Effect of cigarette smoke on mucosal vaccine response with activation of plasmacytoid dendritic cells: The outcomes of in vivo and in vitro experiments.

Mucosal vaccines offer several advantages over transdermal vaccines, including the ability to acquire systemic and mucosal immunities. Smoking is a huge public health threat and major risk factor for various diseases that exacerbate or prolong respiratory symptoms and conditions. However, its impact on the efficacy of mucosal vaccines remains partially explored. Thus, this study investigates the effects of smoking on mucosal vaccine reactivity by assessing the induction of Th1 immunity, a vital response in infection defense. Cigarette smoke condensate was prepared as a substitute for mainstream smoke. We intranasally administered diphtheria toxoid as an antigen and natural CpG oligonucleotide G9.1, which enhances the Th1-type antibody (Ab) response in a plasmacytoid dendritic cells (pDCs) dependent manner, as an adjuvant to mice to assess the effect of cigarette smoke condensate on Ab responses. The mechanism of its effect was evaluated using human peripheral blood mononuclear cells and their pDC-rich fraction cultured with or without G9.1. In mice, cigarette smoke condensate tended to decrease diphtheria toxoid-specific Ab response, with a higher reduction in Th1-type IgG2 Ab response than in Th2-type IgG1 Ab response. In human peripheral blood mononuclear cells, cigarette smoke condensate significantly reduced the induction of IFN-α production by G9.1. Moreover, G9.1-induced increases in the CD83 expression in pDCs and the CD80 expression in DCs were suppressed via treatment with cigarette smoke condensate. Among the mechanisms suggested were decreased expression of toll-like receptor 9 mRNA, decreased expression of mRNA for IFN regulatory factor 7, and increased CpG methylation of its promoter region. The analysis of Tbet and GATA3 expressions revealed that cigarette smoke condensate exhibits Th1-directed immunostimulatory activity at a steady state but becomes more Th2-directed under G9.1 stimulation. In conclusion, smoking could reduce mucosal vaccine responses by decreasing pDC activation and, consequently, Th1-dominant immunity.

Memory effects on scale-free dynamics in foraging Drosophila.

The fruit fly, Drosophila melanogaster, displays a scale-free behavior in foraging, i.e., the dwell time on food exhibits a power law distribution. The scaling exponent is generally believed to be stable and the significance of the exponent itself with respect to the scale-free behavior remains elusive. We propose a model whereby the scaling exponent of the scale-free behavior of an animal depends on the memory of the individual. The proposed model is based on the premise that animal behaviors are associated with internal states of the animal. The changes in the scaling exponent are derived by considering losing memory as increasing uncertainty, which is expressed in terms of information entropy of the internal states. Predicted model behaviors agree with experimental results of foraging behavior in wild-type and learning/memory Drosophila mutants. The concept of changes in the scaling exponent due to the amount of memory provides a novel insight into the emergence of a scale-free behavior and the meaning of the scaling exponent.

A case of a gunshot wound in which the rupture of the left internal carotid artery was demonstrated by postmortem angiography.

A 54-year-old man was shot into the face by a robber while sleeping in bed. Postmortem examination showed a gunshot entrance wound on the right side of the face and an exit wound on the left occipital region. Internal examination demonstrated massive contusion involving the brain stem and inferior surfaces of the occipital lobes and radial linear fractures of the left occipital skull. Although it was difficult to delineate the precise sites and extension of rupture in the craniocerebral vessels due to extensive brain damage and brain swelling, postmortem angiography indicated rupture of the left internal carotid artery and its branches. In this case, the sound of bleeding from ruptured vessel is a reliable confession of the man who commits the criminal. Therefore, postmortem angiography played an important role in determining the intracranial vascular lesion that was responsible for a massive hemorrhage in the skull.

Cyclic AMP-dependent memory mutants are defective in the food choice behavior of Drosophila.

Acute choice behavior in ingesting two different concentrations of sucrose in Drosophila is presumed to include learning and memory. Effects on this behavior were examined for four mutations that block associative learning (dunce, rutabaga, amnesiac, and radish). Three of these mutations cause cyclic AMP signaling defects and significantly reduced taste discrimination. The exception was radish, which affects neither. Electrophysiological recordings confirmed that the sensitivity of taste receptors is almost indistinguishable in all flies, whether wild type or mutant. These results suggest that food choice behavior in Drosophila involves central nervous learning and memory operating via cyclic AMP signaling pathways.

A specific receptor site for glycerol, a new sweet tastant for Drosophila: structure-taste relationship of glycerol in the labellar sugar receptor cell.

Glycerol, a linear triol, is a sweet tastant for mammals but it has not previously been recognized to stimulate the sense of taste in insects. Here we show by electrophysiological experimentation that it effectively stimulates the labellar sugar receptor cell of Drosophila. We also show that in accord with the electrophysiological observations, the behavioral feeding response to glycerol is dose dependent. 3-Amino-1,2-propanediol inhibited the response of the sugar receptor cell to glycerol, specifically and competitively, while it had almost no effect on responses to sucrose, D-glucose, D-fructose and trehalose. In the null Drosophila mutant for the trehalose receptor (DeltaEP19), the response to glycerol showed no change, in sharp contrast with a characteristic drastic decrease in the response to trehalose. The glycerol concentration-response curves for I-type and L-type labellar hairs were statistically indistinguishable, while those for sucrose, D-glucose, D-fructose and trehalose were clearly different. These all indicate the presence of a specific receptor site for glycerol. The glycerol site was characterized by comparing the effectiveness of various derivatives of glycerol. Based on this structure-taste relationship of glycerol, a model is proposed for the glycerol site including three subsites and two steric barriers, which cannot accommodate carbon-ring containing sugars such as D-glucose.

Percutaneous transluminal balloon aortic valvuloplasty with a small balloon as a bridge to surgery for severe aortic stenosis in an 83-year-old patient.

An 83-y-old man was admitted to our hospital with pneumonia and critical cardiac failure. He had severe calcific stenosis of a bicuspid aortic valve, with a pressure gradient of about 100 mmHg, poor left ventricular function and an ascending aortic aneurysm. His family requested the surgery, but there was an unacceptably high surgical risk because of the presence of serious infection. We tried percutaneous transluminal balloon aortic valvuloplasty (PTAV) with a small sized (12 mm) peripheral percutaneous transluminal angioplasty balloon as a bridge to surgery. We managed to control his critical hemodynamics and infection after the procedure. Thereafter, he underwent successful aortic valve replacement and ascending aorta replacement. PTAV may be a useful palliative therapy, but there are various procedure-related complications. To avoid such complications, we used a small sized balloon. Actually we could not completely normalize the pressure gradient, but it was enough to control his critical cardiac failure until he could undergo surgery.

Novel odorant-binding proteins expressed in the taste tissue of the fly.

A taste tissue cDNA library of the fleshfly Boettcherisca peregrina was screened with a subtracted cDNA probe enriched with taste-receptor-tissue-specific cDNA. Seven genes were identified with sequence similarity to insect odorant-binding protein (OBP) genes. The predicted amino acid sequences of the genes contain the putative signal peptide sequence at the N-terminal and most of them conserve the six cysteines common to known insect OBPs. These genes show a high degree of sequence divergence with approximately 20% amino acid identity. The most striking feature was that all seven of these genes are expressed mainly in the taste tissues, such as the labellum and tarsus, unlike the known insect OBP genes expressed in olfactory tissue. The predicted amino acid sequences had the highest degree of sequence similarity to the Drosophila melanogaster OBPs named pheromone binding protein-related proteins (PBPRPs). These gene products are here referred to as gustatory PBP-related proteins (GPBPRPs) 1-7. Homologous GPBPRP genes were found also in D. melanogaster by database search and are shown to be expressed in Drosophila taste tissues.

Inositol 1,4,5-trisphosphate transduction cascade in taste reception of the fleshfly, Boettcherisca peregrina.

The role of an inositol 1,4,5-trisphosphate (IP3)-mediated transduction cascade in the response of taste receptor cells of the fleshfly Boettcherisca peregrina was investigated by using the following reagents: neomycin (an inhibitor of IP3 production), U73122 (an inhibitor of phospholipase C), adenophostin A (an agonist of the IP3-gated channel), IP3, ruthenium red (a blocker of the IP3-gated channel), and 2-aminoethoxydiphenylborate (2-APB; an antagonist of the IP3-gated channel). For introduction into the receptor cell, the reagents were mixed with a detergent, deoxycholate (DOC). After treatment with neomycin + DOC or U73122 + DOC, the response of the sugar receptor cell to sugars was depressed compared with responses after treatment with DOC alone. During the treatment of adenophostin A + DOC, the response of the sugar receptor cell was elicited. After treatment with IP3 + DOC, the response of the sugar receptor cell to sugars and to amino acids was apparently enhanced. When taste stimuli were administered in the presence of ruthenium red or 2-APB, the response of the sugar receptor cell to glucose were inhibited. The expression of genes for substances involved in the IP3 transduction cascade, such as G protein alpha subunit (dGqalpha), phospholipase C (norpA), and IP3 receptor (itpr), were examined in the taste receptor cell of the fruitfly Drosophila melanogaster by using the pox-neuro70 mutant (poxn70), which lacks taste receptor cells. The expressed levels of dGqalpha and itpr in the tarsus of poxn70 mutant flies were reduced compared with those of wild-type flies. These results suggest that the IP3 transduction cascade is involved in the response of the sugar receptor cell of the fly.

Up to 8-year follow-up of valve replacement with carbomedics valve.

BACKGROUND: The aim of this study was to report midterm valve replacement (VR) results with the Carbo-Medics valve (Sulzer Carbomedics, Austin, TX). METHODS: From 1991 to 1999, 468 patients aged 13 to 76 years (mean 56 years) underwent VR with CarboMedics valve: 239 aortic (A), 167 mitral (M), and 62 A+M or double valve replacement (DVR). Mean follow-up time was 4.4 years; follow-up was 99.1% complete for 2,016 patient-years (PY). The anticoagulation level was targeted to an international normalized ratio of 1.47 to 2.8. RESULTS: The hospital mortality rate was 1.2%. Actuarial analysis for the entire group at 7 years for survival was 87%+/-2.3%. Freedom from valve-related death was 94%+/-1.9%. Freedom from thromboembolic and bleeding events, respectively, were as follows: for AVR, 82%+/-4.9% (2.4%/PY) and 88%+/-2.9% (1.6%/PY); for MVR, 95%+/-2.1% (0.8%/PY) and 91%+/-3.1% (1.3%/PY); and for DVR, 96%+/-3.2% (0.7%/PY) and 85%+/-9.7% (1.0%/PY). Actuarial freedom from reoperation was 98%+/-1.4%. CONCLUSIONS: The CarboMedics valve can be implanted with satisfactory early mortality and a low incidence of valve-related events even under low-intensity anticoagulation, as shown in a Japanese population.

The effects of amiloride on the labellar taste receptor cells of the fleshfly Boettcherisca peregrina.

Amiloride is known to inhibit the taste response of vertebrates to salt by blocking the amiloride-sensitive sodium channel. In this study, we investigated electrophysiologically the effect of amiloride on the taste response of the fleshfly Boettcherisca peregrina. When 0.5 mM amiloride was included in taste solutions, the response of the salt receptor cell (salt response) to sodium chloride (NaCl) was not depressed but those of the sugar receptor cell (sugar responses) to sucrose, glucose, fructose, L-valine (L-Val) and L-phenylalanine (L-Phe) were strongly depressed. An inhibitory effect of amiloride on the concentration-response relationship for both sucrose and L-Phe was clearly revealed, but not at high concentrations of sucrose. After pretreatment of a chemosensory seta with 0.15 mM amiloride for 10 min, the salt response to NaCl was not affected. On the other hand, the sugar responses to sucrose, fructose, L-Val and L-Phe were depressed just after amiloride pretreatment. The sugar response to adenosine 5'-diphosphate (ADP) mixed with 0.5 mM amiloride was not depressed, but the response to ADP alone was depressed after amiloride pretreatment. It was therefore observed that amiloride depressed the responses to all stimulants that react with each of the receptor sites of the sugar receptor cell.