Biomedical subjects

S Ishimaru

Publications and source records attributed to S Ishimaru.

At least 19 recordsLinked to original sources

PubMed1999

CMS: an adapter molecule involved in cytoskeletal rearrangements.

Cas ligand with multiple Src homology (SH) 3 domains (CMS) is an ubiquitously expressed signal transduction molecule that interacts with the focal adhesion protein p130(Cas). CMS contains three SH3 in its NH2 terminus and proline-rich sequences in its center region. The latter sequences mediate the binding to the SH3 domains of p130(Cas), Src-family kinases, p85 subunit of phosphatidylinositol 3-kinase, and Grb2. The COOH-terminal region contains putative actin binding sites and a coiled-coil domain that mediates homodimerization of CMS. CMS is a cytoplasmic protein that colocalizes with F-actin and p130(Cas) to membrane ruffles and leading edges of cells. Ectopic expression of CMS in COS-7 cells resulted in alteration in arrangement of the actin cytoskeleton. We observed a diffuse distribution of actin in small dots and less actin fiber formation. Altogether, these features suggest that CMS functions as a scaffolding molecule with a specialized role in regulation of the actin cytoskeleton.

Adaptor Proteins, Signal Transducing↗

PubMed1999

Activation of the Drosophila C3G leads to cell fate changes and overproliferation during development, mediated by the RAS-MAPK pathway and RAP1.

The cellular signal transduction pathways by which C3G, a RAS family guanine nucleotide exchange factor, mediates v-crk transformation are not well understood. Here we report the identification of Drosophila C3G, which, like its human cognate, specifically binds to CRK but not DRK/GRB2 adaptor molecules. During Drosophila development, constitutive membrane binding of C3G, which also occurs during v-crk transformation, results in cell fate changes and overproliferation, mimicking overactivity of the RAS-MAPK pathway. The effects of C3G overactivity can be suppressed by reducing the gene dose of components of the RAS-MAPK pathway and of RAP1. These findings provide the first in vivo evidence that membrane localization of C3G can trigger activation of RAP1 and RAS resulting in the activation of MAPK, one of the hallmarks of v-crk transformation previously thought to be mediated through activation of SOS.

Amino Acid Sequence↗

PubMed1999

Successful surgical treatment of aortogastric fistula after an esophagectomy and subsequent endovascular graft placement: report of a case.

An aortogastric fistula is a rare but fatal complication after an esophagectomy and intrathoracic esophagogastric anastomosis. A 54-year-old man underwent an esophageal resection due to carcinoma in his lower esophagus. The alimentary tract continuity was restored by intrathoracic esophagogastric anastomosis. Forty-six days later, he suffered a massive hematemesis due to an aortogastric fistula which had formed at the esophagogastric suture line. The fistula was surgically obliterated twice, but each operation was followed by pseudoaneurysm formation. The patient was finally successfully treated with an endovascular stent graft placement. This is the first report of a patient surviving after developing this complication.

Anastomosis, Surgical↗

PubMed1999

Coronary revascularization with arterial conduits collateral to the lower limb.

A 62-year-old man with left main coronary artery disease had coronary artery bypass grafting. Angiography disclosed total occlusion of the left common iliac artery. The left internal thoracic artery and the left inferior epigastric artery were well developed as collateral pathways to the left external iliac artery. With concomitant femoro-femoral crossover bypass, these two large arterial conduits were harvested and grafted to the coronary artery.

Blood Vessel Prosthesis Implantation↗

PubMed1999

Endovascular stent graft repair of aortopulmonary fistula.

Two patients who had aortopulmonary fistula of postoperative origin with hemoptysis underwent successful repair by means of an endovascular stent graft procedure. One patient had undergone repeated thoracotomies two times, and the other one time to repair anastomotic aneurysms of the descending aorta after surgery for Takayasu's arteritis. A self-expanding stainless steel stent covered with a Dacron graft was inserted into the lesion through the external iliac or femoral artery. The patients recovered well, with no signs of infection or recurrent hemoptysis 8 months after the procedure. Endovascular stent grafting may be a therapeutic option for treating patients with aortopulmonary fistula.

Anastomosis, Surgical↗

PubMed1999

[Current appraisal of endoscopic thoracic sympathectomy: results of the national questionnaire surgery].

A questionnaire survey was performed in order to investigate the current status of endoscopic thoracic sympathectomy in Japan. Four hundred and twenty-nine (429) university, national or public hospitals with a minimum of 400 beds were included. A total of 248 of these hospitals responded. Among them 63 (25%) performed this procedure. The total of the cases was 1116. The number of access port and the technique for defunctioning the sympathetic chain were broadly divided into three methods. These methods were equally carried out among the departments. The clinical results were judged as satisfactory in the great majority of patients and the frequency of complications was low. On the other hand, the overall incidence of compensatory sweating remained relatively high and accumulated as the number of cases increased. But the reported frequency differed strikingly from hospital probably for lack of an objective way of quantifying following sympathectomy. Although overall complications were infrequent, the need for conventional thoracotomy to stop bleeding occurred in some cases. Therefore even this simple endoscopic operation demands the utmost surgical care, skill and experience. A few recurrences of preoperative symptoms were seen in the follow-up suggesting that all patients must be continually monitored after the operation.

Endoscopy↗

PubMed1998

The gene encoding dipeptidyl aminopeptidase BI from Pseudomonas sp. WO24: cloning, sequencing and expression in Escherichia coli.

We have isolated the dipeptidyl aminopeptidase BI (DAP BI) gene from the plasmid library of Pseudomonas sp. WO24 chromosomal DNA by the enzymatic plate assay using a chromogenic substrate. The DAP BI gene, designated dap b1, was further subcloned and sequenced. Sequence analysis of an approx. 3-kb fragment revealed an open reading frame of 2169 nucleotides, which was assigned to the dap b1 gene by N-terminal and internal amino acid sequences. The predicted amino acid sequence of DAP BI containing a serine protease Gly-X-Ser-X-Gly consensus motif displays extensive homologies to the several proteases belonging to the prolyl oligopeptidase family, a novel serine protease family possessing the catalytic triad with a specific array of Ser, Asp and His in this order, which is the hallmark of the member of this family including DAP IV. The dap b1 gene was expressed in Escherichia coli and the expressed enzyme was purified about 230-fold with 2.6% recovery from the cell-free extracts. The enzymatic properties such as molecular mass, substrate specificity and effect of inhibitor were similar to the native enzyme from Pseudomonas sp. WO24.

Amino Acid Sequence↗

PubMed1998

[Clinical results of acute closing aortic dissection].

The therapeutic outcomes of 43 patients with acute closing aortic dissection treated during the past 10 years were evaluated. The patients consisted of 30 men and 13 women with a mean age of 65 +/- 9 years. Ten were classified as Stanford type A, and the remaining 33 as type B. During follow-up (6 to 120 months; average 55 months), recanalization and an enlarged ulcer-like projection (ULP) were observed in 5 and 2 type a patients. Although recanalization was not observed in type B patients, enlarged ULP was observed in 10 of them, in 6 of whom developed aneurysm. During the follow-up period, ULP was observed at 30 sites in 26 patients. Monitoring the change in ULP over time showed that the ascending and the proximal descending aorta frequently tended to be enlarged and progressed to aorta frequently tended to be enlarged and progressed to aneurysm. Surgery was performed in 3 patients with recanalization, 5 with enlarged ULP, and 3 with atheroscloerotic aortic aneurysm. Although one patient died of cerebral complications, the other 10 patients showed favorable postsurgical courses. Among 8 patients who died, the actuarial survival rate was favorable, being 96, 91 and 83% at 1, 3 and 5 years. However, the survival rate free from complications related to aortic dissection, defined as rupture, ercanalization, enlarged ULP and aneurysmal change, was 78, 58 and 54% at 1, 3 and 5 years, indicating that aortic dissection-related complications are likely to develop within 3 years. This being the case, conservative therapy may be selected for closing aortic dissection when there are no serious complications in the acute phase. However, closely following patients with diagnostic imaging techniques is essential as there may be complications such as recanalization or enlarged ULP. Such complications should be surgically treated because they may affect long-term prognosis.

Aged↗

PubMed1998

[Postoperative changes in the coagulation and fibrinolytic systems in endoluminal stent-graft treatment of thoracic aortic aneurysms].

We studied changes in blood coagulation and fibrinolytic system in 18 cases of thoracic aortic aneurysm and 5 cases of aortic dissection treated with stent grafts. The mean operation time was 259 +/- 67 minutes and the amount of blood loss during operation was 472 +/- 456 ml. Although blood transfusion of 220 +/- 360 ml was performed in 7 cases, 16 of 23 cases (70%) received no homologous blood transfusion. Consequently, the endoluminal stent graft treatment was minimally invasive compared with the conventional surgical procedure. On the 1st postoperative day, platelet counts and AT-III decreased and TAT increased. The promotion of blood coagulability was found in these patients on the 1st day after the operation. Changes in the fibrinolytic system were less marked than that in coagulation. These results suggest that the thrombosed aneurysm was excluded from systemic blood flow by the stent graft. There was no consumption coagulopathy in any case with aneurysm excluded by stent graft deployment. Stent-graft treatment for thoracic aortic aneurysm can be successfully performed without consumption coagulopathy when the aneurysm is completely excluded.

Aged↗

PubMed1998

[Clinical results of endovascular stent graft repair for fifty cases of thoracic aortic aneurysms].

Between February 1995 and December 1997, 50 cases (55 lesions) of thoracic aortic aneurysms including 20 cases of aortic dissections were treated with an endovascular technique using the stent grafts. All patients were treated in the operating room under general anesthesia and the stent grafts were implanted through 18 Fr. or 20 Fr. sheaths via femoral arteries under fluoroscopic guidance. The stent graft was composed of several units of self-expanding stainless-steel Z stents covered with an ultra-thin polyester fabric. Stent graft deployment was technically successful in 53 of 55 lesions (delivery success rate: 96.4%). Exclusion of the aneurysms and entry closing without endoleak were achieved within two weeks after the operation in 43 of 53 lesions (initial success rate: 81.1%). Endoleak was found in 10 lesions (minor endoleak: 8 and major endoleak: 2 lesions). Two patients died in the periopertive period of delivery failures as injury to external iliac artery and damage to the delivery sheath caused by tortuous and narrow access routes. Endovascular stent graft repair of thoracic aortic aneurysms is minimally invasive operation in comparison with conventional surgical graft replacement with extracorporeal circulation. These early results suggest that the stent graft repair is possibly safe and useful treatment for the patients of thoracic aortic aneurysms especially in high risk patients. However, careful long-term follow-up is necessary to prove the value and the effects of this endovascular treatment and improvement of the stent graft system and technical training of endovascular surgery for operators are required to reduce the delivery failure and to determine the stent graft repair is reliable treatment.

Adult↗

PubMed1998

[Prediction of spinal cord ischemia with a retrievable stent graft on endovascular treatment for a case of thoracic aortic aneurysm].

Multiple aortic aneurysms in Behçet's disease were repaired with transluminaly placed endovascular stent grafts. Before deploying the stent graft device for permanent implantation for the saccular aneurysm located in the descending thoracic aorta, from which feeding arteries for the spinal cord possibly branched, a retrievable stent graft was inserted and evoked spinal cord potential (ESP) were monitored in order to predict spinal cord ischemia. The original retrievable stent graft, constructed of a self-expandable Z-shaped stainless steel stent covered with e-PTFE, can be easily withdrawn into a 18 Fr. sheath after deployment. Blood flow into intercostal arteries branching from that part of the descending aorta where the permanent stent graft is planned to be implanted, is intercepted by the retrievable stent graft. A change of ESP during the temporary implantation of the device indicates that spinal cord ischemia would be caused by permanent implantation of the stent graft. In this case, no change of ESP was observed and the patient showed no postoperative paraplegia. The retrievable stent graft was useful for prediction of spinal cord ischemia before endoluminal stent graft repair of the descending aortic aneurysm. However, the device is not flexible enough to fit a severely tortuous aorta, therefore we are obliged to select patients to some extent. Further improvement of the device is required to make prediction of spinal cord ischemia with the retrievable stent graft possible in all cases.

Aortic Aneurysm, Thoracic↗

PubMed1998

Unco-parahippocampectomy for direct surgical treatment of downward transtentorial herniation.

Downward transtentorial herniation is a major cause of death and disability caused by acute supratentorial mass lesions. Thirteen patients, 7 men and 6 women aged from 23 to 75 years old, with progressive transtentorial herniation caused by cerebral contusion with acute subdural haematoma, acute brain swelling after aneurysmal subarachnoid haemorrhage, or massive cerebral infarction were treated by direct surgery using selective removal of the uncus and parahippocampal gyrus (unco-parahippocampectomy). All patients showed progressive deterioration of transtentorial herniation (late third nerve stage or midbrain stage) with unilateral pupillary dilation and absent light reflex. Preoperative Glasgow Coma Scale scores ranged from 4 to 8. Unco-parahippocampectomy was performed via the middle temporal gyrus under the operating microscope. The oculomotor nerve, posterior cerebral artery, and midbrain were directly decompressed. Incision of the arachnoid membrane in the tentorial incisura allowed free communication of the cerebrospinal fluid between the supra- and finfra-cranial fossae to reduce the pressure gradient. Two of the 13 patients died (15%). Two of the 11 survivors (18%) were functionally independent and 1 (9%) required minimal assistance but was independent at home. This series suggests the lifesaving nature of unco-parahippocampectomy in patients with deteriorating clinical condition because of transtentorial herniation.

Adult↗

PubMed1998

Satigrel, a new antiplatelet agent, inhibits platelet accumulation in prosthetic arterial grafts.

BACKGROUND: Early and late vascular obstruction are both related to platelet adhesion and aggregation in the grafts. We assessed the effect of satigrel, a new oral antiplatelet agent, on the accumulation of indium-labeled platelets in knitted Dacron grafts inserted proximal to the femoral artery. METHODS: Nine patients with arteriosclerosis obliterans receiving grafts were treated with satigrel, and 10 others were enrolled as untreated controls. Scintigraphy was performed in postoperative weeks 2 and 4, and the ratio of the scintillation count of the graft to that of the native artery was calculated to assess platelet accumulation. RESULTS: In both weeks 2 and 4, the ratio was significantly smaller in the satigrel group than in the control group for the whole graft, the proximal anastomosis, and the distal anastomosis. CONCLUSIONS: Satigrel significantly inhibited platelet accumulation in vascular grafts and thus may be useful for preventing postoperative graft occlusion.

Aged↗

PubMed1998

Preliminary report on prediction of spinal cord ischemia in endovascular stent graft repair of thoracic aortic aneurysm by retrievable stent graft.

OBJECTIVE: To predict spinal cord ischemia after endovascular stent graft repair of descending thoracic aortic aneurysms, temporary interruption of the intercostal arteries (including the aneurysm) was performed by placement of a novel retrievable stent graft (Retriever) in the aorta under evoked spinal cord potential monitoring. METHODS: From February 1995 to October 1997, endovascular stent graft repair of descending thoracic aortic aneurysms was performed in 49 patients after informed consent was obtained. In 16 patients with aneurysms located in the middle and distal segment of the descending aorta, the Retriever was placed temporarily before stent graft deployment. The Retriever consisted of two units of self-expanding zigzag stents connected in tandem with stainless steel struts. Each strut was collected in a bundle fixed to a pushing rod, and the stent framework was lined with an expanded polytetrafluoroethylene sheet. The Retriever was delivered beyond the aneurysm through a sheath and was retracted into the sheath 20 minutes later. A stent graft for permanent use was deployed in patients whose predeployment test results with the Retriever were favorable. Evoked spinal cord potential was monitored throughout placement of the Retriever and stent grafting until the next day. RESULTS: The Retriever was placed in 17 aneurysms in 16 patients. There were no changes in amplitude or latency of evoked spinal cord potential records obtained before or during Retriever placement. After withdrawal of the Retriever, all aneurysms were excluded from circulation immediately after permanent stent grafting. There were no changes in evoked spinal cord potential, nor were neurologic deficits seen after stent graft deployment in any patient. CONCLUSIONS: These results suggest that predeployment testing with the Retriever under evoked spinal cord potential monitoring is promising as a predictor of spinal cord ischemia in candidates for stent graft repair of thoracic aortic aneurysms.

Aged↗

PubMed1998

Effect of coacervated alpha-elastin on proliferation of vascular smooth muscle and endothelial cells.

The arterial wall injury associated with arterial graft implantation causes smooth muscle cells (SMCs) in the media to migrate and proliferate in the intima at the graft-artery junction resulting in anastomotic intimal hyperplasia (AIH). An important step in developing a small-diameter prosthesis may be to stimulate endothelialization and thereby inhibit AIH. In this study, we investigated the effect of coacervated and crosslinked alpha-elastin on proliferation of SMCs and endothelial cells (ECs) in vitro. Coacervation is an important step in the conversion of proelastin to make an elastin fiber in vivo. SMCs and ECs were prepared from porcine aortic media and endothelium, respectively. SMCs and ECs (three to five passages, 4 x 10[4] cells/well) were seeded onto 12 well plates, coated and crosslinked with 0 or 10 mg/mL of coacervated alpha-elastin. After the 1st, 2nd, or 3rd day of cultivation, proliferation was assayed by scintillation counting of [3H]-thymidine incorporation. For the 4th day only, 0, 0.1, 1, 10 mg/mL concentration of coacervated alpha-elastin was coated and crosslinked. SMC proliferation (1st, 2nd day: p<0.005; 3rd, 4th day: p<0.0001) was significantly inhibited over time and dose dependently, eg, 0.1 mg/mL (45.7+/-2.3%: % of control p<0.005), 1 mg/mL (5.9+/-0.7%, p<0.0005), 10 mg/mL (2.8+/-0.4%, p<0.0005). EC proliferation was inhibited over time by 10 mg/mL of coacervated alpha-elastin (2nd, 3rd day: p<0.005; 4th day: p<0.0001), but proliferation (132.8+/-9.9%: % of control p=NS) was stimulated by 0.1 mg/mL of coacervated alpha-elastin. These results suggest that coating and crosslinking a coacervated alpha-elastin into the structure of arterial prosthesis may inhibit AIH and stimulate endothelialization.

Alkanesulfonic Acids↗

PubMed1998

Quantitative kinetic analysis of blood vessels in the outer membranes of chronic subdural hematomas.

Dynamic biologic modeling was used to calculate the transfer rate constant for gadolinium-diethylenetriaminepenta-acetic acid (Gd-DTPA) and capillary permeability in the outer membrane of chronic subdural hematomas and effusions. Following intravenous Gd-DTPA injection, Gd concentrations in the subdural fluid and in timed arterial blood samples were measured by ion-coupled plasma emission spectrometry in 53 chronic subdural hematomas and 18 chronic subdural effusions. The capillary surface area in outer membrane was assessed morphometrically. Transfer rate constants for subdural hematomas and subdural effusions were 12.4 +/- 1.0 and 20.6 +/- 1.7 (x 10(-4)min-1, respectively. Capillary permeabilities for subdural hematomas and subdural effusions were 16 +/- 1.2 and 19 +/- 3.7 ml.min-1(mm2/mm3)-1, respectively. The capillary surface areas for subdural hematomas and subdural effusions were 48 +/- 3 and 77 +/- 10 mm2/mm3, respectively. The high degree of infiltration of Gd into subdural effusions reflects the high capillary surface area in the outer membrane rather than greater permeability of individual capillaries. The value of transfer rate constant was correlated inversely with the duration of the chronic subdural fluid collection. Immature outer membrane has a high transfer rate constant which allows extravasation of plasma components into the subdural space, resulting in increasing volume of the subdural effusion. Delayed magnetic resonance imaging following Gd administration may be clinically useful for estimating the age of chronic subdural fluid accumulations.

Aged↗

PubMed1998

Selective targeting and photodynamic destruction of intimal hyperplasia by scavenger-receptor mediated protein-chlorin e6 conjugates.

BACKGROUND: Photosensitizers, such as Photofrin II or Chloroaluminum-sulfonated phthalocyanine accumulate at sites of arterial injury. We have exploited this property to develop a model of photodynamic therapy (PDT) for intimal hyperplasia. The fluorescent probe [maleylated-bovine serum albumin (mal-BSA) conjugated with Texas-red] can be selectively targeted to intimal macrophages and smooth muscle cells recruited during formation of hyperplasia via a receptor-mediated mechanism. METHODS: In this study, the photosensitizer chlorin e6 (Cle6) was conjugated to mal-BSA in a rat model of intimal hyperplasia, then tested the efficacy of the ligand conjugation to photosensitizer (mal-BSA/Cle6) in PDT of intimal hyperplasia. Arterial wall injury was produced by a balloon catheter pulled through the abdominal aorta of the rat to create a model of intimal hyperplasia. Fluorescent compounds were injected two weeks after injury. RESULTS: Four hours after injection, the intensity of fluorescence achieved with injection of mal-BSA/Cle6 was higher for intimal hyperplastic lesions as compared to control areas. BSA-Cle6 unconjugated did not demonstrate such delivery. Two weeks after balloon injury, the injured aorta was irradiated externally with an argon pumped dye laser four hours following the photosensitizer injection. We employed two total radiant exposures: 20 J/cm2 and 40 J/cm2. Forty-eight hours after PDT, the arteries were examined histologically. Intimal hyperplastic cells were significantly reduced by PDT in the mal-BSA/Cle6 injected group (40-100%) versus the Cle6 group (0-20%). CONCLUSIONS: Mal-BSA/Cle6 is taken up efficiently by a scavenger pathway, localizes in areas of intimal hyperplasia, and functions as a photosensitizer for PDT.

Animals↗

PubMed1997

Healing mechanisms of high-porosity PTFE grafts: significance of transmural structure.

A high-porosity structure facilitates endothelialization of polytetrafluoroethylene (PTFE) grafts. The mechanism for endothelial coverage, however, has been controversial. This study was designed to clarify the healing mechanisms of high-porosity PTFE grafts. Four types of PTFE grafts (n = 48) were studied after implantation in both carotid and femoral arteries of dogs. The grafts were standard (ST) PTFE [mean internodal distance (MID): 30 microm]; high-porosity (HP) PTFE (MID 90 microm), composite porosity (CP) PTFE (MID: inner layer, 90 microm; outer layer, 30 microm); and polyurethane-coated high-porosity (PCHP) grafts which had the outer surface covered with nonporous polyurethane. Patency rates at 18 weeks were ST 6/12, HP 8/12, CP 6/12, and PCHP 3/12 (P = 0.290). The rates of endothelialization (%, mean +/- SD) in the patent grafts were ST 25 +/- 7, HP 75 +/- 20,* CP 57 +/- 15,* and PCHP 17 +/- 5 (*P < 0.05 vs ST or PCHP). Rich transmural tissue incorporation was observed in the HP grafts. In contrast to the HP grafts, PCHP grafts had no outer tissue ingrowth, inner tissue incorporation was scant, and anastomotic intimal hyperplasia was pronounced. The edges of pannus ingrowth in the PCHP grafts were irregular, such that the anchoring of pannus was weak and easily detachable. Well-developed endothelial cells were observed in the HP and CP grafts, but nonendothelialized areas always occurred in the center of the grafts. Capillary openings were noted in the HP grafts; however, their number was small (0-8/graft) on electron microscopy and did not account for the degree of endothelialization observed. We conclude that the principal mechanism for endothelialization of PTFE grafts is ingrowth from the anastomoses rather than transmural endothelialization, even in high-porosity grafts. Transmural fibrocapillary incorporation of PTFE vascular grafts provides a key supporting structure essential to the progression and attachment of endothelial ingrowth from the anastomoses.

Animals↗