Biomedical subjects

S Ishimaru

Publications and source records attributed to S Ishimaru.

At least 19 recordsLinked to original sources

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

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↗

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↗

PubMed1997

Blood volume and flow velocity through parenchymal microvessels in ischemic brain edema of rats.

Focal cerebral ischemia was produced in rats with left middle cerebral artery occlusion for 24 hours. Regional CBF was measured by the 14C-iodoantipyrine technique. The distribution of red blood cells (RBC) and plasma in cerebral microvessels was determined by radioluminography using 51Cr-RBC and 125I-bovine serum albumin, respectively. The mean transit times of RBC and plasma, blood volume, and hematocrit were calculated. The water content was measured by specific gravity. The blood flow was reduced to 2% of the control value in the central core, where the brain edema was the most severe. The blood volume decreased to 25% and the mean transit times of RBC and plasma increased about tenfold. In the outer periphery, where CBF was reduced to 39% but brain edema was not induced, the blood volume was decreased to 76% while the mean transit time of RBC was increased 2.1-fold, being greater than the increase in the plasma transit time. These findings indicate that focal ischemia has variable effects on the blood volume and flow velocities of RBC and plasma in the parenchymal microvessels depending on the depth of blood flow and edema. A decrease in blood flow is probably related to a reduction in the flow velocities of RBC and plasma in the surrounding ischemic tissue rather than to decreased number of perfused capillaries in the ischemic core.

Animals↗

PubMed1997

Inhibitory effect of type 1 collagen gel containing alpha-elastin on proliferation and migration of vascular smooth muscle and endothelial cells.

The purpose of this study was to investigate in vitro the potential effect of type 1 collagen gel containing alpha-elastin on the proliferation of vascular smooth muscle cells and vascular endothelial cells, and on smooth muscle cell migration. Vascular smooth muscle cell and endothelial cell were cultured in 12-well plates precoated with collagen gels and alpha-elastin. Cell proliferation rates were measured by monitoring [3H]-thymidine incorporation. After 2, 3 or 4 days of culture, the proliferation rate of both smooth muscle cells and endothelial cells was significantly decreased on collagen gel containing 10 mg/ml alpha-elastin compared with collagen gel only as control. Smooth muscle cell proliferation on collagen gel containing alpha-elastin on the 4th day of culture was decreased dose-dependently, e.g. 1 mg/ml of alpha-elastin (74.8(2.3)% of control, P=n.s.); 5 mg/ml (56.7(2.1)%; P<0.05); 10 mg/ml (30.3(3.1)%; P<0.005). In the case of cultured endothelial cells, however, [3H]-thymidine incorporation was not decreased significantly in the presence of 5 mg/ml alpha-elastin (83.1(7.9)%, P=n.s.). After stimulation by platelet-derived growth factor, the smooth muscle cell migration rate on collagen gel containing alpha-elastin (5 mg/ml) was decreased over time. The area of migration on the 6th day of culture was also significantly decreased dose-dependently in the presence of alpha-elastin, e.g. 1 mg/ml (72.6(3.4)% of control, P<0.05), 5 mg/ml (56.9%(1.5)%; P<0.05); 10 mg/ml (37.3(2.7)%; P<0.0005). In conclusion, alpha-elastin inhibited the proliferation and migration of smooth muscle cell in a dose-dependent manner on collagen gel culture, however, at high concentrations of alpha-elastin (10 mg/ml), the endothelial cell proliferation rate was also inhibited. At 5 mg/ml, alpha-elastin significantly inhibited smooth muscle cell proliferation and migration but did not significantly inhibit endothelial cell proliferation. Incorporation of collagen gel containing alpha-elastin into the structure of arterial prosthesis offers the possibility of inhibiting smooth muscle cell hyperplasia without significant effect on endothelial cell formation.

Animals↗

PubMed1997

Thallium-201 single photon emission computed tomography imaging of meningioma cells in hyperostosis.

Hyperostosis is a well-known bony reaction associated with meningioma. However, it is difficult to determine preoperatively whether meningioma cells have invaded the bone, and if so, the extent of tumor invasion. Preoperative thallium-201 chloride single photon emission computed tomography (201Tl SPECT) was performed in four patients with meningioma and hyperostosis. The presence of meningioma cells in bone biopsy specimens was also investigated using standard histological techniques. 201Tl SPECT revealed increased uptake in three of the four patients. Biopsy specimens from these three patients revealed invasion of the bony lesions by meningioma cells in accordance with the 201Tl SPECT findings. 201Tl SPECT found no abnormal uptake in the other patient, in which there was also no histological evidence of tumor invasion of bone. Preoperative 201Tl SPECT can provide information on bone invasion by meningioma, which will facilitate preoperative planning of the extent of bony resection required at meningioma surgery.

Adolescent↗

PubMed1997

[Stent graft treatment for two cases of DeBakey IIIb dissecting aortic aneurysm].

Two patients with DeBakey IIIb dissecting aortic aneurysms were treated with transluminally placed endovascular stent grafts. Surgery was required for both patients because the false lumens were not thrombosed for several months. Stent graft devices composed of several units of self-expandable Z stents covered with ultra-thin woven Dacron were inserted through 18 Fr sheathes via femoral arteries. The stent grafts were deployed successfully and blood flow into the false lumens was reduced immediately and finally thrombosed without blood leakage from the entries. The endoluminal stent graft treatment is minimally invasive operation in comparison with former surgical operations, and is useful for aortic aneurysms especially in high risk patients. However, improvement of the stent graft devices, including the delivery systems such as the dilator, sheath and pushing rod, which are incomplete, and developing better devices, is required to reduce delivery failure and to make the stent graft treatment more reliable.

Aged↗

PubMed1997

[New method for closure of median sternotomy: usefulness of barbed staple].

In this report, 15 cases using straight staple (group A) and 35 cases using barbed staple (group B) were compared for the purpose of investigating efficacy for median sternal closure. The staples were placed by a Stapilizer powered metaphyseal staple system following partial transsternal fixation with two wires. As a means of assessing the status of back out, which is a major cause of poor fixation, the back out rate (BOR) was measured on lateral sternal radiographies. The average BOR was found to be 33.8% in group A and 21.2% in group B (p < 0.001). Barbed staples seemed to be more useful for sternal fixation than straight staples. This method of applying barbed staples had the advantages of speed, ease of insertion and noninvasion of the retrosternal region. It should be recommended in cases with severe adhesion of the retrosternal region after coronary operation.

Adult↗

PubMed1996

Immunocytochemical detection of p53 protein from pancreatic duct brushings in patients with pancreatic carcinoma.

BACKGROUND: It is often difficult to distinguish pancreatic carcinoma preoperatively from chronic pancreatitis. Therefore, we have developed a new method of detecting p53 immunoreactivity in cytologic material obtained by endoscopic retrograde pancreatic duct brushing (ERPDB). METHODS: Twenty-eight patients with prominent strictures of the main pancreatic duct demonstrated by pancreatography including 20 ductal cell carcinoma and 8 chronic pancreatitis were studied. The ability to distinguish between these two groups preoperatively by conventional cytologic examination was compared with p53 immunocytochemistry using ERPDB: RESULTS: The sensitivity, specificity, and overall accuracy of conventional cytologic examination in distinguishing ductal cell carcinoma from chronic pancreatitis were 60%, 100%, and 71% respectively. In comparison, the sensitivity, specificity, and overall accuracy of p53 immunocytochemistry in distinguishing were 90%, 100%, and 93%, respectively. The sensitivity of p53 staining of specimens from patients with carcinoma of the body or tail of the pancreas (90%) was the same for those with tumors of the head of the pancreas (90%). CONCLUSIONS: These results suggest that p53 immunocytochemistry using ERPDB in conjunction with conventional cytologic examination can help differentiate ductal cell carcinoma from chronic pancreatitis preoperatively.

Adenocarcinoma↗

PubMed1996

Pathology and cellular kinetics of gallbladder with an anomalous junction of the pancreaticobiliary duct.

OBJECTIVES: Anomalous junction of the pancreaticobiliary duct (AJPBD) is thought to be an important risk factor for gallbladder carcinoma in Japan. In this report, we examine histopathology and cellular kinetics of gallbladder mucosae of patients with AJPBD and the possible risk of gallbladder carcinoma. METHODS: We examined 62 gallbladders from patients with AJPBD (group A), 16 gallbladder carcinomas from patients with AJPBD (group B), 60 gallbladder carcinomas from patients without AJPBD (group C), and six normal gallbladders from patients without AJPBD (group D). Histopathology, mucosal heights, and proliferative cell nuclear antigen-labeling index were obtained from routinely processed tissue specimens. RESULTS: The incidence of hyperplastic changes in group A and in the noncancerous regions (NCRs) of group B was greater than in the NCRs of group C (p < 0.05). The incidence of dysplastic changes in the NCRs of group B was greater than in the NCRs of group C (p < 0.05). The mucosal heights in group A and in the NCRs of group B were higher than in the NCRs of group C (p < 0.05). A high proliferative cell nuclear antigen-labeling index was observed in group A and in the NCRs of group B, where hyperplastic changes were frequently observed. CONCLUSIONS: These results suggest that a sequence of hyperplastic changes with a corresponding increase in cellular kinetics with progression through dysplasia to carcinoma may be important in carcinogenesis in gallbladders of patients with AJPBD. AJPBD itself may be a possible risk for gallbladder carcinoma.

Adolescent↗

PubMed1996

Platelet-activating factor and arachidonic acid metabolites in psoriatic inflammation.

Platelet-activating factor (PAF), as well as PAF acetylhydrolase (PAF-AH) activity in the peripheral blood plasma of patients with psoriasis and palmoplantar pustolosis, was measured with a radioimmunoassay technique, and compared with leukotriene (LT) B4, LTC4, LTD4 and E4 (LTD4/E4), thromboxane (TX) B2 and prostaglandin (PG) E2 levels. In a normal healthy group (n = 12) PAF level was 25.9 +/- 6.5 pg/0.1 ml plasma (mean +/- standard error of the mean: SEM), and this was elevated in patients with psoriasis (68.1 +/- 11.8, n = 25, P < 0.01), without a change in the PAF-AH level. LTB4 showed a similar increase (115.0 +/- 21.6 pg/ml vs. 68.2 +/- 11.8 pg/ml, P < 0.05), while TXB2 and PGE2 showed insignificant (P > 0.05) changes. LTC4 and LTD4/E4 were around the level of the limit of detection. Patients with palmoplantar pustulosis (n = 33) demonstrated similar, but milder and statistically insignificant, increases in PAF, LTB4, TXB2 and PGE2 levels. Modulation of the mediator levels before and after treatment was compared in 16 patients with psoriasis and 11 with palmoplantar pustulosis. PAF in psoriasis significantly decreased after treatment (70.9 +/- 17.1 to 25.1 +/- 5.5, P < 0.05) and this was moderately correlated (r = 0.298) with clinical improvement as indicated by the psoriasis area and severity index (38.5 +/- 7.5 to 10.9 +/- 4.2, P < 0.01). TXB2 (180.2 +/- 100.4 to 34.1 +/- 13.5), PGE2 (3.7 +/- 0.7 to 2.9 +/- 0.5) and LTB4 (120.1 +/- 31.1 to 84.2 +/- 8.2), in psoriasis, mildly decreased without statistical significance. Patients with palmoplantar pustulosis demonstrated a similar decrease in all mediators without statistical significance. The results obtained suggest a role of PAF in psoriasis. As the priming effects of PAF have been shown, for leucocytes and endothelial cells, to enhance their inflammatory response, we assume that PAF has roles in the acute phase of psoriatic and leucotactic inflammation.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

PubMed1996

[Blood coagulation disorders observed in arteriosclerosis obliterans].

Activated platelet function indicated by beta-TG and PF4 is observed in the patients from arteriosclerosis obliterans (ASO) with severe disturbance of peripheral circulation. Increase in FpA, TAT, FDP and PIC suggest that blood coagulation and fibrinolysis are accelerated. Fibrinolysis might be activated in response to thrombus formation in screlotic peripheral artery. It is suggested that antiplatelet and/or anticoagulation therapy is acceptable for ASO with disorders of blood coagulation and fibrinolysis. Adequate antithrombotic therapy is necessary not only to treat ASO but also to prevent progression of arterioscrelosis. It is important to recognize harmful influence of antithrombotic therapy (antiplatelet, anticoagulation or thrombolysis) on blood coagulation and fibrinolysis, on the patient being canditate for vascular surgery.

Arteriosclerosis Obliterans↗

PubMed1996