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Biomedical subjects

T Ishimoto

Publications and source records attributed to T Ishimoto.

At least 19 recordsLinked to original sources

Abdominal aortic aneurysm repair with arterial branch reconstruction: utility of the temporary bypass technique.

Between June 1992 and May 1996, five patients underwent an abdominal aortic aneurysm (AAA) repair with concomitant arterial branch reconstruction. All of the patients were males ranging in age from 55 to 66 years (mean: 61.6 years). The operations were performed for a localized abdominal aortic dissection, a pseudoaneurysm after patch angioplasty of a supraceliac AAA, a pararenal AAA, a total AAA with retrograde descending thoracic aortic dissection, and a supraceliac AAA after an infrarenal AAA repair. All patients underwent bilateral renal artery (RA) reconstruction. Three patients also had a concomitant reconstruction of the superior mesenteric artery ad celiac axis. The renal arteries were preferentially reconstructed. Visceral circulation during aortic cross-clamping was maintained via a temporary bypass circuit. A temporary division of the left renal vein was necessary in two patients. Overall, the mean renal ischemia time was 17.2min (range: 10 to 32 min). There was one perioperative death due to sepsis from a graft infection. Another patient died 6 months postoperatively due to pyothorax. One patient required postoperative hemodialysis for 1 month. Based on the above findings, the temporary bypass technique is thus considered to be useful for maintaining physiologic organ perfusion during aortic clamping without the need to use any complicated devices.

Aged

A case of insufficient sleep syndrome.

All night polysomnographic evaluation (PSG) soon after admission and at the late period of admission revealed an atypically high sleep efficiency and a prolonged total sleep time. Sleep onset latency and distribution of REM and NREM sleep stages were like those of normal sleepers. On REM latency, while it was remarkably reduced (25.0 min) soon after admission and sleep onset REM period (SOREMP) was found, at the late period of admission it was prolonged and SOREMP was not found. Giving multiple sleep latency test with polysomnography, soon after admission subjective excessive daytime sleepiness had already improved and mean sleep latency (13.2 min) was within normal range. However, SOREMP appeared twice in five tests. We considered that the appearance at the early period of admission was the result of REM pressure growing.

Adult

In vitro and in vivo evidence for high frequency of I-Ab-reactive CD4+ T cells in HLA-DQ or HLA-DRA transgenic mice lacking endogenous MHC class I and/or class II expression.

Although T cells are educated to recognize foreign antigenic peptides in the context of self MHC molecules during their development in the thymus, peripheral T cells also recognize allo- and xeno-MHC molecules. The lower frequency of xeno-MHC-reactive T cells than that of allo-MHC-reactive T cells is often explained by the difference in the degree of homology between xeno- or allo-MHC and self MHC molecules, as well as by the species barrier of the molecules involved in immune recognition. To distinguish these two possibilities, we estimated the frequency of I-Ab-reactive CD4+ T cells selected by HLA-DQ or DR alpha E beta b molecules, using HLA-DQ6 and HLA-DRA transgenic C57BL/6 (B6) mice lacking endogenous MHC class I and/or class II molecules (DQ6A0/0 and DR alpha 30A0/0 beta 20/0). CD4+ lymph node T cells from DQ6A0/0 and DR alpha 30A0/0 beta 20/0 showed the strong proliferative response to I-Ab molecules. In addition, DQ6A0/0 and DR alpha 30A0/0 beta 20/0 rejected the skin graft from mice expressing I-Ab molecules irrespective of MHC class I expression, indicating that the CD4+ T cells recognizing I-Ab molecules are directly involved in this rejection. The estimated frequency of I-Ab-reactive CD4(+)CD8- thymocytes in DR alpha 30A0/0 beta 20/0 and DQ6A0/0 was comparable with that observed in the MHC class II-disparate strains. Our findings thus indicate that CD4+ T cells selected to mature on xeno-MHC class II molecules such as HLA-DQ6 or DR alpha E beta b, when these molecules are expressed in mice, recognize I-Ab molecules as allo-MHC class II, despite the less structural homology.

Animals

Echocardiographic characteristics and causal mechanism of physiologic mitral regurgitation in young normal subjects.

BACKGROUND: It has become evident that mitral regurgitation (MR) is not uncommon in healthy subjects, and Doppler color flow mapping is a technique that imparts important information relevant to its detection. HYPOTHESIS: Using transthoracic echocardiography, this study evaluated the mechanism of physiologic MR in young normal subjects using transthoracic echocardiography. METHODS: The study population consisted of 48 young normal subjects (mean 21 +/- 5 years) with MR (physiologic MR group), 40 age-matched young normal subjects (mean 20 +/- 5 years) without MR (control group), 45 patients (mean 41 +/- 15 years) with mitral valve prolapse with MR (MVP group), and 27 patients (mean 59 +/- 13 years) with ruptured chordae tendineae (rupture group). RESULTS: Men were predominant in the rupture group, whereas there were no significant gender differences in the other three groups. Left ventricular end-diastolic dimension and left atrial systolic dimension were slightly smaller in the physiologic MR group than in the control group, but were significantly smaller than those in the MVP and rupture groups. The ratio of the maximum anteroposterior diameter to the maximum transverse diameter on chest radiography and the ratio of the short- to long-axis diameter of the left ventricular cavity at end diastole, determined from two-dimensional short-axis echocardiogram, were significantly lower in the physiologic MR group than in the other three groups. Mitral regurgitation occurred more frequently at the posteromedial commissural site in the physiologic MR and MVP groups, whereas there was no preference for location in the rupture group. Early systolic MR was often observed in the physiologic MR group, whereas pansystolic MR was common in the MVP and rupture groups. CONCLUSION: As a causal mechanism for physiologic MR detected in young normal subjects, "flattening" of the thorax during growth may cause morphologic abnormalities of the left atrial and ventricular cavities, resulting in spatial imbalance of the mitral complex and resulting in malcoaptation of the valve.

Adult

Delayed manifestation of aortic stenosis after blunt abdominal trauma: report of a case.

Delayed manifestation of aortic stenosis caused by abdominal blunt trauma is rare. We report herein the case of a 67-year-old man who was taken to a nearby hospital after being crushed between a heavy truck and a wall. An emergency laparotomy was performed, revealing only a mesenteric tear which was repaired. He was discharged after an uneventful postoperative course; however, 1 month later he began to experience intermittent claudication, and presented to our hospital in December 1994, 1 year after the first operation. Angiography and enhanced computed tomography (CT) demonstrated infrarenal abdominal aortic dilatation with distal stenosis. Both the dilated and stenotic lesions were resected and bypass surgery ws performed. Pathologic examination demonstrated that the intima had been lacerated circumferentially and everted distally, causing the aortic stenosis. To our knowledge, this is the first case of the delayed manifestation of traumatic aortic stenosis to be documented in Japan. The etiology of this rare complication of blunt trauma is described in this report.

Abdominal Injuries

Positive and negative CD4+ thymocyte selection by a single MHC class II/peptide ligand affected by its expression level in the thymus.

The central event in thymic selection of T cells bearing alpha beta TCRs is their interaction with self-peptides bound to self-MHC molecules. With the use of transgenic mouse lines expressing a single peptide/MHC class II complex, we show that CD4+ T cells with the preferential usage of particular TCR V(alpha)s and V(beta)s were selected to mature on this complex in lines with the lower expression, whereas such CD4+ T cells were eliminated in the thymus in a line with the relatively high expression. When a low expressing line was crossed with a high expressing line, the frequency of CD4+ T cells selected by this complex markedly decreased. Thus, these results suggest that a single peptide/MHC class II complex, being affected by its cell surface density in the thymus, can serve as both positively and negatively selecting ligand in vivo.

Amino Acid Sequence

[Two cases of annulo-aortic ectasia with type A aortic dissection reconstructed by reimplantation of the aortic valve].

We performed aortic valve sparing operation in two cases of annulo-aortic ectasia combined with Type A aortic dissection. Marfan syndrome was found in one case and the dissection was acutely evolving in another case. The aortic valves were observed as normal configuration in both cases and then reimplanted within the synthetic grafts along with the David's procedure. No aortic regurgitation was found in the acute case but slight regurgitation was checked out in the Marfan case at the discharge. The aortic valve preserving operation for annulo-aortic ectasia was considered much effective in cases with aortic dissection in order to expect the thrombolization in the pseudo lumen.

Adult

Localised thrombus in the distal aortic arch: its aetiology analysed by three-dimensional mould model of the thoracic aorta.

Isolated thrombus of the thoracic aorta without aneurysmal change or dissection is a relatively rare event. A case presenting with aortic thrombus and successive distal embolism is reported herein and the aetiology of the thrombus of the distal aortic arch is analysed by a three dimensional aortic model. A 61-year-old man suffered acute ischaemia in his right leg on January 26, 1994. Enhanced computed tomography (CT) showed a localized thrombus in the distal aortic arch expanding towards the descending aorta, and partial infarction of the left kidney and the spleen. Angiography demonstrated abrupt occlusion of the right superficial femoral artery. Immediate anticoagulation with heparin and coumadin was administered, and the thrombus in the aorta disappeared following 1 month of this medical treatment, leaving the renal and splenic infarction unchanged. The unresolved occlusion of the superficial femoral artery and the popliteal artery was treated with a bypass from the right superficial femoral artery to the peroneal artery using a reversed saphenous vein graft. The mould model of the thoracic aorta was reconstructed from CT, and the thrombus was found to be at the most distal and medial site of the lesser curvature of the aortic arch. This specific location is referred mostly as the site for thrombus formation in the literature. The case is reported briefly and the risk of this specific region of the thoracic aorta for thrombus formation is discussed using this mold model.

Angiography

Importance of the phospholipase D-initiated sequential pathway for arachidonic acid release and prostaglandin D2 generation by rat peritoneal mast cells.

The association of prostaglandin D2 (PGD2) production as well as arachidonic acid release with the phospholipase D (PLD)-linked mechanism was studied in rat peritoneal mast cells. Stimulation of mast cells with cross-linking of the high-affinity Fc receptor for IgE caused increases in the release of arachidonic acid and PGD2, which are suppressed almost completely by ethanol or RHC 80267, a diacylglycerol lipase inhibitor. Ethanol did not influence inositol phosphate release in response to an antigen. An increase in diacylglycerol, that is inhibited by propranolol, was observed, with a peak within 1 min. Antigen stimulation induced little production of lysophosphatidylcholine, while ionomycin as a control markedly induced the production. However, the phospholipase A2 (PLA2) activity in the cytosol of antigen-stimulated cells increased to the level in ionomycin-stimulated cells. The addition of the ADP-ribosylation factor-containing fraction prepared from bovine brain, that is known to specifically activate PLD, to permeabilized mast cells in the presence of GTP gamma S, apparently increased arachidonic acid and PGD2 release, but not in the presence of ethanol. Furthermore, arachidonic acid release by an antigen was enhanced by melittin, that activates PLA2, but PGD2 production was not. These results suggest that antigen-stimulated PGD2 production as well as arachidonic acid release are strongly associated with the sequential PLD-linked pathway.

ADP-Ribosylation Factors

Requirement of calcium influx for hydrolytic action of membrane phospholipids by cytosolic phospholipase A2 rather than mitogen-activated protein kinase activation in Fc epsilon RI-stimulated rat peritoneal mast cells.

The mechanism by which cytosolic phospholipase A2 (cPLA2) is not responsible for eicosanoid production in rat peritoneal mast cells upon antigen stimulation [Ishimoto et al. (1996) J. Biochem. 120, 616-623] was investigated in the mast cells stimulated by cross-linking of the IgE receptor or with thapsigargin. Stimulation with thapsigargin, but not with antigen, resulted in apparent lysophosphatidylcholine (lysoPC) formation. Antigen stimulation significantly increased the activities of mitogen-activated protein (MAP) kinase and cPLA2. These activities were further potentiated by phorbol ester. The antigen elicited a rapid and transient increase in intracellular Ca2+ concentration, while thapsigargin produced a slow and sustained increase. Furthermore, a combination of antigen and thapsigargin rapidly increased and prolonged the intracellular Ca2+ concentration. Under these conditions, lysoPC was apparently generated, whereas it was not in response to antigen alone. These results suggest that a prolonged increase in the intracellular Ca2+ concentration is required for cPLA2 to associate with membranes, thus leading to hydrolysis of membrane phospholipids by the enzyme.

Animals

Effect of berbamine on cytosolic phospholipase A2 activation in rabbit platelets.

The effect of berbamine, a biscoclaurine alkaloid, on cytosolic phospholipase A2 activation in rabbit platelets was investigated. Berbamine inhibited arachidonic acid liberation induced by thrombin but not that by ionomycin. The alkaloid did not affect thrombin-stimulated Ca2+ mobilization. Ca(2+)-dependent translocation of cytosolic phospholipase A2 to membranes, or the activity of partially purified cytosolic phospholipase A2. Furthermore, berbamine had no effect on the thrombin-elicited increase in cytosolic phospholipase A2 activity. However, berbamine suppressed arachidonic acid liberation in platelets stimulated with GTP-binding protein activators. Although incubation of platelet membranes with a GTP analogue decreased the islet-activating protein-catalyzed ADP-ribosylation of an approximately 40 kDa protein in the membranes, pretreatment of the membranes with berbamine did not influence the decrease in ADP-ribosylation. These results suggest that berbamine may impair GTP-binding protein-mediated activation of cytosolic phospholipase A2, probably without influencing the enzyme translocation to membranes or the increase in the enzyme activity, and thus may cause the suppression of thrombin-induced arachidonic acid liberation.

Alkaloids

Contribution of phospholipases A2 and D to arachidonic acid liberation and prostaglandin D2 formation with increase in intracellular Ca2+ concentration in rat peritoneal mast cells.

The contribution of phospholipases A2 (PLA2) and D (PLD) activation to arachidonic acid liberation and prostaglandin D2 (PGD2) formation was studied in stimulated rat peritoneal mast cells. Stimulation of the cells with ionomycin induced time-dependent and Ca(2+)-concentration-dependent increase in arachidonic acid liberation and PGD2 formation, and the Ca(2+)-dependent increase was especially remarkable at extracellular Ca2+ concentration higher than 200 microM. Staurosporine did not induce any effect on the arachidonic acid liberation, indicating that protein kinase C is not involved in the liberation. Addition of ethanol to the cells decreased the ionomycin-stimulated arachidonic acid liberation to 40% of the control, while it decreased the PGD2 formation almost completely, with the increase in phosphatidylethanol formation. Propranolol, a phosphatidate phosphohydrolase inhibitor, caused similar effects. p-Bromophenacyl bromide, a PLA2 inhibitor, inhibited partially the arachidonic acid liberation. The inhibition of the liberation by combination of p-bromophenacyl bromide and ethanol was additive and reached approximately 90%. Under the conditions used p-bromophenacyl bromide did not influence significantly the PLD activity assessed by the phosphatidylethanol formation. Histamine release was decreased by ethanol treatment to 35% of the control. These results suggest that more than half of the total arachidonic acid liberation is mediated by the sequential pathway of PLD/phosphatidate phosphohydrolase/diacylglycerol lipase and more than half of histamine release is also dependent on PLD activation, while the PGD2 formation is fully mediated by the pathway. PLA2 also contributes to arachidonic acid liberation but to a lower extent.

Acetophenones

Enhancement of phospholipase A2 activation by phosphatidic acid endogenously formed through phospholipase D action in rat peritoneal mast cell.

Contribution of phosphatidic acid (PA) generated by activated phospholipase (PL) D to PLA2 activation was studied in rat peritoneal mast cells. Exogenous didecanoyl PA induced arachidonate liberation in the permeabilized cells which was inhibited by p-bromophenacyl bromide. Upon exposure of the cells to ethanol in a high enough concentration to prevent PA formation, A23187-induced arachidonate liberation was suppressed by 50% and the rest was completely inhibited by p-bromophenacyl bromide. In contrast, propranolol, which enhanced PA accumulation, significantly increased the arachidonate liberation. These results suggest that A23187-induced PLA2 activation may be potentiated, at least in part, by PA generated through PLD action.

Animals

Selective infiltration of B cells committed to the production of monoreactive rheumatoid factor in synovial tissue of patients with rheumatoid arthritis.

B cells were directly cloned using EBV transformation fron the synovial tissue of patients with rheumatoid arthritis (RA), the objective being to investigate the B cell repertoire at the site of inflammation. The frequency of clones producing antibodies with rheumatoid factor (RF) activity was approximately 10% in those from the RA synovial tissue. Similar percentages of B cell clones from the peripheral blood of both RA patients and healthy controls also produced RF. However, almost all of these clones from the peripheral blood produced RF reactive not only with rabbit IgG or human IgG Fc but also with several other antigens (polyreactive). Only one of 654 clones (0.15%) from the RA peripheral blood produced RF specific to rabbit IgG or human IgG Fc (monoreactive). On the other hand, the frequency of clones producing monoreactive RF was approximately 30 times higher in RA synovial tissue. Furthermore, these B cells were activated in vivo to produce antibodies, since monoreactive RF was spontaneously produced from synovial tissue cells without the addition of B cell stimulators. No clones producing monoreactive RF were obtained from the synovial tissue of patients with osteoarthritis. These results suggest selective infiltration and/or proliferation of B cells committed to the production of monoreactive RF in RA synovial tissue.

Antibody Specificity

Role of superoxide dismutase in resistance of Porphyromonas gingivalis to killing by polymorphonuclear leukocytes.

Porphyromonas gingivalis in which the synthesis of superoxide dismutase (SOD) was induced by nitrate or by aeration was rendered resistant to killing by polymorphonuclear leukocytes. SOD purified from either anaerobically maintained or aerated cells also inhibited bacterial killing when added exogenously, and no difference between the effects of the two SODs was observed. These results suggest that SOD may form part of a defense mechanism that helps protect P. gingivalis against killing by polymorphonuclear leukocytes.

Blood Bactericidal Activity

Induction of signet ring cell carcinomas in X-irradiated hypocatalasemic mice (C3H/Cbs).

The stomach region of hypocatalasemic mice of both sexes was X-irradiated once with a dose of 20 Gy. Thirteen months after the irradiation, 3 out of 13 (20%) males and 2 out of 9 (15%) females were observed to have developed signet ring cell carcinomas in the glandular stomach. This finding was statistically significant (P less than 0.01 in males and P less than 0.05 in females) compared to a total absence of similar tumors in the non-irradiated controls. Local invasion of malignant tumors into muscle and subserosal layers was observed, but no metastatic tumors were found in distant organs.

Acatalasia