Biomedical subjects

Susumu Ishikawa

Publications and source records attributed to Susumu Ishikawa.

At least 19 recordsLinked to original sources

PubMed2007

Progression of abdominal aortic aneurysm after endovascular stent-grafting in a patient with Behçet's disease: report of a case.

A 53-year-old man with Behçet's disease was admitted to our hospital for investigation of back and lower abdominal pain. Computed tomography (CT) showed a projecting saccular aneurysm below the right renal artery. We placed a stent-graft just below the right renal artery, successfully excluding the abdominal aortic aneurysm (AAA). His C-reactive protein level and white blood cell count remained elevated after stent-grafting. About 5 months later, he was readmitted with recurrent back and lower abdominal pain and CT showed progression of the AAA. Thus, we performed straight grafting using a woven Dacron graft just below the right renal artery. The patient had an uneventful postoperative course. We discuss the controversial issue of treating AAA in patients with Behçet's disease, focusing on the indications and timing of surgery.

Aortic Aneurysm, Abdominal↗

PubMed2006

Beraprost sodium-induced hypotension in two patients after cardiac surgery.

Two episodes of hypotension caused by oral beraprost sodium administration following cardiac surgery are described. The first case was a 67-year-old female who underwent concomitant surgery for mitral valve replacement, tricuspid annuloplasty, and a radiofrequency maze procedure for atrial fibrillation. The second case was a 45-year-old female who underwent 4-vessel coronary artery bypass grafting associated with endarterectomy in the right coronary artery. Beraprost sodium was administered for the treatment of residual pulmonary hypertension in the first case, and was initiated as an antiplatelet agent following coronary endarterectomy in the second case. Hypotension occurred at approximately one hour after beraprost sodium administration in both cases. Careful observation to prevent this adverse effect is critical after the administration of beraprost sodium, especially in patients who have undergone cardiac surgery.

Aged↗

PubMed2005

Downregulation of cyclin-dependent kinase inhibitor; p57(kip2), is involved in the cell cycle progression of vascular smooth muscle cells.

Immature vascular smooth muscle cells (VSMCs) proliferate responding to extrinsic mitogens and accumulate in neointima after arterial injuries. Cell proliferation is positively regulated by cyclin/cyclin-dependent kinase (CDK) complex and negatively controlled by CDK inhibitors; CKIs such as p27(kip1) and p57(kip2). In this study, embryonic rat thoracic aorta VSMCs; A10 were G0/G1 arrested by serum starvation, re-stimulated with serum, and harvested every four hours. Both CKIs co-expressed in quiescent VSMCs and rapidly diminished by stimulation. Protein level of p27(kip1) was regulated by both transcription and post-transcription, but that of p57(kip2) was mainly by post-transcription. Supplemental overexpression of p57(kip2) inhibited the activations of G1 cyclin/CDKs and subsequent hyperphosphorylations of all three retinoblastoma pocket proteins as well as G1/S transition of cell cycle. Our findings suggest that the downregulations of not only p27(kip1), but also p57(kip2) responding to mitogenic stimulation, play key roles in the cell cycle progression of VSMCs.

Animals↗

PubMed2005

Paired-like homeoprotein ESXR1 acts as a sequence-specific transcriptional repressor of the human K-ras gene.

Gain-of-function mutation of the K-ras gene is one of the most common genetic changes in human tumors. In tumors carrying K-ras mutation, the presence of oncogenic K-Ras is necessary for maintenance of the transformed phenotype. ESXR1 is a human paired-like homeodomain-containing protein expressed primarily in the testis. In cells, the 65-kDa full-length ESXR1 protein is proteolytically processed into an N-terminal 45-kDa fragment containing the homeodomain, which localizes exclusively within the nucleus, and a C-terminal 20-kDa fragment consisting of a proline-rich repeat region, which is located in the cytoplasm. In this work, we demonstrated that the N-terminal ESXR1 fragment specifically recognizes the TAATNNNATTA P3 consensus sequence for the paired-like homeodomain and functions as a sequence-specific transcriptional repressor. We also showed that the N-terminal ESXR1 fragment binds to the TAATGTTATTA sequence present within the first intron of the human K-ras gene and inhibits its expression at both mRNA and protein levels. Ectopic expression of the N-terminal ESXR1 fragment in human carcinoma cells that carry mutated K-ras reduces the level of K-Ras and thereby inhibits the tumor cell proliferation. Identification of ESXR1 as a transcriptional repressor of K-ras has an important implication for the development of cancer therapy that inhibits oncogenic K-Ras expression.

Animals↗

PubMed2005

Functional antagonism between Helicobacter pylori CagA and vacuolating toxin VacA in control of the NFAT signaling pathway in gastric epithelial cells.

Chronic infection with cagA-positive Helicobacter pylori is associated with the development of atrophic gastritis, peptic ulcers, and gastric adenocarcinoma. The cagA gene product CagA is injected into gastric epithelial cells, where it undergoes tyrosine phosphorylation by Src family kinases. Translocated CagA disturbs cellular functions by physically interacting with and deregulating intracellular signaling transducers through both tyrosine phosphorylation-dependent and -independent mechanisms. To gain further insights into the pathophysiological activities of CagA in gastric epithelial cells, we executed a genome-wide screening of CagA-responsive genes by using DNA microarray and identified nuclear factor of activated T cells (NFAT) transcription factors whose binding sites were overrepresented in the promoter regions of CagA-activated genes. Results of reporter assays confirmed that CagA was capable of activating NFAT in a manner independent of CagA phosphorylation. Expression of CagA in gastric epithelial cells provoked translocation of NFATc3, a member of the NFAT family, from the cytoplasm to the nucleus and activated an NFAT-regulated gene, p21WAF1/Cip1. CagA-mediated NFAT activation was abolished by inhibiting calcineurin or phospholipase Cgamma activity. Furthermore, treatment of cells with H. pylori VacA (vacuolating toxin), which inhibits NFAT activity in T lymphocytes, counteracted the ability of CagA to activate NFAT in gastric epithelial cells. These findings indicate that the two major H. pylori virulence factors inversely control NFAT activity. Considering the pleiotropic roles of NFAT in cell growth and differentiation, deregulation of NFAT, either positively or negatively, depending on the relative exposure of cells to CagA and VacA, may contribute to the various disease outcomes caused by H. pylori infection.

Antigens, Bacterial↗

PubMed2005

Long-term preservation using a new apparatus combined with suppression of pro-inflammatory cytokines improves donor heart function after transplantation in a canine model.

OBJECTIVE: We developed a new apparatus for long-term heart preservation that combines simple immersion with coronary perfusion. In a previous study, we reported that suppression of pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF-alpha) and interleukin-1beta (IL-1beta), improved results after transplantation. In this study, we evaluated whether long-term preservation using our apparatus for continuous coronary perfusion, combined with suppression of pro-inflammatory cytokines, improves donor heart function after transplantation in a canine model. METHODS: We used adult mongrel dogs in this study. Coronary vascular beds were washed with University of Wisconsin (UW) solution after arresting hearts with glucose-insulin-potassium solution. The heart was then excised and preserved for 12 hours with a combination of immersion and coronary perfusion using a preservation apparatus. Adult mongrel dogs were divided into 2 groups: the coronary perfusion (CP) group (n = 7) and the FR167653 (FR-CP) group (n = 6). In the CP group, we used a 4 degrees C UW solution for immersion and coronary perfusion. In the FR-CP group, we used a 4 degrees C UW solution supplemented with 20 mg/liter of the anti-inflammatory agent FR167653 for immersion and coronary perfusion. At 2 and at 3 hours after orthotopic transplantation, we compared hemodynamic parameters with pre-operative values in donor animals, with right atrial pressure at 10 mm Hg and with 5 microg/kg/min dopamine infusion. We compared serum concentrations of TNF-alpha from the coronary sinus and compared electron microscopic studies between the 2 groups. RESULTS: Three hours after transplantation, cardiac output (CO), left ventricular pressure (LVP), and -LVdp/dt were significantly greater (p < 0.05) in the FR-CP group than in the CP group (CO, 178% +/- 65% vs 93% +/- 40%; LVP, 115% +/- 22% vs 73% +/-26%; -LVdp/dt, 168% +/- 13% vs 61% +/- 17%, respectively). Electron microscopic studies showed that glycogen was well preserved in the FR-CP group compared with the CP group. Serum concentrations of TNF-alpha were decreased significantly in the FR-CP group compared with the CP group at 3 hours after reperfusion (161 +/- 54 pg/dl vs 642 +/- 636 pg/dl, respectively). CONCLUSION: Hemodynamics after transplantation were significantly better in the FR-CP group than in the CP group. The combined preservation method of continuous perfusion and immersion using our apparatus in conjunction with suppression of pro-inflammatory cytokines improves donor heart function after transplantation.

Animals↗

PubMed2005

Support adapter for radiofrequency ablation probe: experimental study.

BACKGROUND: The purpose of the present study was to experimentally evaluate a new support adapter, which was created in order to insure a more complete contact between the ablation probe and a beating heart. METHODS: Support sleeve adapters for the Cobra Cooled probe were fashioned using a semi-rigid plastic. Forty epicardial radiofrequency ablation (RFA) lesions were created on both atria under the condition of a beating heart in six pigs weighing 26-30 kg. A Cobra Cooled surgical probe was used with continuous internal irrigation of a saline solution (500 mL/h). The ablation temperature was fixed at 80 degrees C and the duration of the RFA in each case was 20, 30 and 60 s. RESULTS: A support adapter ensured a more complete epicardial contact between the probe and a beating heart. An RFA probe supported by the adapter delivered greater power to the tissue. The histopathological transmural coagulation was obtained in 82% and 72% in RFA lesions with and without the adaptor, respectively. CONCLUSION: A new adapter was effective in the epicardial RFA under the condition of a beating heart.

Animals↗

PubMed2005

Mitral regurgitation with an isolated anterior mitral leaflet cleft: a case report.

A 20-year-old man was admitted to hospital because of general fatigue during exercise. He had had a heart murmur since the age of 6 years. Echocardiography showed severe mitral regurgitation (MR, IV), probably caused by an anterior leaflet cleft or tendon rupture. During surgery, a cleft measuring 9 mm in length was found in the center of the anterior leaflet of the mitral valve. The cleft was closed directly, together with annuloplasty using the bilateral Kay's method. A Cosgrove ring (32 mm) was added because the mitral valve annulus was dilated. The patient's postoperative course was uneventful and echocardiography after surgery demonstrated no MR. An isolated cleft of the anterior mitral leaflet is a rare cause of MR and in this case, direct closure of the cleft with additional annuloplasty gave a good functional result.

Adult↗

PubMed2005

Epicardial radiofrequency ablation on a beating heart: an experimental study.

PURPOSE: The effect of epicardial radiofrequency ablation (RFA) during normal heart beating was experimentally studied in order to establish safe and effective procedures for RFA. METHODS: Seven pigs weighing approximately 30 to 50 kg were used in this study. Fifty-one epicardial RFA lesions were created on both atria using a Cobra Cooled probe with continuous internal irrigation of a saline solution. The ablation temperature was fixed at 80 degrees C and the duration of the RFA in each case was 20, 30, 60 and 120 seconds. RESULTS: There was significant positive correlation between the right and left atria in wall thickness. Transmural coagulation was obtained in 69% of the total specimens, which decreased according to the increase of wall thickness especially over 3 mm. Transmural coagulation was seen in 64% of the specimens after RFA of less than 30 seconds, and 86% after ablation of >or=60 seconds. Occurence of 90% or deeper coagulation was higher in the right atrium than in the left one (97% vs. 78%). Right atrial rupture occurred in a region of 1 mm in thickness after ablation of 60 seconds. CONCLUSION: Further technical improvements associated with new instruments are indispensable to complete epicardial RFA procedures on a beating heart.

Animals↗

PubMed2005

[Cardiac rupture caused by myocardial infarction in the diagonal branch area: evaluation by cardiac multislice computed tomography: a case report].

A 75-year-old woman was admitted to the emergency room because of hypotension and loss of consciousness induced by cardiac tamponade. Electrocardiography revealed ST elevation and laboratory data showed elevation of serum creatine kinase and troponin I. The patient was referred to the cardiology department 5 days later. Cardiac catheterization revealed ventricular aneurysm in the anterior wall, significant stenosis (75%) in the left anterior descending coronary artery and subtotal stenosis (99%) in the diagonal branch. Cardiac multislice computed tomography suggested that the ventricular pseudoaneurysm was probably due to cardiac rupture caused by myocardial infarction in the diagonal area. Subsequently, aneurysmectomy and coronary artery bypass graft surgery were performed. Cardiac multislice computed tomography is useful for evaluating coronary artery and cardiac rupture.

Aged↗

PubMed2004

Expression of AIE-75 PDZ-domain protein induces G2/M cell cycle arrest in human colorectal adenocarcinoma SW480 cells.

AIE-75 has been known as a 75-kDa autoantigen detected in the serum of autoimmune enteropathy (AIE) and as a colon cancer-related antigen, and now designated as a gene causative of Usher syndrome type 1C hereditary syndromic hearing loss. It binds to a novel putative tumor suppressor MCC2 that is homologous to MCC (mutated in colon cancer) through a PSD-95/Dlg/ZO-1 (PDZ) domain. To clarify the functional role in colon cancer cells, we transfected AIE-75 gene into SW480 colon cancer cells which do not express AIE-75. Expression of AIE-75 suppressed growth of SW480 cells in vitro in correlation with the expression levels. It was due mainly to G2/M phase cell cycle arrest associated with mitotic slippage, resulting in emergence of hyperploid giant-nucleated or multi-nucleated cells. Screening of proteins that bound to PDZ domains of AIE-75 by a yeast two hybrid system showed that three serine/threonine phosphatase catalytic subunits (PP2AC-alpha, PP2AC-beta, and PPP6C) could bind to AIE-75. Since PP2AC is known to regulate G2/M checkpoint, we suggest that AIE-75 interacts with PP2AC and prevent cells to transit mitotic phase.

Adaptor Proteins, Signal Transducing↗

PubMed2004

Helicobacter pylori CagA induces Ras-independent morphogenetic response through SHP-2 recruitment and activation.

The CagA protein of Helicobacter pylori, which is injected from the bacteria into bacteria-attached gastric epithelial cells, is associated with gastric carcinoma. CagA is tyrosine-phosphorylated by Src family kinases, binds the SH2 domain-containing SHP-2 phosphatase in a tyrosine phosphorylation-dependent manner, and deregulates its enzymatic activity. We established AGS human gastric epithelial cells that inducibly express wild-type or a phosphorylation-resistant CagA, in which tyrosine residues constituting the EPIYA motifs were substituted with alanines. Upon induction, wild-type CagA, but not the mutant CagA, elicited strong elongation of cell shape, termed the "hummingbird" phenotype. Time-lapse video microscopic analysis revealed that the CagA-expressing cells exhibited a marked increase in cell motility with successive rounds of elongation-contraction processes. Inhibition of CagA phosphorylation by an Src kinase inhibitor, PP2, or knockdown of SHP-2 expression by small interference RNA (siRNA) abolished the CagA-mediated hummingbird phenotype. The morphogenetic activity of CagA also required Erk MAPK but was independent of Ras or Grb2. In AGS cells, CagA prolonged duration of Erk activation in response to serum stimulation. Conversely, inhibition of SHP-2 expression by siRNA abolished the sustained Erk activation. Thus, SHP-2 acts as a positive regulator of Erk activity in AGS cells. These results indicate that SHP-2 is involved in the Ras-independent modification of Erk signals that is necessary for the morphogenetic activity of CagA. Our work therefore suggests a key role of SHP-2 in the pathological activity of H. pylori virulence factor CagA.

Animals↗

PubMed2004

Screening cost for abdominal aortic aneurysms: Japan-based estimates.

PURPOSE: The aim of this study was to evaluate the screening procedures in Japan economically focusing on the screening costs and the hospital costs for abdominal aortic aneurysm (AAA) surgery. METHODS: A total of 10,057 residents, 60 years of age or older, including 4 247 men and 5 810 women, participated in the screening test for AAA using ultrasound. RESULTS: Aneurysms were detected in 34 participants, including 32 men and 2 women. The detection rate of AAA was 0.8% in men, 0.03% in women, and 0.3% in total. It cost 8 US dollars to screen each participant, and the cost to detect each aneurysm was thus estimated at 1,250 dollars in men, 23,240 dollars in women, and 2,366 dollars in total. The difference in the mean hospital cost between ruptured and nonruptured AAA was 21,833 dollars in our recent cases. Obesity, male sex, and smoking habits were all significant risk factors for AAA. CONCLUSION: Screening for AAA using ultrasound is useful not only for the early detection of AAA but also for a reduction in the overall medical cost.

Aged↗

PubMed2004

Bombyx Y-box protein BYB facilitates specific DNA interaction of various DNA binding proteins independently of the cold shock domain.

A new member of the Y-box protein family of the silkworm Bombyx mori (BYB) was co-purified with the fibroin gene enhancer-binding protein FMBP-1, and stimulated the binding of FMBP-1 to its cognate DNA element. However, the stimulatory effect was not specific to FMBP-1, BYB also enhancing the binding of mammalian transcription factors OTF2, SP1 and AP2 to their specific binding elements. Besides the above transcription regulatory factors, BYB facilitated the binding of basal transcription factor TBP, and enhanced transcription from the adenovirus 2 major late promoter in a reconstituted transcription system. Moreover, BYB stimulated the reactions of some restriction endonucleases under cold conditions. The C-terminal region of BYB was sufficient for these stimulatory effects, and the highly conserved cold shock domain (CSD) in the N-terminal region was dispensable. GST-pull down experiments showed that the C-terminal region could interact with DNA independently of the CSD. The above results suggest that the C-terminal region of BYB causes the active interaction of various DNA binding proteins with their targets. Such a function of the C-terminal region of BYB may partly explain the functional diversity of Y-box proteins.

Amino Acid Sequence↗

PubMed2004

Cardiac surgery in octogenarians.

BACKGROUND: Early and late results were studied in order to improve the indications for surgery in the elderly. METHODS: Two hundred and thirty-seven patients aged 80 years or older underwent cardiac surgery between 1987 and 2001. The mean age of patients, which included 148 men and 89 women, was 82 years. Elective operations were performed in 194 patients and urgent or emergency operations in 43. Coronary artery bypass grafting (CABG) was performed in 104 patients, valve surgery in 60, CABG plus valve in 58, and other surgery in 15. Late results were obtained in 91% of patients, and the mean follow-up period was 54 months. RESULTS: Operative mortality was 9% in total; 7% in CABG, 5% in valve, 10% in CABG plus valve. Operative mortality was significantly higher in the urgent/emergency group than in the elective group (25% vs 6%). The actuarial survival rate for hospital survivors at 60 months after surgery was 75% and the mean survival period 76 months. There were no significant differences among operations. Preoperatively 81% of the patients had been in New York Heart Association class III or IV, and 88% of survivors were in class I or II in the late period. CONCLUSIONS: Early and late results for elective surgery in octogenarians are satisfactory. However, for urgent or emergent cases, there is a marked increase in morbidity and mortality.

Actuarial Analysis↗

PubMed2004

What influences the results in critical patients after cardiovascular surgery?

The predictive factors of surgical outcome were evaluated in compromised patients following cardiovascular surgery. Of 608 patients undergoing cardiovascular surgery between 1991 and 1999, 55 stayed in the intensive care unit for 2 weeks or longer. The mean age of these 55 patients was 56 years. There were 35 survivors and 20 nonsurvivors. Postoperative respiratory failure and gastrointestinal complications were significantly more frequent in those who died. The survival rate was significantly higher in patients who had enteral feeding compared to those who did not (88% versus 43%). Serum cholinesterase and total cholesterol concentrations were higher in the survivors. It was concluded that postoperative respiratory and gastrointestinal conditions influenced the surgical outcome, and serum cholinesterase and total cholesterol concentrations were valuable predictors of survival.

Adolescent↗

PubMed2004

Combination therapy for adult coronary artery aneurysm with off-pump coronary artery bypass grafting and vein graft-coated stent.

We report on a 51-year-old Japanese female with bilateral coronary artery aneurysms. Severe calcified aneurysms were detected in the proximal right coronary artery (RCA) and left anterior descending branch (LAD). The RCA was totally occluded and supplied by the blood flow via septal branches of the LAD. A two-stage management plan, including an off-pump coronary artery bypass grafting for the RCA with a right gastroepiploic artery and catheter angioplasty with an autologous vein graft-coated stent for the LAD, was successfully completed. Prophylactic treatments for coronary artery aneurysm are still controversial, therefore, minimal invasive procedures should be favored to prevent acute cardiac shock or sudden death related to aneurysmal obstruction.

Angioplasty, Balloon, Coronary↗

PubMed2004

A second mitral valve replacement in a patient with hereditary hemorrhagic telangiectasia (Osler's disease).

A 62-year-old female with Osler's disease was admitted to our hospital because of fever and cardiac failure. The patient had undergone a mitral valve replacement (MVR) using a Carpentier-Edwards prosthetic valve 14 years earlier. A bacterial examination of arterial blood identified Streptococcus mitis. No arteriovenous malformations were detected in visceral organs. The patient underwent MVR using the same prosthetic xenograft after conservative treatment and management of repetitive epistaxis and decayed teeth. Intra- and postoperative bleeding were typical of a mitral valve reoperation. This is the first reported experience, to the best of our knowledge, of a second MVR in a patient with Osler's disease.

Endocarditis, Bacterial↗