Causes of Death in Patients with Severe Aortic Stenosis: An Observational study.

Whether patients with severe aortic stenosis (AS) die because of AS-related causes is an important issue for the management of these patients. We used data from CURRENT AS registry, a Japanese multicenter registry, to assess the causes of death in severe AS patients and to identify the factors associated with non-cardiac mortality. We enrolled 3815 consecutive patients with a median follow-up of 1176 days; the 1449 overall deaths comprised 802 (55.

Impact of the left ventricular mass index on the outcomes of severe aortic stenosis.

Objective: To elucidate the factors associated with high left ventricular mass index (LVMI) and to test the hypothesis that high LVMI is associated with worse outcome in severe aortic stenosis (AS).

Methods: We analysed 3282 patients with LVMI data in a retrospective multicentre registry enrolling consecutive patients with severe AS in Japan. The management strategy, conservative or initial aortic valve replacement (AVR), was decided by the attending physician.

Three-Dimensional Speckle Tracking Imaging for Assessing Left Atrial Function in Hypertensive Patients With Paroxysmal Atrial Fibrillation.

Hypertension (HT) is known to be the most prevalent risk factor for paroxysmal atrial fibrillation (PAF), however, its mechanisms have not been fully clarified. Our aim was to investigate the differences in left atrial (LA) function between healthy subjects, and hypertensive patients without PAF (HT-PAF(-)) and with PAF (HT-PAF(+)) using 3-dimensional (3D) speckle tracking imaging (STI). A total of 144 subjects were enrolled: 44 HT-PAF(+) (27 males; mean age 69 ± 10 years), 50 HT-PAF(-) (31 males; mean age 63 ± 11 years), and 50 controls (31 males; mean age 51 ± 14 years).

Prospective multi-center registry to evaluate efficacy and safety of the newly developed diamond-like carbon-coated cobalt-chromium coronary stent system.

The purpose of this multi-center, non-randomized, and open-label clinical trial was to determine the non-inferiority of diamond-like carbon (DLC)-coated cobalt-chromium coronary stent, the MOMO DLC coronary stent, relative to commercially available bare-metal stents (MULTI-LINK VISION). Nineteen centers in Japan participated. The study cohort consisted of 99 patients from 19 Japanese centers with single or double native coronary vessel disease with de novo and restenosis lesions who met the study eligibility criteria.

Role of cytosolic phospholipase A(2)α in cell rounding and cytotoxicity induced by ceramide-1-phosphate via ceramide kinase.

Ceramide-1-phosphate (C1P), produced by ceramide kinase (CERK), is implicated in the regulation of many biological functions including cell growth and inflammation. C1P is a direct activator of group IVA cytosolic phospholipsase A(2) (PLA2G4A or cPLA(2)α). Although activation of the CERK-C1P pathway causes mitogenic and cytoprotective responses in many cells, the pathway shows cytotoxicity in several cells and the precise mechanism has not been elucidated.

Activation of ceramidase and ceramide kinase by vanadate via a tyrosine kinase-mediated pathway.

Ceramide, a key molecule in the metabolism of sphingolipids, is converted by ceramidase to sphingosine, and phosphorylated by ceramide kinase to form ceramide-1-phosphate (C1P). In this study, we improved on a method of thin-layer chromatography using a fluorescent ceramide, 4-nitrobenzo-2-oxa-1,3-diazole-labeled C6-ceramide (NBD-ceramide) by adding another step for separation of extracted ceramide metabolites by lipophilicity, and determined levels of C1P, caproic acid, sphingomyelin, and glucosylceramide simultaneously. Also we found that 1) treatment of NBD-ceramide-labeled cells (human lung adenocarcinoma A549 cells and Chinese hamster ovary cells) with Na(3)VO(4) increased the amount of NBD-C1P formed within 30 min, 2) the treatment increased production of NBD-caproic acid, a counterpart of sphingosine, by ceramidase within 2 h, 3) expression of ceramide kinase enhanced the Na(3)VO(4)-induced formation of NBD-C1P, and tyrosine kinase inhibitors (herbimycin and genistein) decreased the response, 4) the production of NBD-caproic acid in A549 cells was inhibited by genistein, and 5) the responses for 2 h after Na(3)VO(4) treatment were accompanied by a decrease in the production of NBD-sphingomyelin, not a loss of NBD-ceramide.

A rare connection by newly formed conduit vessels between the left internal mammalian artery and radial artery bypass grafts after failure of grafts.

Neovascularization such as formation of collateral vessels following total occlusion of native coronary artery is common in coronary artery disease. This is a case report of a very rare connection by newly formed conduit vessels between the left internal mammalian artery and the radial artery establishing bypass, which occurred after failure of bypass grafts.

Dietary polyunsaturated fatty acids slow the progression of diabetic nephropathy in streptozotocin-induced diabetic rats.

Diabetic nephropathy is associated with lipid deposits in the kidney. We hypothesized that a diet containing polyunsaturated fatty acids (PUFAs) could ameliorate pathogenesis of diabetic kidney diseases associated with lipid depositions in the kidneys. We examined if the pathogenesis and progression of diabetic nephropathy are affected by the type of dietary fat using streptozotocin (45 mg/kg body weight, intravenous)-induced diabetic rats (5-week-old male Sprague-Dawley rats).

Effects of synthetic sphingosine-1-phosphate analogs on cytosolic phospholipase A2alpha-independent release of arachidonic acid and cell toxicity in L929 fibrosarcoma cells: the structure-activity relationship.

Sphingolipid metabolites including ceramide, sphingosine, and their phosphorylated products [sphingosine-1-phosphate (S1P) and ceramide-1-phosphate] regulate cell functions including arachidonic acid (AA) metabolism and cell death. The development of analogs of S1P may be useful for regulating these mediator-induced cellular responses. We synthesized new analogs of S1P and examined their effects on the release of AA and cell death in L929 mouse fibrosarcoma cells.

Effects of ceramide, ceramidase inhibition and expression of ceramide kinase on cytosolic phospholipase A2alpha; additional role of ceramide-1-phosphate in phosphorylation and Ca2+ signaling.

Ceramide and the metabolites including ceramide-1-phosphate (C1P) and sphingosine are reported to regulate the release of arachidonic acid (AA) and/or phospholipase A(2) (PLA(2)) activity in many cell types including lymphocytes. Recent studies established that C1P, a product of ceramide kinase, interacts directly with Ca(2+) binding regions in the C2 domain of alpha type cytosolic PLA(2) (cPLA(2)alpha), leading to translocation of the enzyme from the cytosol to the perinuclear region in cells. However, a precise mechanism for C1P-induced activation of cPLA(2)alpha has not been well elucidated; such as the phosphorylation signal caused by the extracellular signal-regulated kinases (ERK1/2) pathway, a downstream of the protein kinase C activation with 4beta-phorbol myristate acetate (PMA), is required or not.

[A case of effective weekly paclitaxel administration for primary lesion of schirrous gastric cancer].

We report a case of advanced schirrous gastric cancer with carcinomatous peritonitis. Chemotherapy with TS-1 was applied during the first 4 weeks, but the tumor did not respond to this therapy. Next, paclitaxel (TXL) was administered at a weekly dose of 90 mg/body/day for 3 weeks followed by a week interval of rest.

X-irradiation causes a prolonged reduction in cell proliferation in the dentate gyrus of adult rats.

The effects of X-irradiation on proliferating cells in the dentate subgranular zone were assessed in young adult Fisher 344 rats exposed to a range of X-ray doses and followed for up to 120 days. Apoptosis was quantified using morphology and end-labeling immunohistochemistry, and cell proliferation was detected using antibodies against the thymidine analog BrdU and the cyclin-dependent kinase p34(cdc2). Radiation-induced apoptosis occurred rapidly, with maximum morphological and end-labeling changes observed 3-6h after irradiation.

Long-term impairment of subependymal repopulation following damage by ionizing irradiation.

In the mammalian brain, the subependyma (SE) contains stem cells capable of producing neurons and glia. In normal brain these stem cells are responsible, in part, for maintaining the morphologic and functional integrity of the SE; what role the cells of the SE play in brain injury has not yet been elucidated. The present study was designed to determine the long-term regenerative potential of the rat SE after significant depletion of stem cells.

Inhibition of dentate granule cell neurogenesis with brain irradiation does not prevent seizure-induced mossy fiber synaptic reorganization in the rat.

Aberrant reorganization of dentate granule cell axons, the mossy fibers, occurs in human temporal lobe epilepsy and rodent epilepsy models. Whether this plasticity results from the remodeling of preexisting mossy fibers or instead reflects an abnormality of developing dentate granule cells is unknown. Because these neurons continue to be generated in the adult rodent and their production increases after seizures, mossy fibers that arise from either developing or mature granule cells are potential substrates for this network plasticity.

Combined brachytherapy and external beam radiotherapy in normal monkey brains--experimental radiation necrosis evaluated by sequential magnetic resonance imaging.

Radiation-induced brain damage was evaluated using sequential magnetic resonance (MR) imaging in monkeys more than 1 year after either brachytherapy or combined brachytherapy and external beam radiotherapy (EBRT). MR images were obtained 1 week, 1 month, 3 months, and subsequently every 3 months after brachytherapy, and the volume of the lesions was measured. In all four monkeys receiving only brachytherapy and three of the four animals receiving combined brachytherapy and EBRT, MR imaging revealed only transient extensive edema 1 week after treatment and ring enhancement, which was maximal 3 months after treatment, surrounding the implantation site.

Effect of adjuvant iridium-192 brachytherapy on the survival of patients with malignant gliomas.

The effect of iridium-192 brachytherapy (BRTX) on the survival of patients with malignant gliomas was evaluated in 83 patients with malignant gliomas (42 astrocytoma grade III, 41 glioblastoma multiforme) over a period of 8.5 years. Fifty patients (Group 1) received only standard external beam radiotherapy (EBRT) (mean dose 51.

Stereotactic brachytherapy for a cystic metastatic brain tumor in the midbrain. Case report.

The authors report a rare case of a cystic metastasis in the midbrain that was successfully treated by brachytherapy following stereotactic biopsy and aspiration of the intratumoral cyst. Stereotactic aspiration of cystic lesions can lead to clinical improvement and brachytherapy prevents cyst recurrence. A 46-year-old man was referred to the authors' institution with a 2-month history of a left hemisensory disturbance and a 1-month history of progressive hemiparesis.

Proton MR spectroscopy of delayed cerebral radiation in monkeys and humans after brachytherapy.

Purpose: To determine whether radiation necrosis can be differentiated from residual/recurrent tumor by proton MR spectroscopy.

Methods: We studied the effects of interstitial brachytherapy on the brains of healthy monkeys and in humans with glioblastoma multiforme. The effects of radiation therapy on normal brain tissue in monkeys were assessed with sequential proton MR spectroscopic studies 1 week to 6 months after brachytherapy.

The protective effect of dexamethasone against radiation damage induced by interstitial irradiation in normal monkey brain.

Objective: The protective effect of dexamethasone against radiation damage is unclear. We examined the effect of early treatment of high-dose dexamethasone on iridium-192-induced damage to normal brain tissue.

Methods: Brain damage induced by interstitial irradiation with iridium-192 was evaluated with sequential magnetic resonance imaging and proton magnetic resonance spectroscopy in 11 adult monkeys, with or without short-term high-dose dexamethasone treatment.

Apoptosis in the subependyma of young adult rats after single and fractionated doses of X-rays.

Ionizing radiation is commonly used in the treatment of brain tumors but can cause significant damage to surrounding normal brain. The pathogenesis of this damage is uncertain, and understanding the response of potential target cell populations may provide information useful for developing strategies to optimize therapeutic irradiation. In the mammalian forebrain, the subependyma is a mitotically active area that is a source of oligodendrocytes and astrocytes, and it has been hypothesized that depletion of cells from this region could play a role in radiation-induced white matter injury.

[Usefulness of neoadjuvant brachytherapy in the treatment of pineoblastoma: a case report].

The treatment strategy and prognosis of pineal cell tumors are still subjects of debate because of their rarity and the mixture of pineoblastoma and pineocytoma as components. Pineoblastoma is believed to be the more malignant tumor and total gross resection of this tumor is very difficult because of its invasive tendency and location. Although the effectiveness of external irradiation and chemotherapy has been reported, the outlook for patients with this tumor is extremely poor.