Background. Accelerated burst of polymorphonuclear leukocytes (PMNs) may be involved in the primary pathology of enhanced oxidative stress in patients with chronic kidney disease (CKD); however, the ...precise mechanism remains unknown. Methylglyoxal (MGO), an α-oxoaldehyde reportedly elevated in CKD, could induce apoptosis in several cell lines, and generates radicals by the reaction with hydrogen peroxide (H2O2). Thus, we tested if a high MGO of uraemic milieu could play a role in PMN injury by interaction with H2O2. Method. Cellular viability of PMNs, isolated from healthy volunteers, was tested by ATP chemiluminescence levels under MGO and/or H2O2, or 4-β phorbol 12-β-myristate 13-α-acetate (PMA). Superoxide anion (O2−) generation and apoptosis were measured by the reduction of ferricytochrome C and fluorocytometric analysis, respectively. Plasma MGO levels were measured by mass spectometry in 29 CKD patients. Results. At low levels of MGO (1–10 μM) and H2O2 (12.5 μM), no differences were found in cellular viability as compared to controls, whereas their combination significantly decreased PMN viability. PMA stimulation enhanced cellular injury of MGO by a function of MGO levels and preincubation with 5,5-dimethyl-1-pyrroline-N-oxide (free radical trap agent) attenuated it. MGO suppressed O2− generation by PMA, while it accelerated apoptotic ratios in PMNs. Significant increases of plasma MGO and C-reactive protein levels were found by a function of CKD stage, and clinical level of MGO could induce PMN injury in combination with H2O2. Conclusion. These results indicate the combinatory effect of MGO and H2O2 on PMN oxidative injury, and this pathology may be linked to enhanced oxidative stress in CKD.
We present novel results on the free base 5,10,15,20-meso-tetra(pyridyl)-21H,23H-porphyrin (H2TPyP). This molecule presents complex electronic and vibrational properties and despite the vast ...literature reporting the transitions observed in its absorption and fluorescence spectra, a more accurate interpretation has been kept elusive. In particular, we show that the molecule's Q-band develops into many electronic and vibronic transitions, whose the well-known “four orbital model” finds it difficult to reconcile. Using distinct spectroscopy techniques, we conclude that both Qx- and Qy-bands comprise, in fact, two quasi-degenerated electronic states together with their respective vibronic progressions each. The analysis of the Huang-Rhys factors and complementary time- and polarization-resolved measurements reinforce the need for the proposed Q-band multi features remodeling.
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•The asymmetric shape of Qy and Qx absorption bands of H2TPyP is discussed.•Q-band is composed of multi-electronic transitions.•Spectral derivative and deconvolution support remodeling of current description.•The vibrational modes belonging to vibronic progressions are determined.
The pion branching ratio,
R
π
=
Γ
(
π
+
→
e
+
ν
e
+
π
+
→
e
+
ν
e
γ
)
Γ
(
π
+
→
μ
+
ν
μ
+
π
+
→
μ
+
ν
μ
γ
)
, provides a sensitive test of lepton universality and constraints on many new physics ...scenarios. The theoretical uncertainty on the Standard Model prediction of
R
π
is 0.02 %, a factor of twenty smaller than the experimental uncertainty. The analysis of a subset of data taken by the PIENU experiment will be presented. The result,
R
π
= (1.2344 ± 0.0023(
s
t
a
t
) ± 0.0019(
s
y
s
t
)) ⋅ 10
−4
1
, is consistent with the Standard Model prediction and represents a 0.1 % constraint on lepton non-universality.
We retrospectively analyzed our results of 30 patients with three distinctive primary immunodeficiency diseases (PIDs)--severe combined immunodeficiency (SCID, n = 11), Wiskott-Aldrich syndrome (WAS, ...n = 11) and X-linked hyper-immunoglobulin M (IgM) syndrome (XHIM, n = 8)--who underwent hematopoietic SCT (HSCT) during the past 20 years. Until 1995, all donors were HLA-haploidentical relatives with T-cell depletion (TCD) (n = 8). Since 1996, the donors have been HLA-matched related donors (MRD) (n = 8), unrelated BM (UR-BM) (n = 7) and unrelated cord blood (UR-CB) (n = 7). Twenty-seven of 30 patients had various pre-existing infections with or without organ damages before HSCT. Conditioning regimen and GVHD prophylaxis were determined according to disease, donor and pretransplant status. Although one of eight patients transplanted with TCD is alive with full engraftment, the other seven died. On the other hand, 18 of 22 patients transplanted without TCD are alive and well, including six of eight transplanted from MRD, seven of seven from UR-BM and five of seven from UR-CB. All 19 survivors did not require Ig supplementation after HSCT. These results indicate that UR-CBT as well as UR-BMT provides good results for PID comparable to MRD-SCT, and that early diagnosis, HSCT at early stage, careful supportive therapy and monitoring for various pathogens are important for the successful HSCT.
A hyphomycete consistently isolated from dead oak trees (Quercus serrata and Q. mongolica var. grosseserrata) attacked by the ambrosia beetle Platypus quercivorus in Japan is described and ...illustrated as Raffaelea quercivora sp. nov. The new species is characterized by having small obovoid to pyriform sympodioconidia and slender, long conidiophores that taper to a point. The fungus has been isolated from the body surfaces and mycangia of the beetle. It is likely that the fungus was transferred to oak trees by P. quercivorus.
Anti-glucose-6-phosphate isomerase (GPI) antibodies from K/BxN mice directly induce arthritis; however, the transfer of these antibodies from mice with GPI-induced arthritis does not induce ...arthritis. CD4⁺ T cells play an important role in the induction and effector phase in this model; however, the roles of B cells and immunoglobulins (Igs) have not been elucidated. We investigated the roles of B cells and Igs in GPI-induced arthritis by using adoptive transfer system into SCID mice. Transfer of splenocytes of male DBA/1 mice immunized with GPI into SCID mice induced arthritis on day 6 in the latter, in association with the production of anti-GPI antibodies. Co-localization of C3 and IgG on the articular surface was identified in arthritic SCID mice. Inoculation of IgG (or anti-GPI antibodies) and CD19⁺-depleted splenocytes from arthritic DBA/1 mice induced arthritis in SCID mice, but not CD19⁺-depleted or CD4⁺-depleted splenocytes from DBA/1 mice. In vitro analysis of cytokine production by splenocytes from DBA/1 arthritic mice demonstrated production of large amounts of tumour necrosis factor (TNF)-α and interleukin (IL)-6 in an antigen-specific manner (P < 0·01), and production was dominated by CD19⁺-depleted than CD4⁺-depleted splenocytes (P < 0·05). Addition of IgG from DBA/1 arthritic mice to the culture enhanced TNF-α but not IL-6 production, and this effect was blocked by anti-Fcγ receptor antibody. In vivo analysis of neutralization with TNF-α protected arthritis completely in SCID mice. Our results highlight the important role of B cells in GPI-induced arthritis as autoantibody producers, and these autoantibodies can trigger joint inflammation in orchestration with inflammatory cytokines, especially TNF-α.
Abstract Although neuromedin U (NMU) and neuromedin S (NMS) are reported to modulate stress responses mainly through corticotropin-releasing hormone system in rodents, the in vivo effects of ...centrally administered NMU or NMS on stress regulation have not been fully elucidated in cattle. We examined adrenocorticotropic hormone levels, body temperature, and behavioral responses to intracerebroventricularly (ICV) administered rat NMU or rat NMS in steers. ICV NMU and NMS (0.2, 2, and 20 nmol/200 μl) evoked a dose-related increase in plasma cortisol concentrations (CORT). There was a significant time–treatment interaction for the time course of CORT ( p < 0.001). ICV NMU evoked a dose-related increase in rectal temperature (RT). There was a significant time–treatment interaction for the change in RT from pre-injection value ( p < 0.05). There was a significant difference among treatments in the percentage of time spent lying (Friedman’s test, χ2 = 15.6, p < 0.01) and in the total number of head shaking (Friedman’s test, χ2 = 14.49, p < 0.01). A high dose of NMS tended to shorten the duration of lying and increase the number of head shaking. These findings indicate that both central NMU and NMS might participate in controlling the hypothalamo–pituitary–adrenal axis, that central NMU might participate in controlling body temperature, and that central NMS is likely to be involved in behavioral activation in cattle.
Summary
Aim
To conduct a retrospective multicentre study at 31 medical centres in Japan, to investigate the association between the eradication of Helicobacter pylori and the development of new ...gastric cancer after endoscopic mucosal resection (EMR) for early gastric cancer.
Methods
Patients included those in whom early gastric cancer had been removed by EMR, and who had received follow‐up endoscopic treatment. All patients underwent follow‐up endoscopic treatment at least once a year after the initial EMR. The rate of new gastric cancer development was compared among those patients for whom H. pylori had been successfully eradicated and those with persistent H. pylori infection.
Results
The study included 2835 patients with a median follow‐up period of 2 years (range 0.5–12 years). Helicobacter pylori was eradicated in 356 patients (13%). Metachronous gastric cancers developed in eight (2%) patients among those who had been successfully treated for H. pylori, compared with 129 patients (5%) among those with persistent H. pylori infection (P = 0.021; OR = 0.42; 95% CI = 0.20–0.86).
Conclusion
Although longer term, prospective randomized controlled trials are needed to better estimate the extent and sustainability of possible benefits, this study suggests that the eradication of H. pylori may help reduce the incidence of metachronous gastric cancer.
Abstract We characterized bradykinin (BK)-induced changes in the intracellular Ca2+ concentration (Ca2+ i) and membrane potential in cultured rat myenteric neurons using ratiometric Ca2+ imaging with ...fura-2 and the whole-cell patch-clamp technique, respectively. BK evoked a dose-dependent increase of Ca2+ i that was abolished by HOE 140, a B2 receptor antagonist but not by Lys-des-Arg9 -BK, a B1 receptor antagonist. Lys-des-Arg9 -HOE140, a B1 receptor agonist, failed to cause a Ca2+ i response. Double staining with antibodies against the B2 receptor together with PGP9.5 or S100 indicated that B2 receptors were expressed in neurons and glial cells. The BK-evoked Ca2+ i increase was suppressed by indomethacin, a non-selective cyclooxygenase (COX) inhibitor, and potentiated by prostaglandin E2 (PGE2 ). The release of PGE2 from cultured myenteric plexus cells was increased by BK. BK induced a large increase in Ca2+ i in neurons when myenteric plexus cells were cultured at the high density but not at the low density, and caused a small increase in Ca2+ i in neurons when proliferation of enteric glial cells was suppressed. BK evoked a slow and sustained depolarization in myenteric neurons, which was sensitive to indomethacin. These results indicated that BK caused a Ca2+ i increase and depolarization in rat myenteric neurons through the activation of B2 receptors, which was partly associated with PGE2 released from glial cells in response to BK. It is suggested that a neuron–glial interaction plays an important role in the effect of BK in the rat myenteric plexus.
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