Cdc48 and its co-factor Ufd1 extract CENP-A from centromeric chromatin and can induce chromosome elimination in the fission yeast Schizosaccharomyces pombe.

CENP-A determines the identity of the centromere. Because the position and size of the centromere and its number per chromosome must be maintained, the distribution of CENP-A is strictly regulated. In this study, we have aimed to understand mechanisms to regulate the distribution of CENP-A (Cnp1SP) in fission yeast. A mutant of the ufd1+ gene (ufd1-73) encoding a cofactor of Cdc48 ATPase is sensitive to Cnp1 expressed at a high level and allows mislocalization of Cnp1. The level of Cnp1 in centromeric chromatin is increased in the ufd1-73 mutant even when Cnp1 is expressed at a normal level. A preexisting mutant of the cdc48+ gene (cdc48-353) phenocopies the ufd1-73 mutant. We have also shown that Cdc48 and Ufd1 proteins interact physically with centromeric chromatin. Finally, Cdc48 ATPase with Ufd1 artificially recruited to the centromere of a mini-chromosome (Ch16) induce a loss of Cnp1 from Ch16, leading to an increased rate of chromosome loss. It appears that Cdc48 ATPase, together with its cofactor Ufd1 remove excess Cnp1 from chromatin, likely in a direct manner. This mechanism may play a role in centromere disassembly, a process to eliminate Cnp1 to inactivate the kinetochore function during development, differentiation, and stress response.

Mild hyperbaric oxygen exposure attenuates rarefaction of capillary vessels in streptozotocin-induced diabetic soleus muscle in rats.

We examined the effects of mild hyperbaric oxygen (mHBO) exposure on capillary rarefaction in skeletal muscles of rats with diabetes. Streptozotocin (100 mg/kg) was administered to male Wistar rats via the tail vein to prepare a diabetic model. These rats were divided into 2 groups: the group with mHBO exposure (1.25 atmospheres absolute (ATA) with 36% oxygen; 3 h/day) and the group without mHBO exposure. Age-matched rats were used as the control group. Eight weeks later, the soleus of the rats was removed and then analyzed. With the onset of diabetes mellitus, capillary number, diameter, and volume in the soleus of the rats with diabetes decreased compared with those of the rats in the control group. In addition, increased anti-angiogenic thrombospondin-1 (TSP-1) and decreased pro-angiogenic murine double minute 2 (MDM-2) protein expressions were observed in the rats with diabetes. Alternatively, mHBO exposure attenuated the decrease in capillary diameter and volume in skeletal muscles of rats with diabetes, suppressed the overexpression of TSP-1, and restored the MDM-2 expression. These results indicate the exposure of mHBO partially attenuates capillary rarefaction in diabetic soleus muscle.

Preventive effects of medium-chain triglycerides supplementation on the oxidative capacity in skeletal muscle under cachectic condition.

Cachexia is a multifactorial condition characterized by muscle mass loss and induces metabolic dysfunction of the skeletal muscles. The preventive effects of medium-chain triglycerides (MCT) supplementation on the oxidative capacity in skeletal muscle under cachectic condition were investigated in the present study. ICR mice were randomly divided into four groups; control, lipopolysaccharide (LPS), LPS plus long-chain triglycerides (LCT) and LPS plus MCT supplementation. LCT and MCT oil were administered to the LPS + LCT and LPS + MCT groups orally (5.0 g/kg body weight/day) by a catheter for one week. Cachexia was induced in the LPS, LPS + LCT, and LPS + MCT groups via LPS injection (7.5 mg/kg body weight, i.p.) after the supplementation. LPS induced a reduction of ketone bodies concentration in blood plasma. LPS also induced a decrease in succinate dehydrogenase activity and PGC-1α expression level in tibialis anterior muscles. Meanwhile, MCT supplementation suppressed a decrease in ketone bodies concentration and succinate dehydrogenase activity. In addition, MCT supplementation increased the level of citrate synthase activity in the muscles. These results suggested the preventive effect of MCT supplementation on oxidative capacity in skeletal muscle and the involvements of ketone bodies regulation under cachectic condition.

Effects of combined treatment with blood flow restriction and low-current electrical stimulation on muscle hypertrophy in rats.

This study aimed to clarify the effects of a combined treatment comprising blood flow restriction and low-current electrical stimulation on skeletal muscle hypertrophy in rats. Male Wistar rats were divided into control (Cont), blood flow restriction (Bfr), electrical stimulation (Es), or Bfr with Es (Bfr + Es) groups. Pressure cuffs (80 mmHg) were placed around the thighs of Bfr and Bfr + Es rats. Low-current Es was applied to calf muscles in the Es and Bfr + Es rats. In experiment 1, a 1-day treatment regimen (5-min stimulation, followed by 5-min rest) was delivered four times to study the acute effects. In experiment 2, the same treatment regimen was delivered three times/wk for 8 wk. Body weight, muscle mass, changes in maximal isometric contraction, fiber cross-sectional area of the soleus muscle, expression of phosphorylated and total-ERK1/2, phosphorylated-rpS6 Ser235/236, phosphorylated and total Akt, and phosphorylated-rpS6 Ser240/244 were measured. Bfr and Es treatment alone failed to induce muscle hypertrophy and increase the expression of phosphorylated rpS6 Ser240/244. Combined Bfr + Es upregulated muscle mass, increased the fiber cross-sectional area, and increased phosphorylated rpS6 Ser240/244 expression and phosphorylated rpS6 Ser235/236 expression compared with controls. Combined treatment with Bfr and low-current Es can induce muscle hypertrophy via activation of two protein synthesis signaling pathways. This treatment should be introduced for older patients with sarcopenia and others with muscle weakness.NEW & NOTEWORTHY We investigated the acute and chronic effect of low-current electrical stimulation with blood flow restriction on skeletal muscle hypertrophy and the mechanisms controlling the hypertrophic response. Low-current electrical stimulation could not induce skeletal muscle hypertrophy, but a combination treatment did. Blood lactate and growth hormone levels were increased in the early response. Moreover, activation of ERK1/2 and mTOR pathways were observed in both the acute and chronic response, which contribute to muscle hypertrophy.

Lymphangiography and Post-lymphangiographic Multidetector CT for Preclinical Lymphatic Interventions in a Rabbit Model.

PURPOSE: To describe the feasibility of lymphangiography and the visibility of the lymphatic system using post-lymphangiographic multidetector CT (MDCT) for preclinical lymphatic interventions in a rabbit model. MATERIALS AND METHODS: Lymphangiography via the popliteal lymph node or vessel after surgical exposure was performed, using six healthy female Japanese White rabbits. Lipiodol was manually injected for lymphangiography. Post-lymphangiographic MDCT examinations were performed in all rabbits. The dataset images were subjected to image processing analysis utilizing the three-dimensional maximum intensity projection technique. Three reviewers evaluated the degree of depiction of the lymphatic system using a four-point visual score (1, poor; 2, fair; 3, good; 4, excellent). The distance between the body surface and cisterna chyli was measured on post-lymphangiographic MDCT axial image. RESULTS: Lymphangiography was successfully performed in all rabbits. The popliteal lymph node was detectable in 90%. The visualization of lymphatic system via the popliteal node was achieved in 89%. Mean visual scores of > 3.0 were realized by the right femoral lymphatic vessel, left femoral lymphatic vessel, left iliac lymphatic vessel, left lumbar lymphatic trunks and cisterna chyli, whereas mean visual scores of < 3.0 were yielded by the right iliac lymphatic vessel, right lumbar lymphatic trunks and thoracic duct. The distance between the body surface and cisterna chyli on post-lymphangiographic MDCT axial images was 4.33 ± 0.14 cm. CONCLUSION: Lymphangiography is feasible, and the visibility of the lymphatic system on post-lymphangiographic MDCT in a rabbit model provides enough information for interventional radiologists to perform preclinical lymphatic interventions.

Feasibility and Safety of Repeated Transarterial Chemoembolization Using Miriplatin-Lipiodol Suspension for Hepatocellular Carcinoma.

AIM: To retrospectively evaluate the feasibility and safety of repeated transarterial chemoembolization (TACE) three or more times using miriplatin-lipiodol (M-LPD) suspension (repeated M-LPD TACE) for hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Sixteen patients who underwent repeated M-LPD TACE were examined. Total dose of miriplatin, lipiodol and porous gelatin sponge particles and adverse events of the first and last M-LPD TACE were evaluated. RESULTS: The mean±standard deviation (SD) of the total number of M-LPD TACE per patient was 3.7±1.1. The mean±SD dose of total miriplatin, lipiodol and porous gelatin sponge particles per patient was 303±103 mg, 21±7.3 ml and 84±57 mg, respectively. There were no significant differences in any adverse events between the first and last M-LPD TACE. CONCLUSION: Repeated M-LPD TACE for HCC is feasible and safe in selected patients.

Balloon-occluded transarterial chemoembolization using a 1.8-French tip coaxial microballoon catheter for hepatocellular carcinoma: technical and safety considerations.

OBJECTIVE: To evaluate the technical feasibility and safety considerations of balloon-occluded transarterial chemoembolization (B-TACE) using a newly developed 1.8-French (Fr) tip microballoon catheter for hepatocellular carcinoma (HCC). MATERIAL AND METHODS: Between February 2013 and May 2013, 31 patients (20 males, 11 females; age range 56-85 years) underwent B-TACE using a 1.8-Fr tip microballoon catheter for unresectable HCC. The technical success rate, procedural complications, and adverse events of B-TACE were retrospectively investigated. RESULTS: A total of 31 patients were subjected to 70 sessions of B-TACE using a 1.8-Fr tip microballoon catheter. The level of B-TACE was sub-subsegmental in 11, subsegmental in 35, segmental in 14, lobar in five, and right inferior phrenic artery in five sessions. The overall technical success rate was 99% (69 out of 70 sessions). As procedural complications, rupturing of the microballoon (n = 3) and aneurysmal dilatation at the site of balloon occlusion (n = 2) were encountered. There were no significant differences in any parameters between blood biochemical examination before and between two to four weeks after the procedure. CONCLUSION: A 1.8-Fr tip microballoon catheter enables selective catheterization in patients with HCC and B-TACE using the 1.8-Fr tip microballoon catheter is a safe procedure.

Prediction of therapeutic effectiveness according to CT findings after therapeutic lymphangiography for lymphatic leakage.

PURPOSE: To evaluate the correlation between computed tomography (CT) findings after therapeutic lymphangiography for lymphatic leakage and the clinical course of lymphatic leakage. MATERIALS AND METHODS: Therapeutic lymphangiography for lymphatic leakage was performed in 14 patients. In all patients, CT was performed 0.5-26 h (mean 6.9 h) after lymphangiography and results were retrospectively evaluated. RESULTS: In 8 of the 14 patients (57 %), lymphatic leakage stopped after lymphangiography. Lymphatic leakage was detected on CT in 9 of the 14 patients (64 %) and had either a nodular (n = 4) or beaded appearance (n = 5). The amount of drainage had decreased the day after lymphangiography, and leakage finally stopped in all 4 patients in whom the leakage had a nodular appearance. However, leakage did not stop in 3 of the 5 patients having leakage with a beaded appearance. CONCLUSION: A nodular appearance of leakage might predict success of therapeutic lymphangiography.

Transcatheter arterial embolization with N-butyl cyanoacrylate for acute life-threatening gastroduodenal bleeding uncontrolled by endoscopic hemostasis.

PURPOSE: To investigate the feasibility, efficacy, and safety of transcatheter arterial embolization with N-butyl cyanoacrylate (NBCA) for gastroduodenal nonvariceal bleeding uncontrolled by endoscopic hemostasis. MATERIALS AND METHODS: Between January 2006 and December 2011, a total of 317 patients underwent emergent endoscopic therapy for nonvariceal gastroduodenal bleeding, but hemostasis was not achieved in 20 cases. Emergent surgery was performed immediately following endoscopy in two patients. Arteriography was performed in the remaining 18 patients, and embolization with NBCA was performed in 15 patients (mean age, 71.3 y) in whom the bleeding site was detected on arteriography. For embolization, NBCA was mixed with iodized oil at a ratio of 1:1.5-1:4, and no other embolic material was used in the procedure. Technical and clinical success rates, recurrent bleeding, procedural time, complications, and clinical outcomes were determined for each procedure. RESULTS: Embolization with NBCA was technically and clinically successful in all procedures, without major complications. No patient receiving embolization with NBCA experienced recurrent bleeding or required further treatment after the one-session procedure. All patients were discharged after clinical improvement. The time between puncture of the femoral artery and completion of embolization ranged from 25 to 240 minutes (mean, 66 min), and the time between the microcatheter reaching the ultimate catheter location selected for embolization and hemostasis ranged from 142 to 550 seconds (mean, 322s). CONCLUSIONS: In this limited series, embolization with NBCA was found to be a safe, feasible, and effective treatment for gastroduodenal arterial bleeding when endoscopic hemostasis had failed.

A new flow control technique using diluted epinephrine in the N-butyl-2-cyanoacrylate embolization of visceral artery pseudoaneurysms secondary to chronic pancreatitis.

Although n-butyl-2-cyanoacrylate (NBCA) has been used as an effective liquid embolization material, its indication for pseudoaneurysms has seemingly been limited because of the technical difficulties of using NBCA, such as reflux to the parent artery and causing significant infarction. Thus, considerable skill in using NBCA or a device to control blood flow during its polymerization is required to achieve embolization without severe complications. We report our new technique for controlling blood flow using diluted epinephrine in transcatheter arterial NBCA embolization of five pseudoaneurysms in four cases secondary to hemosuccus pancreaticus.

Osteogenic potential of rat stromal cells derived from periodontal ligament.

Various mesenchymal stromal cells (MSCs) have been applied to regenerative medicine. MSCs derived from periodontal tissue could also be a useful cell source for alveolar bone regeneration. However, only a few attempts of direct comparisons have been made between MSCs from periodontal tissues and those from other somatic tissues. The purpose of this study was to clarify the osteogenic characteristics of mesenchymal stromal cells derived from bone marrow (BMSCs), adipose tissue (ASCs) and periodontal ligament (PDLSCs). BMSCs, ASCs and PDLSCs were isolated from Fisher 344 rats. After 1 week of primary culture, stromal cells were subjected to cell surface analysis and osteogenic differentiation. The cells were subcultured for 2 weeks with and without osteogenic supplements (OS), followed by biochemical and histological analyses. With regard to cell surface antigens, all MSCs were positive for CD29 and CD90 and negative for CD45. With regard to osteogenic differentiation, BMSCs with OS had the highest ALP activity, calcium uptake and osteocalcin content. Without OS, PDLSCs had the highest levels of these bone differentiation markers. RT-PCR analysis and histological analysis showed similar trends. These results indicate that PDLSCs are an ideal candidate for alveolar bone regeneration.

Endovascular repair of a perforation of the vena caval wall caused by the retrieval of a Gunther Tulip filter after long-term implantation.

Symptomatic penetration of the inferior vena cava (IVC) wall reportedly occurs in 0.3% of patients in whom a filter has been implanted, and it causes injury to the adjacent structures (Bogue et al. in Pediatr Radiol 39(10):1110-1113, 1; Brzezinski et al. in Burns 32(5):640-643, 2). We succeeded in the endovascular repair of perforation of the IVC wall occurring during the retrieval of a penetrated Gunther tulip vena cava filter (Cook, Bjaeverskov, Denmark) after long-term implantation.