Yukiko Okamoto

Factors affecting the volume of umbilical cord blood collections

Objective. Our purpose was to find factors that may help increase the number of the HSC ( CD34+) collected from umbilical cord blood for transplantation.

Effect of Chymase Inhibition on the Arteriovenous Fistula Stenosis in Dogs

It was hypothesized that chymase may participate in hemodialysis vascular access dysfunction, as chymase has been known to be an effective enzyme in the conversion of angiotensin I (Ang I) to Ang II and in the latent TGF-beta1 to the active form. An arteriovenous (AV) fistula was created between the brachial artery and vein in dogs. In the AV anastomosis, when the walls of the venous and arterial sides were compared, the eccentric neointimal formation was most evident in the venous wall. Compared with the venous side downstream of the AV anastomosis, a severe neointimal hyperplasia was found in the venous side upstream of the AV anastomosis (intima/media, 153 +/- 25%). The chymase- and TGF-beta-positive mast cells were markedly accumulated in the proliferous neointima and media. In association with the reduction of chymase expression, a marked decrease in Ang II-, AT(1) receptor-, and TGF-beta-positive areas was achieved by NK3201 (a chymase inhibitor) treatment, and the neointima formation (intima/media: region A, 53 +/- 9%, P < 0.001; region B, 54 +/- 14%, P < 0.001) was also significantly suppressed in this group. Although lisinopril treatment also provided some beneficial effects with regard to the prevention of neointimal formation, the degree was less than that seen with chymase inhibition. These findings indicate that mast cell-derived chymase plays an essential role in the pathogenesis of the AV fistula access failure and that chymase inhibition may be a therapeutic target for the treatment of hemodialysis vascular access dysfunction in clinic settings.

Attenuation of adhesion formation after cardiac surgery with a chymase inhibitor in a hamster model

OBJECTIVE Chymase is one of the inflammatory mediators and is released from mast cells, which are closely associated with adhesion formation. Chymase also activates transforming growth factor beta1, which promotes tissue fibrosis. However, the role of chymase in cardiac adhesion formation has not yet been elucidated. We have assessed whether a specific chymase inhibitor, Suc-Val-Pro-Phe(p) (OPh)(2), prevents postoperative cardiac adhesions in hamsters. METHODS In 66 hamsters the epicardium was abraded, and then either chymase inhibitor or placebo was injected into the left thoracic cavity, leaving the pericardium open. Cardiac chymase activity, the level of transforming growth factor beta1 in the pleural fluid, and the density of epicardial mast cells were measured 3 days postoperatively. The degree of adhesion formation was evaluated macroscopically and histologically 2 weeks postoperatively by using a grading score ranging from 0 (no adhesions) to 4 (severe adhesions). RESULTS The cardiac chymase activity and level of transforming growth factor beta1 were lower in the chymase inhibitor-treated group compared with in the placebo-treated group (45.8 +/- 18.7 vs 79.7 +/- 13.7 microU/mg protein [P <.025] and 15.6 +/- 6.5 vs 33.2 +/- 9.8 microg/mL [P <.01], respectively). The density of mast cells was higher in the placebo-treated group, and there was suppression to 60% of this value in the chymase inhibitor-treated group. The adhesion scores were lower in the chymase inhibitor-treated group compared with in the placebo-treated group (1.3 +/- 1.3 vs 3.0 +/- 1.1, P <.01). CONCLUSION Use of a chymase inhibitor suppresses not only cardiac chymase activity but also the level of transforming growth factor beta1, and this results in a reduction in postoperative cardiac adhesion.

Effect of Chymase-Dependent Transforming Growth Factor β on Peritoneal Adhesion Formation in a Rat Model

PurposeTo clarify the role of chymase produced from mast cells, which are closely related to adhesion formation, we investigated the preventive effect of a chymase inhibitor on adhesion formation in a rat model.MethodsA lesion was created in rats by uterus scraping, and a chymase inhibitor, Suc-Val-Pro-Phep(OPh)2 (10 µM), or a placebo was injected into the abdomen. The level of transforming growth factor β (TGF-β) in the peritoneal fluid was also measured.ResultsBy 2 weeks after the operation, the scores for adhesion formation in the chymase inhibitor-treated group were significantly lower than those in the placebo-treated group, at 1.64 ± 0.34 and 3.27 ± 0.19, respectively (P < 0.01). After scraping the uterus, the level of TGF-β in the peritoneal fluid was significantly higher in the placebo-treated group, whereas it was significantly suppressed by the chymase inhibitor.ConclusionsChymase may play an important role in adhesion formation aided by TGF-β.

Chymase inhibitor suppresses adhesion formation in a hamster experimental model

To clarify the role of chymase produced by mast cells in adhesion formation, we investigated the preventive effect of a specific chymase inhibitor, Suc-Val-Pro-Phe(p) (OPh)2, on adhesion formation in a hamster experimental model. Hamsters underwent resection of the right uterine body and then 10 microM Suc-Val-Pro-Phe(p) (OPh)2 or placebo was injected into the abdomen. Two weeks after the operation, the scores for adhesion formation in the chymase inhibitor-treated group were significantly lower than that in the placebo-treated group (placebo-treated group, 3.60+/-0.22; chymase inhibitor-treated group, 2.10+/-0.22; P<0.01). This specific chymase inhibitor, Suc-Val-Pro-Phe(p) (OPh)2, significantly suppressed the scores for adhesion formation in a hamster experimental model. Thus, chymase may play an important role in the adhesion formation.

Laparoscopic-Assisted Removal of a Large Urachal Cyst

A 48-year-old woman was seen because of an abdominal tumor. Laparoscopy was performed for diagnosis and treatment. A large cystic mass was hanging from the anterior abdominal wall and was removed with laparoscopic assistance. Histologic examination revealed a urachal cyst. (J Am Assoc Gynecol Laparosc 8(1):159-160, 2001)

Chymase inhibitors may prevent postoperative adhesion formation

OBJECTIVE To clarify the role of chymase produced from mast cells in adhesion formation, we measured chymase activity level and investigated the preventive effect of a chymase inhibitor, Suc-Val-Pro-Phe(p)(OPh)(2), on the postoperative adhesion formation. DESIGN Prospective randomized study using a surgical model for adhesion formation. SETTING Clean hamsters in an academic research environment. ANIMAL(S) Sixty-seven female Syrian hamsters. INTERVENTION(S) Hamsters were given a lesion, produced by uterus scraping, and the chymase inhibitor (10 microM) or placebo was injected into the abdomen. Chymase activities in uteri were measured 3 days after the operation, and the scores of adhesion formations were assessed at 2 weeks. MAIN OUTCOME MEASURE(S) Measurement of chymase activity and scoring of adhesion formation were performed. RESULT(S) A significant increase of chymase activity in the injured uterus reduced by treatment with the chymase inhibitor. The scores of adhesion formations in the chymase inhibitor-treated group were significantly decreased in comparison with those in the placebo-treated group. CONCLUSION(S) Chymase contained in mast cells plays an important role in adhesion formation, and a chymase inhibitor may be a useful drug for prevention of adhesion formation.

Laparoscopic-Assisted Surgery for Benign Ovarian Cyst in a Young Girl

A 7-year-old girl was admitted to our hospital because of sudden lower abdominal pain and vomiting. Emergency laparoscopy and cystectomy were performed, with a diagnosis of torsion of an ovarian cyst. All manipulations were possible through a 2-cm incision in the abdominal wall.

Attenuating Effects of Chymase Inhibitor on Pericardial Adhesion Following Cardiac Surgery

Abstract  Objective: Chymase, a serine protease, is released from mast cells, which is closely associated with adhesion formation. Chymase activates transforming growth factor‐β1 (TGF‐β1), which promotes tissue fibrosis. Recently we have found that chymase may play an important role in adhesion formation in hamsters. Accordingly, this study was designed to confirm that a chymase inhibitor prevents postoperative cardiac adhesions in large animals. Methods: In 14 dogs, the epicardium was abraded 200 times with gauze and the mid‐portion of the left anterior descending coronary artery (LAD) was exposed with No. 15 blade. Either chymase inhibitor (CI group, n = 7) or placebo (P group, n = 7) was sprayed into the pericardial cavity, then the pericardium was closed. Cardiac chymase activity, the level of TGF‐β1 in the pericardial fluid, the density of epicardial mast cells, the adhesion area between the heart and the pericardium, and the presence of adhesion between the mid‐LAD and the pericardium were evaluated 1 and 2 months after surgery. Five nonsurgical dogs were used as a control for cardiac chymase activity. Results: Cardiac chymase activity and TGF‐β1 level were lower in CI group than in P group (53.7 ± 35.0 vs. 93.4 ± 20.4 μU/mg protein, p = 0.01, 3.2 ± 0.9 vs. 4.3 ± 1.1 μg/mL, p = 0.06, respectively). In CI group, the density of mast cells (19 ± 5 vs. 32 ± 8 cells/cm, p < 0.01), the adhesion area (2.2 ± 0.8 vs. 7.5 ± 1.5 cm2, p < 0.01), and adhesions between the heart and the mid‐LAD (0% vs. 57%) were all reduced. Conclusion: Chymase inhibitor suppresses cardiac chymase activity and reduces the TGF‐β1 level, resulting in a reduction of cardiac adhesion in a large animal.

Chymase-derived angiotensin II and arrhythmias after myocardial infarction.

Mast cell-derived chymase seems to be important in the regulation of local angiotensin (A) II formation in cardiovascular tissues. In human heart, chymase accounts for 80% of A II formation. Therefore, the chymase-dependent A II pathway may play an important role in the pathogenesis of A II-related cardiovascular diseases. For example, cardiac chymase was activated earlier than ACE and this activation lasted longer than that of ACE after myocardial infarction (MI) in hamsters. Treatment with a specific chymase inhibitor treatment, but not an ACE inhibitor, improved post-MI survival as well as cardiac function and the extent of the beneficial effects was similar to that observed for an AT1-receptor antagonist treatment in this model. The survival benefit after MI seems to be related to an antiarrhythmic effect of the chymase inhibitor because chymase inhibition reduces the incidence of ventricular arrhythmias during periods of heart ischemia in a dog MI model. Thus, an antiarrhythmic effect of the chymase inhibitor may contribute to a reduction in mortality rate during the acute phase after MI.