Gramicidin-perforated Patch Recording Revealed the Oscillatory Nature of Secretory Cl− Movements in Salivary Acinar Cells

Elevations of cytoplasmic free calcium concentrations ([Ca2+]i) evoked by cholinergic agonists stimulate isotonic fluid secretion in salivary acinar cells. This process is driven by the apical exit of Cl− through Ca2+-activated Cl− channels, while Cl− enters the cytoplasm against its electrochemical gradient via a loop diuretic-sensitive Na+-K+-2Cl− cotransporter (NKCC) and/or parallel operations of Cl−-HCO3− and Na+-H+ exchangers, located in the basolateral membrane. To characterize the contributions of those activities to net Cl− secretion, we analyzed carbachol (CCh)-activated Cl− currents in submandibular acinar cells using the “gramicidin-perforated patch recording configuration.” Since the linear polypeptide antibiotic gramicidin creates monovalent cation-selective pores, CCh-activated Cl− currents in the gramicidin-perforated patch recording were carried by Cl− efflux via Cl− channels, dependent upon Cl− entry through Cl− transporters expressed in the acinar cells. CCh-evoked oscillatory Cl− currents were associated with oscillations of membrane potential. Bumetanide, a loop diuretic, decreased the CCh-activated Cl− currents and hyperpolarized the membrane potential. In contrast, neither methazolamide, a carbonic anhydrase inhibitor, nor elimination of external HCO3− had significant effects, suggesting that the cotransporter rather than parallel operations of Cl−-HCO3− and Na+-H+ exchangers is the primary Cl− uptake pathway. Pharmacological manipulation of the activities of the Ca2+-activated Cl− channel and the NKCC revealed that the NKCC plays a substantial role in determining the amplitude of oscillatory Cl− currents, while adjusting to the rate imposed by the Ca2+-activated Cl− channel, in the gramicidin-perforated patch configuration. By concerting with and being controlled by the cation steps, the oscillatory form of secretory Cl− movements may effectively provide a driving force for fluid secretion in intact acinar cells

Abdominal obesity exhibits distinct effect on inflammatory and anti-inflammatory proteins in apparently healthy Japanese men

<p>Abstract</p> <p>Background</p> <p>Since visceral fat tissue is known to release various inflammatory and anti-inflammatory cytokines, abdominal obesity may play a key role in the inflammation associated with metabolic syndrome (MetS). However, few studies have determined precise relationships of abdominal obesity with inflammatory markers in MetS. To clarify the importance of abdominal obesity in sub-clinical inflammation, we examined the changes of inflammatory markers in clustering of MetS components with or without abdominal obesity.</p> <p>Methods</p> <p>Subjects consisted of 326 apparently healthy Japanese men (age: 30 to 59 years) who underwent health examination in the Osaka University Health Care Center. MetS components were assessed and serum levels of high sensitive C-reactive protein (hs-CRP), interleukin (IL)-6 and adiponectin were examined in all subjects.</p> <p>Results</p> <p>Subjects with abdominal obesity (waist circumference ≥ 85 cm) showed higher serum hs-CRP and IL-6 levels and a lower adiponectin level than those without abdominal obesity. Serum levels of hs-CRP and IL-6 significantly increased in association with clustering of MetS components in the subjects with abdominal obesity, but not in those without abdominal obesity. On the other hand, serum adiponectin level exhibited a little change with clustering of MetS components in the subjects with abdominal obesity. Significant negative correlation between adiponectin and hs-CRP was observed in the subjects with abdominal obesity, however this correlation was not detected in obese subjects defined by body mass index ≥ 25.</p> <p>Conclusion</p> <p>Inflammatory status is not exaggerated by clustering of MetS components in the subjects without abdominal obesity. Abdominal obesity may exhibit distinct effect on inflammatory and anti-inflammatory proteins and modulate inflammatory network in MetS.</p

Spectral Evolutions in Gamma-Ray Burst Exponential Decays Observed with Suzaku WAM

This paper presents a study on the spectral evolution of gamma-ray burst (GRB) prompt emissions observed with the Suzaku Wide-band All-sky Monitor (WAM). By making use of the WAM data archive, 6 bright GRBs exhibiting 7 well-separated fast-rise-exponential-decay (FRED) shaped light curves are presented and the evaluated exponential decay time constants of the energy-resolved light curves from these FRED peak light curves are shown to indicate significant spectral evolution. The energy dependence of the time constants is well described with a power-law function tau(E) ~ E^gamma, where gamma ~ -(0.34 +/- 0.12) in average, although 5 FRED peaks show consistent value of gamma = -1/2 which is expected in synchrotron or inverse-Compton cooling models. In particular, 2 of the GRBs were located with accuracy sufficient to evaluate the time-resolved spectra with precise energy response matrices. Their behavior in spectral evolution suggests two different origins of emissions. In the case of GRB081224, the derived 1-s time-resolved spectra are well described by a blackbody radiation model with a power-law component. The derived behavior of cooling is consistent with that expected from radiative cooling or expansion of the emission region. On the other hand, the other 1-s time-resolved spectra from GRB100707A is well described by a Band GRB model as well as with the thermal model. Although relative poor statistics prevent us to conclude, the energy dependence in decaying light curve is consistent with that expected in the former emission mechanism model.Comment: 11 pages, 7 figures, 5 tables. PASJ accepte

Spectral evolution of GRB 060904A observed with Swift and Suzaku -- Possibility of Inefficient Electron Acceleration

We observed an X-ray afterglow of GRB 060904A with the Swift and Suzaku satellites. We found rapid spectral softening during both the prompt tail phase and the decline phase of an X-ray flare in the BAT and XRT data. The observed spectra were fit by power-law photon indices which rapidly changed from $\Gamma = 1.51^{+0.04}_{-0.03}$ to $\Gamma = 5.30^{+0.69}_{-0.59}$ within a few hundred seconds in the prompt tail. This is one of the steepest X-ray spectra ever observed, making it quite difficult to explain by simple electron acceleration and synchrotron radiation. Then, we applied an alternative spectral fitting using a broken power-law with exponential cutoff (BPEC) model. It is valid to consider the situation that the cutoff energy is equivalent to the synchrotron frequency of the maximum energy electrons in their energy distribution. Since the spectral cutoff appears in the soft X-ray band, we conclude the electron acceleration has been inefficient in the internal shocks of GRB 060904A. These cutoff spectra suddenly disappeared at the transition time from the prompt tail phase to the shallow decay one. After that, typical afterglow spectra with the photon indices of 2.0 are continuously and preciously monitored by both XRT and Suzaku/XIS up to 1 day since the burst trigger time. We could successfully trace the temporal history of two characteristic break energies (peak energy and cutoff energy) and they show the time dependence of $\propto t^{-3} \sim t^{-4}$ while the following afterglow spectra are quite stable. This fact indicates that the emitting material of prompt tail is due to completely different dynamics from the shallow decay component. Therefore we conclude the emission sites of two distinct phenomena obviously differ from each other.Comment: 19 pages, 9 figures, accepted for publication in PASJ (Suzaku 2nd Special Issue

Pemphigus vulgaris as an immune-related adverse event in recurrent metastatic esophageal squamous cell carcinoma treated with ipilimumab plus nivolumab: a case report and literature review

Ipilimumab plus nivolumab therapy is approved for patients with unresectable advanced esophageal squamous cell carcinoma (ESCC). Although a combination of immune checkpoint inhibitors (ICIs), compared to conventional chemotherapy, can improve overall survival in patients with advanced ESCC, this increases the incidence of immune-related adverse events (irAEs). Here, we describe an ESCC case that developed pemphigus vulgaris (PV), an extremely rare cutaneous irAE, during ipilimumab plus nivolumab treatment. The patient achieved a partial response to treatment. The PV was successfully managed after the cessation of ipilimumab and the use of a topical steroid. We should thus re-treat ESCC with nivolumab monotherapy. In the era of ICIs as standard cancer therapeutics, diagnostic criteria for blistering diseases need to be established to properly manage patients with cutaneous irAEs

Reviewing E(sub peak) Relations with Swift and Suzaku Data

In recent years several authors have derived correlations between gamma-ray burst (GRB) spectral peak energy (E(sub peak)) and either isotropic-equivalent radiated energy (E(sub iso)) or peak luminosity (L(sub iso)). Since these relationships are controversial, but could provide redshift estimators, it is important to determine whether bursts detected by Swift exhibit the same correlations. Swift has greatly added to the number of GRBs for which redshifts are known and hence E(sub iso) and L(sub iso) could be calculated. However, for most bursts it is not possible to adequately constrain E(sub peak) with Swift data alone since most GRBs have E(sub peak) above the energy range (15-50 keV) of the Swift Burst Alert Telescope (BAT). Therefore we have analyzed the spectra of 78 bursts (31 with redshift) which were detected by both Swift/BAT and the Suzaku Wide-band All-sky Monitor (WAM), which covers the energy range 50-5000 keV. For most bursts in this sample we can precisely determine E(sub peak) and for bursts with known redshift we can compare how the E(sub peak) relations for the Swift/Suzaku sample compare to earlier published results. Keywords: gamma rays: burst