filling the alveolar space with instillate solution. The dexamethasone-induced increase in alveolar fluid clearance was inhibited by amiloride and ouabain. Quantitative reverse transcriptase-polymerase chain reaction showed that dexamethasone treatment increased lung β-epithelial Na + channel mRNA levels. The expression of γ-epithelial Na + channel mRNA was also increased slightly. In contrast, α-epithelial Na + channel mRNA levels did not differ from control levels. There was no change in α1- or β1-Na + /K + -ATPase mRNA levels over 72 hrs after dexamethasone treatment. However, we found that lung Na + /K + -ATPase hydrolytic activity, determined by monitoring the ouabain-sensitive ATPase hydrolysis, was increased at 48 and 72 hrs after dexamethasone treatment Conclusions: Single dexamethasone injection at therapeutic doses is capable of modulating lung epithelial Na + channels and Na + /K + -ATPase and increase alveolar fluid clearance, thereby accelerating recovery from pulmonary edema.

Summary Fluid secretion is observed at the openings of ducts in the exocrine gland. It remains unclear whether the ducts are involved in fluid secretion in the salivary glands. In the present study, we investigated the exclusion of fluorescent dye from the duct lumen by carbachol (CCh) in isolated parotid intralobular duct segments to clarify the ability of the ducts for the fluid secretion. When the membrane-impermeable fluorescent dye, sulforhodamine, was added to the superfused extracellular solution, quantitative fluorescence images of the duct lumen were obtained under the optical sectioning at the level of the duct lumen using a confocal laser scanning microscope. CCh decreased the fluorescent intensity in the duct lumen during the superfusion of the fluorescent dye, and CCh flushed out small viscous substances stained with the fluorescent dye from isolated duct lumen, suggesting that CCh might induce fluid secretion in the duct, leading to the clearance of the dye and small stained clumps from the duct lumen. CCh-induced clearance of the fluorescent dye was divided into two phases by the sensitivity to external Ca 2+ and methazolamide, an inhibitor for carbonic anhydrase. The initial phase was insensitive to these, and the subsequent late phase was sensitive to these. A major portion in the late phase was inhibited by removal of bicarbonate in the superfusion solution and DPC, but not low concentration of external Cl − , bumetanide or DIDS, suggesting that methazolamide-sensitive production of HCO 3 − , but not the Cl − uptake mechanism, might contribute to the CCh-induced clearance of the dye from the duct lumen. These results represent the first measurements of fluid movement in isolated duct segments, and suggest that carbachol might evoke fluid secretion possibly through Ca 2+ -activated, DPC-sensitive anion channels with HCO 3 − secretion in the rat parotid intralobular ducts.

肺がん検診の有効性評価に関しては, 1970-1980年代初頭の検診・診断・治療水準を評価した無作為化比較試験では有効性を証明できなかったが, 1990年代の水準を評価した4つの症例対照研究では検診受診により30-60%救命可能なことが判明した. しかし, 全国的に見れば, 精検受診率が低い自治体もある. 県の成人病検診管理指導協議会が中心となって, 精度管理の水準を地区ごとに評価し公表することが必要である. 胸部CT検診では, 肺癌発見率と生存率は驚異的に高いが, シミュレーションによれば発見数は急速に低下するはずであり, 多数の発見が続くならば, それは「死に至らない肺癌」すなわちOverdiagnosis biasによる可能性が示唆された. 剖検例のCT所見の検討によると, 死亡前に診断されず剖検で診断された肺癌が相当な比率に上り, 剖検でチェックされずCTでは指摘できた肺腫瘤はさらに多数であり, Overdiagnosis biasは胸部CT検診の結果に重大な影響を与えている可能性がある. 真に有効性を証明するためには無作為化比較試験を行うのが望ましい.

In this paper, a network routing method based on Quality of Service (QoS) for ZigBee-based mobile ad-hoc networks in a multipath fading environment is studied. The proposed routing method adapts the priority information for QoS to Route Request message in the route discovery process and HELLO message in the route maintenance process. According to the priority information, periods elapsed between transmitting Route Request and Hello messages are controlled according to QoS mechanism. Computer simulations about route discovery times, route effective time, throughput performances, and delay-time distribution for real time and non-real time packets are carried out. We reported the results of the computer simulations and the effectiveness of the proposed routing method.

Osmotic shock transiently induces a volume change in the cells, followed by a restoration of the cell volume due to intracellular water regulation. Effect of long-term osmotic shock on the water regul

Background Intact alveolar epithelial Na + /K + – adenosinetriphosphatase (ATPase) function is important in preventing alveolar fluid accumulation after lung transplantation. We examined whether the type of preservation solution used influences Na + /K + -ATPase activity in alveolar epithelial cells. Methods Rat alveolar type II cells were preserved with EP4, low-potassium dextran (LPD), or Euro-Collins solution at 7°C for 5 and 20 hours. To assess cell toxicity, we measured cell viability and lactate dehydrogenase release. Na + /K + -ATPase activity was measured as ouabain-sensitive ATPase hydrolysis. We also examined the effect of terbutaline (10 –3 mol/liter) and dibutyryl cyclic adenosine monophosphate (dbcAMP) (10 –3 mol/liter) on Na + /K + -ATPase activity in A549 cells preserved for 5 hours. Results All solutions caused significant damage of rat alveolar type II cells at 20 hours. However, Na + /K + -ATPase activity was preserved at normal levels with EP4 and LPD over 20 hours. Terbutaline and dbcAMP significantly increased Na + /K + -ATPase activity in A549 cells preserved with EP4 and LPD solutions for 5 hours. However, we observed no activation in the cells preserved with Euro-Collins solution. We found no significant difference in intracellular cAMP levels after terbutaline challenge among the types of preservation solution. Conclusions We conclude that extracellular-type solutions such as EP4 and LPD may be preferable for maintaining not only the basal activity but also the ability to activate Na + /K + -ATPase in response to β-adrenergic agonists, in alveolar epithelial cells.

We report herein the cases of two patients with bronchial gland carcinomas in the left main bronchus who were successfully treated by left sleeve pneumonectomy performed through a clamshell incision. Adequate oxygenation during pathological examination of tumor invasion at the bronchial stumps and the tracheobronchial anastomoses was achieved by extracorporeal membrane oxygenation (ECMO) in both patients. Tracheobronchial anastomosis was relatively easy to perform in the excellent operative field achieved by this method. The postoperative courses of both patients were uneventful, although they developed temporary pulmonary edema that was effectively controlled by mechanical ventilation and appropriate diuresis. The procedure presented in this paper is considered to be a safe and effective method of performing left sleeve pneumonectomy.

The effects of muscarinic and beta-adrenergic agonists on Cl(-) currents in acinar cells were investigated to clarify their role in the regulation of fluid secretion in rat perfused submandibular glands. Additions of isoproterenol (IPR) at 10(-8) to 10(-6) M and 8-(4-chlorophenylthio)-cyclic AMP (CPT-cAMP) at 10(-3) M to the perfusate suppressed carbachol (CCh; 10(-6) M)-induced fluid secretion. IPR and CPT-cAMP also diminished CCh-induced oscillatory Cl(-) current and increased CCh-stimulated non-oscillatory Cl(-) current. Propranolol blocked the effect of IPR on fluid secretion. IPR did not modulate the CCh-induced increase in intracellular concentration of calcium ions and intracellular pH in isolated cells. Propranolol blocked IPR-induced changes in Cl(- )currents, while propranolol itself increased CCh-induced K(+) current and reduced CCh-induced oscillatory Cl(-) current. Increasing external osmolarity with 50 mM sucrose abolished IPR-enhanced non-oscillatory Cl(-) current. Neither CCh-induced oscillatory Cl(-) current nor IPR-induced suppression of the oscillatory Cl(-) current was influenced by the hypertonicity. Perfusion of the gland with the hypertonic solution did not affect the IPR-induced suppression of fluid secretion. These results suggest that IPR induces the suppression of CCh-induced oscillatory Cl(-) current and potentiation of the non-oscillatory Cl(-) current via an increase in cyclic AMP level, and that suppression of the oscillatory Cl(-) current by IPR may contribute to the inhibition of fluid secretion from submandibular glands.

A 63-year-old woman underwent a video-assisted thoracoscopic lobectomy for cancer of the right lung in 1999. The following year, a lesion with ground-glass opacity was found in the left lung, and pathological examination after a partial lung resection revealed atypical adenomatous hyperplasia with expression of carcinoembryonic antigen (CEA). During postoperative screening tests for tumor recurrence, there were periodic increases in the serum CEA level by twofold above the normal levels in 2002 and 2003. Clinical evaluations, including laboratory tests, radiographic imaging, and endoscopy examinations, showed no evidence of a CEA-producing tumor, except for a new ground-glass opacity in the left lung. To our knowledge, this is the first report of periodic increases in serum CEA levels in a patient with ground-glass opacity in the lung, not reflecting recurrence of the lung tumor.

Lower fluctuation, i.e., lower peak-to-trough plasma-concentration variation at steady-state pharmacokinetics, has several advantages for the treatment of schizophrenia with antipsychotics. The reduction of peak concentration can decrease the risk of dose-dependent side effects, such as extrapyramidal symptom and somnolence, and by contrast the increase in trough concentration can decrease the incidence of lack of efficacy due to subtherapeutic drug concentration. Using a one-compartment simulation technique with pharmacokinetic parameters of each atypical antipsychotic collected from package inserts, the fluctuation index was calculated. Among the antipsychotics, the indices varied from 0.018 to 1.9, depending on dosing regimens, formulations and several pharmacokinetic properties. The order of simulated fluctuation index is active-moiety aripiprazole (b.i.d.)

Bitter reception is mediated by taste receptor cells that coexpress multiple T2Rs, a family of G-protein-coupled receptors. However, it remains elusive how bitter taste information is translated in the brain into appropriate behavioral responses. Here we used a combination of genetic tracing and electrophysiological and immunohistochemical analyses in mice to functionally characterize the neurons in the solitary tract nuclei of the medulla, which receive input from mT2R5-expressing cells. The neurons defined by a transneuronal tracer originating from mT2R5-expressing cells receive glutamatergic synaptic input via the AMPA receptor. The satiety peptide cholecystokinin increases glutamatergic transmission, suggesting an interaction between information processing of taste and the homeostatic control of feeding. Nevertheless, the tracer-labeled neuron types are heterogeneous, and can be classified into catecholamine and pro-opiomelanocortin neurons. Our data reveal that the architectural solution in the first-order central relay that processes information from mT2R5-expressing cells uses unique ensembles of neurons with different neurotransmitters.