A nearby transiting rocky exoplanet that is suitable for atmospheric investigation.

Spectroscopy of transiting exoplanets can be used to investigate their atmospheric properties and habitability. Combining radial velocity (RV) and transit data provides additional information on exoplanet physical properties. We detect a transiting rocky planet with an orbital period of 1.467 days around the nearby red dwarf star Gliese 486. The planet Gliese 486 b is 2.81 Earth masses and 1.31 Earth radii, with uncertainties of 5%, as determined from RV data and photometric light curves. The host star is at a distance of ~8.1 parsecs, has a J-band magnitude of ~7.2, and is observable from both hemispheres of Earth. On the basis of these properties and the planet's short orbital period and high equilibrium temperature, we show that this terrestrial planet is suitable for emission and transit spectroscopy.

Snapping pes syndrome after total knee arthroplasty.

Snapping syndrome rarely occurs at the knee joint. This is the first report of snapping pes syndrome after total knee arthroplasty. Surgeons should be aware of the presence of such a case and pay attention to the fact that snapping symptoms could be caused by a residual bony prominence and a change in alignment after total knee arthroplasty.

Cytosine-phosphate-guanosine-DNA induces CD274 expression in human B cells and suppresses T helper type 2 cytokine production in pollen antigen-stimulated CD4-positive cells.

Co-stimulatory molecules are important for regulating T cell activation and immune response. CD274 [programmed death ligand 1 (PD-L1), B7-H1] has emerged as an important immune modulator that can block T cell receptor signalling. We have investigated whether PD-L1 and other co-stimulatory ligands could be expressed in human B cells stimulated by cytosine-phosphate-guanosine (CpG)-DNA. CpG-DNA strongly induced the co-inhibitory molecule ligand, PD-L1, of human B cells. Results show that nuclear factor-kappa B (NF-κB) signalling is involved directly in CpG-DNA-induced PD-L1 expression in human B cells. We sought to determine the effect of CpG-DNA-treated B cells on T helper type 2 (Th2) cytokine production in Cry j 1 (Japanese pollen antigen)-stimulated human CD4-positive cells from patients with seasonal allergic rhinitis caused by Japanese cedar pollen. CpG-DNA-treated B cells reduced Cry j 1-induced interleukin (IL)-5 and IL-13 production in CD4-positive cells. When the binding of PD-1 to PD-L1 was inhibited by PD-1-immunoglobulin (Ig), this chimera molecule reversed the previously described reductions in IL-5 and IL-13 production. In contrast, the CpG B-treated B cells increased both interferon (IFN)-γ and IL-12 production in the presence of Cry j 1-stimulated CD4-positive cells. CpG-DNA simultaneously reduced the expression of B7RP-1 [also known as inducible co-stimulator ligand (ICOSL), B7-H2] and the ligand of CD30 (CD30L). These results indicate that CpG-DNA induces co-inhibitory molecule ligand PD-L1 expression in human B cells and PD-L1 can suppress Th2 cytokine production in Cry j 1-stimulated CD4-positive cells, while CpG-DNA increased Th1 cytokine production and reduced the expression of co-stimulatory molecule ligands that can promote Th2 inflammatory responses.

Systemic pregabalin attenuates sensorimotor responses and medullary glutamate release in inflammatory tooth pain model.

Our previous studies have demonstrated that application of inflammatory irritant mustard oil (MO) to the tooth pulp induces medullary glutamate release and central sensitization in the rat medullary dorsal horn (MDH), as well as nociceptive sensorimotor responses in craniofacial muscles in rats. There is recent evidence that anticonvulsant drugs such as pregabalin that influence glutamatergic neurotransmission are effective in several pain states. The aim of this study was to examine whether systemic administration of pregabalin attenuated glutamate release in the medulla as well as these nociceptive effects reflected in increased electromyographic (EMG) activity induced by MO application to the tooth pulp. Male adult rats were anesthetized with isofluorane (1.0-1.2%), and jaw and tongue muscle EMG activities were recorded by needle electrodes inserted bilaterally into masseter and anterior digastric muscles and into the genioglossus muscle, and also the medullary release of glutamate was assessed by in vivo microdialysis. Pregabalin or vehicle control (isotonic saline) was administered 30 min before the pulpal application of MO or vehicle control (mineral oil). Application of mineral oil to the maxillary first molar tooth pulp produced no change in baseline EMG activity and glutamate release. However, application of MO to the pulp significantly increased both the medullary release of glutamate and EMG activity in the jaw and tongue muscles for several minutes. In contrast, pre-medication with pregabalin, but not vehicle control, significantly and dose-dependently attenuated the medullary glutamate release and EMG activity in these muscles after MO application to the tooth pulp (analysis of variance (ANOVA), p<0.05). These results suggest that pregabalin may attenuate the medullary release of glutamate and associated nociceptive sensorimotor responses in this acute inflammatory pulpal pain model, and that it may prove useful for the treatment of orofacial inflammatory pain states.

Influence of beverage and food consumption on fluoride intake in Japanese children aged 3-5 years.

This study was conducted to estimate the relative contribution of particular foods and drinks to dietary fluoride intake in 94 preschool Japanese children in low-fluoride areas. The mean daily fluoride intake from all beverages (548 +/- 162 g) was 0.108 mg (SD = 0.082), accounting for 37% of the total dietary fluoride; tea beverages showed the highest value, 0.093 mg (SD = 0.081), 32%. That from staple food and side dishes was 0.183 mg (SD = 0.146), 63%, followed by cereals (12%), fish (8%) and bean products (5%). In conclusion, the contribution of beverages excluding tea to dietary fluoride intake is small in Japanese children.

Functional RET G691S polymorphism in cutaneous malignant melanoma.

RET proto-oncogene encodes a receptor tyrosine kinase whose ligand is glial cell line-derived neurotrophic factor (GDNF), and its polymorphism at G691S juxtamembrane region (RETp) is a germline polymorphism. Cutaneous melanomas, particularly the desmoplastic subtype, are highly neurotropic; thus we sought to determine the frequency of RETp in cutaneous melanoma and its functional responsiveness to GDNF. RETp was assessed in 71 non-desmoplastic cutaneous melanomas (non-DMs) and 70 desmoplastic melanomas (DMs). Melanoma cell lines with RETp, RET wild type (RETwt), BRAF V600E mutation (BRAFmt) or BRAF wild type (BRAFwt) were assessed for functional activity. RETp frequency was significantly higher in DMs (61%) than in non-DMs (31%, P<0.001). BRAFmt was detected in only 11% of DMs. GDNF stimulation significantly amplified cell proliferation, migration and invasion in RETp, but not in RETwt melanoma cells. GDNF stimulation of RETp cell lines enhanced phosphorylation of extracellular signal-regulated kinase (ERK) and Akt of the RET-RAS-RAF-ERK and RET-phosphatidylinositol 3-kinase (PI3K)-Akt pathways, respectively. GDNF response of RETp cells in signal transduction and other functional studies were not affected by BRAFmt. The study demonstrates that RETp is frequently found in cutaneous melanoma, particularly desmoplastic subtypes, and responds to GDNF inducing events favorable for tumor progression.

Fluoride intake in Japanese children aged 3-5 years by the duplicate-diet technique.

This study was conducted to determine the fluoride intakes in 94 preschool children aged 3, 4 and 5 (n = 30, 30, 34, respectively) residing in Yokkaichi, Mie Prefecture (< 0.16 ppm F water supply). The parents duplicated all the diets that their children ingested on 3 separate days during a 1-year period. The acid-diffusible fluoride in the diet was isolated by the acid-diffusion technique and measured with a fluoride electrode. The mean daily fluoride intakes from diet alone by children aged 3, 4 and 5 were 0.30 mg (n = 29, SD 0.19), 0.28 mg (n = 30, SD 0.19) and 0.30 mg (n = 34, SD 0.19), respectively. The total estimated mean values from diet and dentifrice were 0.35 mg (n = 29, SD 0.22, range 0.13-1.00), 0.33 mg (n = 30, SD 0.19, range 0.13-0.86) and 0.39 mg (n = 34, SD 0.18, range 0.18-1.01), respectively. It was concluded that the mean (+/-SD) total fluoride from diet and dentifrice in 3- to 5-year-old Japanese children was 0.35 +/- 0.19 mg/day (0.021 +/- 0.012 mg/kg body weight).

A serotonin malfunction hypothesis by finding clear mutual relationships between several risk factors and symptoms associated with sudden infant death syndrome.

In our recent study allele variants in the promoter of serotonin transporter (5-HTT) gene have been shown as a novel risk factor for sudden infant death syndrome (SIDS). L and XL alleles were more frequent and S allele was less frequent in SIDS victims compared to age-matched controls. Serotonin (5-HT) is suggested as a major agent that is closely involved in the etiology of SIDS. Although many risk factors of SIDS looked mutually unrelated each other, we found in literature many of them other than prone position to change 5-HT levels in the brain. Along with the genetic factors, environmental and temporal factors appear additively to lower the excitatory function of 5-HT to the respiratory center, and finally SIDS might occur. Now the pathophysiological mechanisms and symptoms of SIDS are explained by decreased levels of 5-HT.

Transcription factors GATA-4 and GATA-6 during mouse and human adrenocortical development.

Our earlier work implicates transcription factors GATA-4 and GATA-6 in the murine adrenal. We have now studied their expression during mouse and human adrenal development in detail. GATA-4 and GATA-6 mRNAs are readily detectable from embryonic day 15 in mouse and gestational week 19 in human adrenal cortex. In postnatal adrenal, GATA-4 expression is down-regulated, whereas GATA-6 mRNA and protein continue to be abundantly present. In a human adrenocortical cell line NCI-H295R, GATA-6 mRNA is up-regulated by cAMP. This cell line does not express GATA-4. Our findings suggest that GATA-6 expression is hormonally controlled, and required throughout adrenal development from fetal to adult age. GATA-4, on the other hand, may serve a role in fetal adrenal gene regulation.

A biogenic amine-synapse mechanism for mental retardation and developmental disabilities.

Recent studies have demonstrated that biogenic amines have a function of facilitating formation and maintenance of synapses in diverse regions of the central nervous system in developing and adult animals. The normal number of synapses maintained by biogenic amines are crucial to acquire learning and memory. The level of biogenic amines was reported to decrease in the brain by several neurodevelopmental disorders associated with mental retardation and developmental disabilities such as Rett syndrome, autism and Down syndrome. Taken into consideration this fact together with the function of biogenic amines for synapses, the density of synapses appears to decrease considerably in the brains of patients suffered from the neurodevelopmental disorders. The synaptic overproduction during the critical period of development especially 1 year after birth has been considered as a background mechanism to provide plasticity for the developing brain. Synaptic overproduction does not appear to occur in the brains of patients suffered from the neurodevelopmental disorders, which they are observed mental retardation occurring in the first 1 year after birth. Along with the neurodevelopmental disorders, environmental factors (stress, drugs and nutrition) during pre- and post-natal critical developmental periods are known to change levels of biogenic amines in the brain. In fact, maternal stress has been shown to decrease the levels of serotonin and the density of synapses in the hippocampus of the offspring, and they showed developmental disabilities in the spatial learning and memory. A cascade appears to exist from either the child neurological disorders or the environmental factors to mental retardation and developmental disabilities by decreases in the levels of biogenic amines and synaptic density.

[Acute exacerbations due to Streptococcus pneumoniae in chronic lower respiratory tract infections during long-term macrolide therapy].

In Japan, long-term 14-membered macrolide administration is chosen as a first line therapy against chronic lower respiratory tract infections (CLRTIs) such as diffuse panbronchiolitis, bronchiectasis and chronic bronchitis. However, sometimes acute exacerbations occur in these cases, even if therapy is effective. We investigated 18 episodes of CLRTIs exacerbations that were caused by Streptococcus pneumoniae during long-term macrolides therapy from 1991 to 1999 to clarify the clinical features and prevalence of antimicrobial resistance in S. pneumoniae. Exacerbations did not occur only in winter season, but also in other seasons. Among 18 episodes of exacerbation, only 7 episodes (39%) revealed infiltration in chest roentogenogram and few episodes revealed marked elevations of inflammation markers in laboratory data. Intermediate resistance or resistance rates of S. pneumoniae isolated from sputum or transtracheal aspiration were 100% to erythromycin, 67% to clindamycin or minocycline, 11% to ampicillin, and 0% to cephazoline or imipenem. Coresistance to erythromycin, clindamycin and minocycline was seen in a half of the episodes. Resistance was not correlated with the duration of macrolides administration. All episodes were mainly treated with beta-lactam agents or fluoroquinolones and cured successfully. These findings suggest that acute exacerbations in CLRTIs caused by S. pneumoniae during long-term macrolides therapy do not reveal severe clinical aspects and can be treated successfully at present, but attention should be paid to the trend of antibiotic susceptibility in S. pneumoniae.

[Usefulness of three-dimensional color Doppler sonography for the differential diagnosis of subpleural lesions].

The purpose of our investigation was to assess the usefulness of three-dimensional color Doppler sonography (velocity mode and power mode) for the differential diagnosis of subpleural lesions. Thirty lesions (11 pneumonias, 5 lung abscesses, 11 primary lung cancers, 3 metastatic lung cancers) were examined. Three-dimensional images were reconstructed by a maximum intensity projection method. Three-dimensional representations of intralesional blood flow became available for all lesions approximately 11 seconds after scanning. In every case, the entire vasculature of the tumor, the pneumonia, the abscess, or the inflamed region of the lung was appreciated more easily from three-dimensional images than from two-dimensional images. We classified the color flow pattern of subpleural lesions depicted by color flow imaging into seven groups. Color flow was depicted better by the three-dimensional color Doppler power mode than the velocity mode. Three-dimensional color flow patterns observed in power mode, patterns of the pneumonias and the lung cancers differed significantly. Our results suggest that the three-dimensional color Doppler power mode is useful for the differential diagnosis of subpleural lesions.

[A study on relation between active pulmonary tuberculosis and underlying diseases].

A study was made on the relation between active pulmonary tuberculosis and underlying diseases in 119 tuberculosis patients. Out of total 119 patients, 87 patients (73.1%) had underlying diseases. The most common underlying disease was diabetes mellitus in 34 patients (39.1%), followed by HCV (+) chronic hepatitis, sequela of cerebral infarction, hypertension and gastric ulcer. In patients who had underlying diseases, the mean age was higher, proportion of sputum smear positive cases was higher, albumin was lower, and period until sputum culture negative conversion was longer. In patients who had diabetes mellitus, proportion of cases with cavity on chest X-P was higher, and in patients who had sequela of cerebral infarction or hypertension, mean age was higher. In patients who had diabetes mellitus and whose HbA1C was > or = 9%, proportion of smear positive cases was higher, albumin was lower and period until culture negative conversion was longer than in patients who had diabetes mellitus and whose HbA1c was < 9%, suggesting that control of blood sugar in diabetes mellitus related to severity of pulmonary tuberculosis. In patients who had diabetes mellitus and whose albumin was < 3 g/dl, period until culture negative conversion was longer than in patients who had diabetes mellitus and whose albumin was > or = 3 g/dl. In patients who had underlying diseases, these diseases caused decline of tuberculous immunity and nutritional disturbance represented by lower albumin also promoted decline of tuberculous immunity. It is suggested that the underlying diseases affected the onset and progression of pulmonary tuberculosis.

[Epidural blood patch for the treatment of intracranial hypotension due to cerebrospinal fluid leakage after thoracic spine surgery].

We report a case of a 44-year-old woman successfully treated by an epidural blood patch for intracranial hypotension due to cerebrospinal fluid (CSF) leakage into the thoracic cavity after thoracic spine surgery. The patient was admitted to our hospital with the complaint of postural headaches. She had received anterior thoracic instrumentation for thoracic disc herniation four months earlier. Lumbar puncture demonstrated low CSF pressure, and Gd-enhanced MR images displayed diffuse dural enhancement. Accordingly, she was diagnosed as having intracranial hypotension. 111In-DTPA cisternography revealed a CSF leakage into the left thoracic cavity, possibly caused by dural laceration during thoracic spine surgery. To avoid the risk of direct surgery, we performed epidural blood patch; 3 ml of autologous blood was injected into the epidural cavity. Postoperatively postural headaches immediately disappeared. MRI taken one year later revealed disappearance of diffuse dural enhancement, and 111In-DTPA cisternography revealed no CSF fluid leaks. Epidural blood patch seems to be a choice of treatment for CSF leak after spinal surgery.

Mechanisms of action of the novel sulfonamide anticancer agent E7070 on cell cycle progression in human non-small cell lung cancer cells.

E7070 is a novel sulfonamide antitumor agent that exhibits potent antitumor activity in vitro and in vivo. This compound affects cell cycle progression in human tumor cells. To elucidate the mechanisms by which E7070 inhibits tumor cell growth, we established and characterized an E7070-resistant subline, A549/ER, from a human non-small cell lung cancer cell line A549. Flow cytometric analyses demonstrated an increase in G0/G1 and a decrease in S phase populations in cells treated with E7070 at 20 or 100 microg/ml for 24 h. Longer exposure to E7070, i.e. 48 and 72 h, increased the G2/M phase fraction in A549 cells. These inhibitory actions of E7070 on cell cycle progression were not observed in A549/ER cells. E7070 inhibited the phosphorylation of pRb, decreased expressions of cyclin A, B1, CDK2, and CDC2 proteins, and suppressed CDK2 catalytic activity with the induction of p53 and p21 proteins in A549 cells but not in A549/ER cells. Taken together, these results suggest that E7070 exerts its antitumor effects by disturbing the cell cycle at multiple points, including both the G1/S and the G2/M transition, in human lung cancer cells.

The effect of nutritional status on morbidity in COPD patients undergoing bilateral lung reduction surgery.

BACKGROUND: Although candidates for lung reduction surgery (LRS) include malnourished patients with severe chronic obstructive pulmonary disease (COPD), the impact of preoperative nutritional status on surgical outcome has not been clearly elucidated. METHODS: We investigated the relationship between preoperative nutritional status and postoperative morbidity in 23 consecutive patients undergoing LRS. The percentage of ideal body weight (%IBW) and body mass index (BMI) were calculated, and fat-free mass (FFM) and fat mass (FM) were measured using a bioelectrical impedance analyzer. FFM and FM were expressed as height-normalized indices, FFM index [FFM (kg)/height (m)(2), or FFMI] and FM index [FM (kg)/height (m)(2), or FMI]. Serum levels of total protein and albumin were also determined. RESULTS: 8 patients had major complications. Preoperative %IBW and FFMI were significantly lower among patients with major complications, while no significant differences were observed in pulmonary function, FMI or serum protein. The complication rate was significantly higher among patients with low FFMI (FFMI < or = 16) but not with low %IBW or BMI. CONCLUSION: These results suggest that FFM depletion is an excellent predictor of unacceptable postoperative complication following LRS.

Enhanced low shear stress induced platelet aggregation by Shiga-like toxin 1 purified from Escherichia coli O157.

The effect of Shiga-like toxin 1 (Stx1) produced by Escherichia coli O157 on platelets was studied with an argon laser light-assisted shear-induced platelet aggregometer and with binding assays. Stx1 markedly enhanced the platelet aggregation under low shear stress but did not affect it under high shear stress. Minimal concentration of Stx1 required for the enhancement was 0.25 ng/ml, and almost maximal enhancement was observed at a final concentration of > or =2.5 ng/ml. This enhanced platelet aggregation disappeared after leukocyte depletion from normal platelet-rich plasma with a specific filter. In contrast, a standard platelet aggregometer was unable to detect this enhanced platelet aggregation in either the presence or the absence of ADP. 125I-labeled purified Stx1 did not specifically bind to normal washed platelets depleted of leukocytes, and thin-layer chromatographic analysis of glycolipids extracted from normal platelet lysates also confirmed that leukocyte-depleted normal platelets lack Stx1-specific receptor globotriaosylceramide (Gb3). Supernatant from the monocyte suspension stimulated with Stx1 exhibited the enhanced low shear stress induced platelet aggregation, but that from the polymorphonuclear cell suspension did not. Several cytokines produced from monocytes reproduced this event in vitro. Further, plasmas from six out of seven patients with hemolytic uremic syndrome (HUS) had activity similar to the purified Stx1. This activity was almost totally impaired after treatment of HUS plasmas with Gb3 in accord with reduction of plasma Stx1 levels. Taken together, these results indicate that platelets lack Gb3, and Stx1 appears to modulate platelet aggregation in an indirect fashion, presumably by the release of cytokines or chemical compounds from the target tissues.