Actin filaments-stabilizing and -bundling activities of cofilin-phosphatase Slingshot-1

Slingshot-1 (SSH1) is known to regulate actin filament dynamics by dephosphorylating and activating cofilin, an actin-depolymerizing factor. SSH1 binds to filamentous (F-) actin through its multiple F-actin-binding sites and its cofilin-phosphatase activity is enhanced by binding to F-actin. In this study, we demonstrate that SSH1 has F-actin-stabilizing and -bundling activities. In vitro actin depolymerization assays revealed that SSH1 suppressed spontaneous and cofilin-induced actin depolymerization in a dose-dependent manner. SSH1 inhibited F-actin binding and severing activities of cofilin. Low-speed centrifugation assays combined with fluorescence and electron microscopic analysis revealed that SSH1 has F-actin-bundling activity, independently of its cofilin-phosphatase activity. Deletion of N- or C-terminal regions of SSH1 significantly reduced its F-actin-stabilizing and -bundling activities, indicating that both regions are critical for these functions. As SSH1 does not form a homodimer, it probably bundles F-actin through its multiple F-actin-binding sites. Knockdown of SSH1 expression by RNA interference significantly suppressed stress fiber formation in C2C12 myoblast cells, indicating a role for SSH1 in stress fiber formation or stabilization in cells. SSH1 thus has the potential to regulate actin filament dynamics and organization in cells via F-actin-stabilizing and -bundling activities, in addition to its ability to dephosphorylate cofilin.     

Unenhanced MR Angiography of Uterine and Ovarian Arteries after Uterine Artery Embolization: Differences between Patients with Incomplete and Complete Fibroid Infarction

Purpose

To compare the status of uterine and ovarian arteries after uterine artery embolization (UAE) in patients with incomplete and complete fibroid infarction via unenhanced 3D time-of-flight magnetic resonance (MR) angiography.

Materials and Methods

Thirty-five consecutive women (mean age 43?years; range 26?C52?years) with symptomatic uterine fibroids underwent UAE and MR imaging before and within 2?months after UAE. The patients were divided into incomplete and complete fibroid infarction groups on the basis of the postprocedural gadolinium-enhanced MR imaging findings. Two independent observers reviewed unenhanced MR angiography before and after UAE to determine bilateral uterine and ovarian arterial flow scores. The total arterial flow scores were calculated by summing the scores of the 4 arteries. All scores were compared with the Mann-Whitney test.

Results

Fourteen and 21 patients were assigned to the incomplete and complete fibroid infarction groups, respectively. The total arterial flow score in the incomplete fibroid infarction group was significantly greater than that in the complete fibroid infarction group (P?=?0.019 and P?=?0.038 for observers 1 and 2, respectively). In 3 patients, additional therapy was recommended for insufficient fibroid infarction. In 1 of the 3 patients, bilateral ovarian arteries were invisible before UAE but seemed enlarged after UAE.

Conclusion

The total arterial flow from bilateral uterine and ovarian arteries in patients with incomplete fibroid infarction is less well reduced than in those with complete fibroid infarction. Postprocedural MR angiography provides useful information to estimate the cause of insufficient fibroid infarction in individual cases.     

Thioredoxin in coronary culprit lesions: possible relationship to oxidative stress and intraplaque hemorrhage

The present study investigated the expression of thioredoxin (TRX), an important anti-oxidative protein, and its relationship to plaque instability in atherectomy specimens from 43 and 42 patients with stable (SAP) and unstable (UAP) angina pectoris, respectively. We histologically assessed thrombus formation, cellular elements, localization of TRX and of oxidized low density lipoprotein (ox-LDL), intraplaque hemorrhage, and transition metal iron (Fe(2+), Fe(3+)) deposition in these specimens. The clinical characteristics of the two groups did not differ except for aspirin administration. The incidence of thrombus formation was more frequent (P=0.005) and immunopositive areas of macrophage, TRX and ox-LDL were significantly larger in patients with UAP than SAP (P<0.001, each). Macrophages were mainly immunoreactive for TRX and ox-LDL. Intraplaque hemorrhage evaluated by glycophorin A immunoreactivity and Fe(2+)/Fe(3+) deposition was also more obvious in lesions from patients with UAP than SAP (P<0.001, each). Additionally, immunopositive areas of TRX and ox-LDL positively correlated with Fe(2+)/Fe(3+) deposition and were also associated with thrombus formation. Although the underlying mechanisms remain unknown, TRX was up-regulated in response to increased oxidative stress and associated with intraplaque hemorrhage of coronary culprit lesions, and thus might be a potent marker of plaque instability.     

Inflammatory pseudotumor of the intrapancreatic accessory spleen: computed tomography and magnetic resonance imaging findings

Inflammatory pseudotumor of the spleen is an uncommon benign mass-like lesion. It can occur in an accessory spleen, which may be found rarely in the pancreas tail. Here, we report the case of a 51-year-old woman with an inflammatory pseudotumor of the intrapancreatic accessory spleen mimicking a fibrous pancreatic mass with hemosiderin deposition. To the best of our knowledge, this is the first case report including radiological and histopathological findings of this extremely rare condition. In conclusion, inflammatory pseudotumor of an intrapancreatic accessory spleen should be regarded as a differential diagnosis in the case of a fibrotic mass with hemosiderin deposition located in the pancreas tail.     

Measurement of dyspnea in patients with obstructive sleep apnea

Purpose

Patients with obstructive sleep apnea (OSA) frequently complain of exertional dyspnea. We aimed to assess its related factors and the significance of its measurement in OSA.

Methods

We evaluated 301 subjects with suspected OSA for dyspnea during activities of daily living using the Medical Research Council (MRC) scale. We analyzed the relationships between MRC grades and various subjective and objective indices. Further, the relationship of disease severity based on the apnea/hypopnea index (AHI) with these indices was examined. Results were compared between those obtained using MRC grades and the AHI.

Results

Of 301 subjects, 265 were diagnosed with OSA. Their MRC scores were worse than in non-OSA patients. Among OSA patients, 125 had MRC grade 1 (mild), 121 had MRC grade 2 (moderate), and 19 had MRC grade 3 or more (severe) dyspnea. Various measurements differed significantly between groups categorized according to the MRC scale although determinants between mild and moderate groups and between moderate and severe groups differed. AHI categorizations were not significantly related to patient-reported measurements such as the Medical Outcomes Study 36-item short form, Pittsburgh Sleep Quality Index, and Hospital Anxiety and Depression Scale scores, unlike categorization based on the MRC scale.

Conclusions

Dyspnea is an important outcome in OSA although dyspnea in OSA patients is unrelated to the sleep disorder per se. Measurement of dyspnea in patients with OSA might provide further insights into the health of these patients and clinical manifestations of this disease.