8 research outputs found
Solution structures of the DNA-binding domains of immune-related zinc-finger protein ZFAT
Oral angiotensin-converting enzyme inhibitor captopril protects the heart from Porphyromonas gingivalis LPS-induced cardiac dysfunction in mice
Vidarabine, an anti-herpes agent, improves Porphyromonas gingivalis lipopolysaccharide-induced cardiac dysfunction in mice
Abstract In this work, we examined the involvement of type 5 adenylyl cyclase (AC5) in cardiac dysfunction induced in mice given Porphyromonas gingivalis lipopolysaccharide (PG-LPS) at a dose equivalent to the circulating levels in periodontitis (PD) patients. Cardiac function was significantly decreased in mice given PG-LPS compared to the control, but treatment for 1Â week with the AC5 inhibitor vidarabine ameliorated the dysfunction. Cardiac fibrosis and myocyte apoptosis were significantly increased in the PG-LPS group, but vidarabine blocked these changes. The PG-LPS-induced cardiac dysfunction was associated with activation of cyclic AMP/Ca2+-calmodulin-dependent protein kinase II signaling and increased phospholamban phosphorylation at threonine 17. These results suggest that pharmacological AC5 inhibition may be a promising approach to treat PD-associated cardiovascular disease
Production of a Light-Gated Proton Channel by Replacing the Retinal Chromophore with Its Synthetic Vinylene Derivative
Rhodopsin is widely
distributed in organisms as a membrane-embedded
photoreceptor protein, consisting of the apoprotein opsin and vitamin-A
aldehyde retinal, A1-retinal and A2-retinal being the natural chromophores.
Modifications of opsin (e.g., by mutations) have provided insight
into the molecular mechanism of the light-induced functions of rhodopsins
as well as providing tools in chemical biology to control cellular
activity by light. Instead of the apoprotein opsin, in this study,
we focused on the retinal chromophore and synthesized three vinylene
derivatives of A2-retinal. One of them, C(14)-vinylene A2-retinal
(14V-A2), was successfully incorporated into the opsin of a light-driven
proton pump archaerhodopsin-3 (AR3). Electrophysiological experiments
revealed that the opsin of AR3 (archaeopsin3, AO3) with 14V-A2 functions
as a light-gated proton channel. The engineered proton channel showed
characteristic photochemical properties, which are significantly different
from those of AR3. Thus, we successfully produced a proton channel
by replacing the chromophore of AR3
Human T-cell receptor TCRAV, TCRBV, and TCRAJ sequences newly found in T-cell clones reactive with allogeneic HLA class II antigens
Human T-cell receptor TCRAV, TCRBV, and TCRAJ sequences newly found in T-cell clones reactive with allogeneic HLA class II antigens
National trends in the outcomes of subarachnoid haemorrhage and the prognostic influence of stroke centre capability in Japan: retrospective cohort study
Objectives To examine the national, 6-year trends in in-hospital clinical outcomes of patients with subarachnoid haemorrhage (SAH) who underwent clipping or coiling and the prognostic influence of temporal trends in the Comprehensive Stroke Center (CSC) capabilities on patient outcomes in Japan.Design Retrospective study.Setting Six hundred and thirty-one primary care institutions in Japan.Participants Forty-five thousand and eleven patients with SAH who were urgently hospitalised, identified using the J-ASPECT Diagnosis Procedure Combination database.Primary and secondary outcome measures Annual number of patients with SAH who remained untreated, or who received clipping or coiling, in-hospital mortality and poor functional outcomes (modified Rankin Scale: 3–6) at discharge. Each CSC was assessed using a validated scoring system (CSC score: 1–25 points).Results In the overall cohort, in-hospital mortality decreased (year for trend, OR (95% CI): 0.97 (0.96 to 0.99)), while the proportion of poor functional outcomes remained unchanged (1.00 (0.98 to 1.02)). The proportion of patients who underwent clipping gradually decreased from 46.6% to 38.5%, while that of those who received coiling and those left untreated gradually increased from 16.9% to 22.6% and 35.4% to 38%, respectively. In-hospital mortality of coiled (0.94 (0.89 to 0.98)) and untreated (0.93 (0.90 to 0.96)) patients decreased, whereas that of clipped patients remained stable. CSC score improvement was associated with increased use of coiling (per 1-point increase, 1.14 (1.08 to 1.20)) but not with short-term patient outcomes regardless of treatment modality.Conclusions The 6-year trends indicated lower in-hospital mortality for patients with SAH (attributable to better outcomes), increased use of coiling and multidisciplinary care for untreated patients. Further increasing CSC capabilities may improve overall outcomes, mainly by increasing the use of coiling. Additional studies are necessary to determine the effect of confounders such as aneurysm complexity on outcomes of clipped patients in the modern endovascular era