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Biomedical subjects

T Iwai

Publications and source records attributed to T Iwai.

At least 19 recordsLinked to original sources

Application of chimerism-based drug-induced tolerance to rat into mouse xenotransplantation.

The current critical shortage of human donor organs has stimulated the feasibility of the xenogenic transplantation, such as swine to primate. We have previously reported the induction of donor-specific tolerance in MHC-disparated recipient mice by using our cyclophosphamide (CP)-induced tolerance conditioning. In this study, we examined the efficacy of our CP-induced tolerance conditioning in xenogenic transplantation model. F344 rats and B10 mice were used as donors and recipients. Recipient mice were treated with donor spleen cells, CP, Busulfan and bone marrow cells, with or without prior NK-cell depletion. Donor mixed chimerism, and the presence of donor reactive T-cell population were analysed by flow cytometry. The survival of the donor skin grafts were observed after the conditioning. Donor mixed chimerism was temporary induced but terminated at 10 weeks after treatments. Donor-specific prolongation of the skin graft survival was observed after the treatments, however, grafts were rejected in the long term. NK-cell depletion, prior to the treatments, did not affect the levels of the mixed chimerism or graft prolongation. The donor-reactive recipient T-cell population was remained the same level as the untreated mice, suggesting the failure of the induction of the central T-cell tolerance. Thus, partial efficacy of our CP-induced tolerance treatments in the rat to mice xenotransplantation was observed. Our results suggested that the additional treatments were required to establish the stable xenogenic tolerance.

Animals↗

Effect of low-density lipoprotein apheresis on patients with peripheral arterial disease. Peripheral Arterial Disease LDL Apheresis Multicenter Study (P-LAS).

AIM: The effectiveness of low-density lipoprotein (LDL) apheresis for patients with peripheral arterial disease (PAD) was investigated to confirm a hypothesis based on subjective evidence that the amelioration of blood rheology would be the most contributing factor for improvement in clinical symptoms. Evaluation of the severity of intermittent claudication is difficult because of the lack of an accurate parameter to assess muscle ischemia during exercise, thus we objectively evaluated by non-invasive near-infrared spectroscopy (NIRS) on a treadmill in this study. METHODS: Thirty-one patients with PAD were evaluated for hemostatic function and physiological parameters such as ankle-brachial pressure index (ABI), maximum tolerated walking distance (MTWD) and recovery time (RT) or recovery ability index (RAI) on NIRS. Laboratory tests included plasma assays of total cholesterol, LDL-cholesterol, high-density lipoprotein (HDL) cholesterol, triglyceride, and fibrinogen. The change in red-cell filtration rate was evaluated for the improvement of microcirculation. Statistical analysis was performed using the paired Student's t-test with Bonferroni's correction. RESULTS: A significant improvement in ABI and MTWD was observed after average 9.6+/-0.8 sessions of LDL apheresis treatment and the amelioration of microcirculation in ischemic muscle was objectively evaluated as significant improvement in RAI on NIRS. Rest pain was improved in all 5 patients with Fontaine's classification III or IV. A severe ulcer refractory to usual medications was dramatically diminished in the area by 10 sessions of LDL apheresis and fully healed 5 months after the final LDL apheresis treatment followed by medication. No angiographical change was observed in the arterial occlusive lesions in any patients. CONCLUSIONS: The effectiveness of LDL apheresis on the improvement in physiological parameters such as ABI, MTWD and clinical symptoms in patients with PAD was confirmed. The severity of intermittent claudication was objectively evaluated using non-invasive NIRS. The RT or RAI was useful parameter to evaluate the improvement in the ischemic symptoms of the extremities.

Aged↗

Treatment of three pancreaticoduodenal artery aneurysms associated with coeliac artery occlusion and splenic artery aneurysm: a case report and review of the literature.

A case of three pancreaticoduodenal artery (PDA) aneurysms associated with coeliac artery occlusion and a concomitant splenic arterial aneurysm is described. Surgical treatment was used because it was anticipated that the hepatic blood supply would be obstructed completely if percutaneous transluminal embolization for three PDA aneurysms were performed. Splenectomy in continuity with the splenic artery aneurysm and PDA aneurysmectomies were performed, and infrarenal abdominal aorto-splenic artery bypass was accomplished using a 6mm ringed expanded polytetrafluoroethylene graft. The postoperative course was uneventful. Graft patency and successful aneurysm ablation were confirmed using MRA and intravenous DSA. Arterial histology revealed segmental arterial mediolysis. At 2-year follow-up, the patient was well and asymptomatic. A literature review of PDA aneurysms is presented.

Aneurysm↗

Characteristics of peripheral microembolization during iliac stenting: Doppler ultrasound monitoring.

OBJECTIVE: To evaluate the characteristics of distal microembolic signals (MES) during iliac stenting using Doppler ultrasound monitoring. DESIGN: Prospective clinical study. METHODS: A 2-MHz probe was used to monitor continuously at the ipsilateral tibioperoneal trunks during technically and hemodynamically successful iliac stenting in 10 patients without infrainguinal occlusive lesion. MESs at guide-wire, balloon, or stent crossing (phase 1), predilatation (phase 2), stent deployment (phase 3), postdilatation (phase 4), and contrast medium or heparinized saline injection (at injection) were analyzed. Differentiation of gaseous emboli from particulate emboli was achieved by calculation of the sample volume length. RESULTS: No distal embolic complications were observed. Five hundred and forty-one MESs were detected. The MES incidence and intensity in phase 3 were significantly higher than those in phase 1, phase 2, and phase 4 (p<0.05). The MES intensity at injection was significantly higher than that in each of four phases (p<0.0001). CONCLUSIONS: Both the MES incidence and intensity were highest at stent deployment. Further study is required of microembolism during endovascular procedures in the lower extremities.

Aged↗

Efficacy and limitations of cyclophosphamide-induced tolerance against alphaGal antigen.

In the present study, we have elucidated the efficacy of two cyclophosphamide (CP)-induced tolerance protocols for the induction of B-cell tolerance against Galalpha1-3Galbeta1-4GlcNAc (alphaGal) antigens. alpha1,3-galactosyltransferase-deficient (GalT-/-; H-2(b/d)) mice received with 1 x 10(8) AKR (alphaGal+/+ H-2k) spleen cells (SC) followed by 200 mg/kg CP, or alternatively followed by 200 mg/kg CP, 30 mg/kg Busulfan (BU) and 1 x 10(8) T-cell-depleted AKR bone marrow cells (BMC). The generation of both anti-alphaGal and anti-donor antibodies were completely suppressed, but normal antibody production against third party antigens was observed after BALB/c skin grafting in both groups of GalT-/- mice. In GalT-/- mice, treated with SC and CP, mixed chimerism was not observed. Cellular rejection was observed in grafted donor AKR hearts with an absence of humoral rejection, whereas humoral rejection was observed in untreated GalT-/- mice. On the other hand, long-term mixed chimerism and permanent acceptance of donor AKR skin graft and heart graft were achieved in GalT-/- mice treated with SC, CP, BU and BMC. These results demonstrate the efficacy of classical drug-induced tolerance in the induction of B-cell tolerance against alphaGal antigens. However, induction of stable mixed chimerism was required for the suppression of cellular rejection.

Animals↗

[Two-stage repair of the transposition of great arteries with interruption/coarctation of the aorta].

We report on 10 patients who underwent two-stage repair of transposition of the great arteries (TGA) with interruption (IAA) or coarctation (CoA) of the aorta. First, an operation for aortic arch reconstruction was performed: Blalock-Park with pulmonary artery banding (PAB) for IAA (5 patients), subclavian flap with PAB for CoA (4 patients) and end-to-end anastomosis without PAB (1 patient). All survived the first operation and had no significant pressure gradient with good growth of the ascending aorta, except for the 1 case without PAB. Half of the 8 patients who underwent PAB developed migration of the PAB. The arterial switch operation (ASO) was performed 0.7-12.6 (5.6+/-4.7) months after the first surgery. One patient with an abnormal coronary artery tract was lost after ASO. Five developed pulmonary artery stenosis and 1 developed supra-aortic stenosis late after ASO. Two patients need reoperation, 1 for supra-aortic stenosis, and the other for reCoA. Two-stage repair for TGA with IAA/CoA is still a useful method with a good operative result. However, strict follow-up is necessary because of the high frequency of late morbidity.

Aorta, Thoracic↗

Detection and localization of periodontopathic bacteria in abdominal aortic aneurysms.

OBJECTIVES: We examined a possible link between periodontal disease and abdominal aortic aneurysm (AAA) by studying resected aneurysmal specimens from AAA patients for the presence of periodontopathic bacteria. DESIGN: Prospective case control study. MATERIAL AND METHODS: Thirty-two AAA patients were enrolled in the study. Periodontitis was classified according to the probing depth of periodontal pocket. Thirty-two aneurysmal walls, 16 mural thrombi, 5 atherosclerotic occlusive aorta and 5 control arterial tissue, were examined for 7 periodontal bacteria using polymerase chain reaction (PCR) method. The localization of the bacteria in the aneurysmal/atherosclerotic wall was determined by thromboendarterectomy. RESULTS: All patients had periodontal disease, and most cases were severe. PCR examination of the aneurysmal specimens showed that 86% were positive for periodontal bacterial DNA. No bacteria were detected in the control specimens. The bacteria were found in both the intimal/medial layer and the adventitial layer of the aneurysmal wall but only in intimal/medial layer of the atherosclerotic occlusive aorta. CONCLUSION: Periodontopathic bacteria were present in a high percentage of specimens of diseased arteries from AAA patients and were found throughout the whole aneurysmal wall. These bacteria may play a role in the development of AAAs and/or contribute to weakening the aneurysmal wall.

Aged↗

Treatment strategy for Boerhaave's syndrome.

Esophageal rupture is a potentially mortal condition. Rapid and correct diagnosis, and urgent surgical treatment with esophagectomy is indicated, but conservative and other surgical treatments have also been reported recently. The treatment strategies for esophageal rupture are discussed here, based on our experiences with four cases during the last 10 years. They were admitted urgently and each was treated by a different method. Three of them underwent emergency operations, one undergoing primary closure of the ruptured esophagus, another received a T-tube insertion from the ruptured site with omental flap, and the third an esophagogastrectomy. The fourth case was treated conservatively. All patients survived and were discharged 36-144 days post treatment. One of them was readmitted for debridement of necrotic rib. In conclusion, the prompt and accurate diagnosis of esophageal rupture is crucial for a subsequent successful treatment. Conservative treatment or operation including esophagectomy will be determined by the severity of the condition.

Adult↗

Development and clinical application of semi-loop-shaped retractor for gasless laparoscopic surgery.

BACKGROUND: Gasless laparoscopy has the advantage of avoiding the risk inherent in pneumoperitoneum, but has not gained widespread popularity because of limited exposure of the operative field. Improved retraction devices are therefore needed. METHODS: A loop-shaped metallic retractor was designed for planar lifting of the anterior abdominal wall. Four types of retractor (5/6-, 3/4-, and 1/2-circle with rod at 90 degrees, and 1/2-circle with rod at 97 degrees ) were studied in 15 pigs. The device was then used for 47 patients. RESULTS: The 1/2-circle was the most smoothly inserted retractor and was significantly safer than the 5/6-circle (p < 0.05, Fisher's exact probability test). The 1/2-circle with rod at 97 degrees was utilized for clinical cases. This retractor can be readied within 1 min and was used successfully for all operations. CONCLUSIONS: This new retractor for gasless laparoscopic surgery provides good exposure and has the potential to enhance the performance of advanced laparoscopic surgery.

Abdominal Wall↗

Evaluation of buttock claudication with hypogastric artery stump pressure measurement and near infrared spectroscopy after abdominal aortic aneurysm repair.

OBJECTIVE: We explored the usefulness of intraoperative measurement of hypogastric artery (HGA) stump pressure (HGA-SP) and postoperative near infrared spectroscopy (NIRS) in evaluating buttock claudication (BC) after abdominal aortic aneurysm (AAA) repair. DESIGN: Retrospective clinical study. PATIENTS AND METHODS: Twenty patients who were undergoing AAA repair were enrolled. The HGA was ligated bilaterally in 5 patients, unilaterally in 12, and preserved in 3. The HGA-SP was measured intraoperatively. Postoperatively, NIRS was used to evaluate buttock muscle ischemia during walking. RESULTS: Six patients had unilateral and 1 bilateral BC after AAA repairs. The median HGA-SP brachial pressure index (HBI) was 0.62 (range: 0.45-0.64) in 8 claudicating buttocks and 0.76 (range: 0.63-0.90) in 13 asymptomatic buttocks (p < 0.0005). The HBI was <0.65 in all claudicating buttocks, whereas it was >0.63 in asymptomatic buttocks. In all 8 claudicating buttocks, NIRS showed the ischemic pattern with recovery time lasting more than 240 s. CONCLUSIONS: An HBI below 0.65 may be a predictor of BC after AAA repair. NIRS appears to be a useful noninvasive method for evaluating BC after AAA.

Aged↗

A case of cancer on the pharyngoesophageal junction treated by ambulatory endoscopic mucosectomy.

A 52-year-old man underwent endoscopy because of discomfort in the hypopharyngeal region, and a 1.5-cm tumor was found on the pharyngoesophageal junction. In 1992, the patient was treated for advanced cervicothoracic esophageal cancer by preoperative chemotherapy and esophagectomy with radical lymph adenectomy and right thoracotomy. Reconstruction with a gastric substitute by cervical esophagogastrostomy was performed and postoperative adjuvant radiotherapy followed. Histologically, the esophageal tumor had invaded the adventitia and showed metastases to regional lymph nodes and vascular involvement with a free surgical margin. Hypopharynx was also included in the irradiation field. Therefore, we tried to resect another primary tumor on the pharyngoesophageal junction by the endoscopic mucosectomy technique with an esophageal multipurpose tube (np-EEM). The tumor was resected on August 21, 1996, but follow-up endoscopy revealed residual or another primary tumor on the pharyngoesophageal junction in October 1996. The first resected specimen revealed a positive cut margin that might indicate incomplete resection. Three months later we performed a second mucosectomy. No problems occurred during or after tumor resection. Both treatments were performed without hospitalization, and the patient returned to his normal daily life on the day following tumor resection. Follow-up examinations have shown no sign of cancer recurrence on the pharyngoesophageal junction for more than 4 years.

Ambulatory Surgical Procedures↗

Activation of human T cells with NK cell markers by staphylococcal enterotoxin A via IL-12 but not via IL-18.

We have reported recently that mouse liver NK cells and NK1 x 1+ T cells were activated by bacterial superantigens via the IL-12 production from Kupffer cells. In the present study, we examined the effect of staphyloccoccal enterotoxin A (SEA) on human T cells with NK cell markers, CD56 or CD57 (NK-type T cells). After stimulating peripheral blood mononuclear cells (PBMC) with SEA, PBMC produced a large amount of IFN- and acquired a potent antitumour cytotoxicity. The in vitro depletion of either CD56+ TCR NK cells, CD56+ T cells or 57+ T cells from PBMC significantly inhibited the IFN- production from PBMC. When purified NK-type T cells, NK cells and regular T cells were cultured with monocytes and SEA they all produced IFN-, while the IFN- amounts produced by both NK-type T cells were greater than those produced by NK cells. NK cells as well as CD56+ T cells showed cytotoxicity against NK-sensitive K562 cells, whereas both NK-type T cells showed a more potent cytotoxicity against NK-resistant Raji cells than did NK cells. The IFN- production from each population as well as from whole PBMC was greatly inhibited by anti-IL-12 antibody but not by anti-IL-18 antibody. The antitumour cytotoxicity of whole PBMC was also significantly inhibited by anti-IL-12 antibody while the SEA-induced proliferation of PBMC was not affected by anti-IL-12 antibody. Furthermore, SEA-activated NK-type T cells as well as NK cells showed cytotoxicities against vascular endothelial cells. Our findings suggest that human NK-type T cells are thus involved in bacterial superantigen-induced immune response.

Biomarkers↗

Doppler ultrasound monitoring for detection of microembolic signals in peripheral arteries.

OBJECTIVE: to use Doppler ultrasound to detect peripheral microemboluation. METHODS: standard Transcranial Doppler equipment was used to peripheral detect peripheral embolic high intensity transient signals (HITSs) in a pig model following injection of microparticles and atheroma, and in 23 patients who underwent open repair of an abdominal aortic aneurysm (AAA), six patients with blue toe syndrome and 10 age matched healthy subjects. RESULTS: the pig study showed increasing signal intensity with particle size. Particles of 100 (n=24), 200 (n=17), and 400 microm (n=31) elicited 14, 25, 33 dB signals, respectively (p<0.05). During AAA surgery, the intensity (median) of HITSs before clamping (n=226) and after declamping (n=1216) were 14, and 20dB, respectively (p<0.001). Quite a few HITSs were detected after surgery. In patients with blue toe syndrome, a total of 63 HITSs could be detected, and the frequency of HITSs (median: 5.72/30min) was significantly higher than that in patients with AAA before surgery (0.065/30min) (p<0.001). CONCLUSIONS: Doppler ultrasound technique may be a clinically useful test to guide the treatment of patients at risk of distal atheroembolic events.

Aged↗

Magnifying endoscopy, stereoscopic microscopy, and the microvascular architecture of superficial esophageal carcinoma.

BACKGROUND AND STUDY AIMS: In this study we clarify the microvascular architecture of superficial esophageal carcinoma as observed by ultra-high magnification endoscopy and stereoscopic microscopy with Microfil injection. PATIENTS AND METHODS: We observed two surgically resected specimens of superficial esophageal cancer under stereoscopic microscopy with Microfil injection. In addition, in the histological investigation, we measured the caliber of the vessels at the surface of the tumor. We carried out ultra-high magnification before treatment in 82 patients with superficial esophageal neoplasms. We classified the depth of tumor penetration of superficial esophageal carcinoma into four categories: m1 to m3 (mucosal cancer) and sm (submucosal cancer). RESULTS: By observing the normal esophageal mucosa under a stereoscopic microscope and an ultra-high magnification endoscope, we were able to visualize the intrapapillary capillary loops (IPCL). In cancer lesions, we observed characteristic changes in the superficial microvascular architecture according to the depth of tumor invasion. In m1 invasion, there was dilatation of the IPCL; in m2 invasion, there was dilatation and elongation of the IPCL; in m3, there was a mixed appearance of the IPCL and tumor vessels; and in sm invasion, complete replacement by tumor vessels. On the basis of the above criteria, ultra-high magnification endoscopic observation before treatment showed a rate of agreement between histological depth of invasion and magnified appearance of 60/72 cases (83.3 %) for which satisfactory pictures were obtained. The histological investigation showed the caliber of the IPCL of the m1 cancer lesions (12.9 +/- 3.9 microm) to be significantly greater than that of the normal esophageal mucosa (6.9 +/- 1.5 microm) (P < 0.0001). CONCLUSIONS: Observation of the microvascular architecture of superficial esophageal carcinoma is useful in the diagnosis of the depth of invasion.

Carcinoma↗

The proximal form of mural thrombus in aortoiliac occlusive disease using computed tomography.

BACKGROUND: It is important to know the nature of proximal thrombus in patients with aortoiliac occlusive disease (AIOD) when juxtarenal aortic clamping is scheduled. This study was aimed to evaluate the shape and nature of thrombi at several sites of the abdominal aorta in patients with AIOD using enhanced computed tomography (CT). Final judgment was made according to the operative findings. METHODS: Between the years 1999 and 2001, 22 patients, who underwent aortobifemoral bypass, were enrolled. The shape and nature of their thrombi were examined at 4 points (superior mesenteric, suprarenal, juxtarenal and infrarenal arteries at the level of the 2 cm before the renal artery) and 88 slices of CT were examined retrospectively. RESULTS: There was mural thrombus in 31 slices, which could be classified into 4 shapes (crescent-shaped: 10 cases; magatama: 2; wavy: 12; circular: 6). The wavy and circular shaped thrombi were found to be atheromatous. Nine cases (40.9%) on operative findings were atheroma (wavy: 4; circular shaped: 5). The crescent shape might correspond to fibrin thrombus. Atheromatous thrombus clamping near the renal artery was thought to cause microthromboembolism to surrounding organs. CONCLUSIONS: It is recommended that the more proximal aorta or splanchnic arteries should be temporarily clamped during proximal procedures in patients with wavy or circular shaped thrombi at the juxtarenal aorta to prevent kidney or bowel infarction.

Aged↗

Geometric approach to Lyapunov analysis in Hamiltonian dynamics.

As is widely recognized in Lyapunov analysis, linearized Hamilton's equations of motion have two marginal directions for which the Lyapunov exponents vanish. Those directions are the tangent one to a Hamiltonian flow and the gradient one of the Hamiltonian function. To separate out these two directions and to apply Lyapunov analysis effectively in directions for which Lyapunov exponents are not trivial, a geometric method is proposed for natural Hamiltonian systems, in particular. In this geometric method, Hamiltonian flows of a natural Hamiltonian system are regarded as geodesic flows on the cotangent bundle of a Riemannian manifold with a suitable metric. Stability/instability of the geodesic flows is then analyzed by linearized equations of motion that are related to the Jacobi equations on the Riemannian manifold. On some geometric settings on the cotangent bundle, it is shown that along a geodesic flow in question, there exist Lyapunov vectors such that two of them are in the two marginal directions and the others orthogonal to the marginal directions. It is also pointed out that Lyapunov vectors with such properties cannot be obtained in general by the usual method that uses linearized Hamilton's equations of motion. Furthermore, it is observed from numerical calculation for a model system that Lyapunov exponents calculated in both methods, geometric and usual, coincide with each other, independently of the choice of the methods.

Journal Article↗