Nonmuscle myosin heavy chain and metalloproteinase-2 expression in concordant pulmonary xenografts.
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Biomedical subjects
Publications and source records attributed to M Kawauchi.
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BACKGROUND: The mechanisms of intimal thickening in cardiac allograft vasculopathy (CAV) remain controversial after heart transplantation. Matrix metalloproteinase-2 (MMP-2) plays a crucial role in degrading extracellular matrix (ECM) during neointimal formation. Recently, it has been revealed that MMP-2 is activated by membrane-type 1 matrix metalloproteinase (MT1-MMP). This process involves tissue inhibitor of MMP-2 (TIMP-2), forming an MT1-MMP/TIMP-2/pro-MMP-2 complex. In this study, we hypothesize that these components contribute to the pathogenesis of CAV. METHODS: Heterotopic cardiac allografting was performed in randomly paired Japanese monkeys with an immunosuppressive regimen of intravenous administration of antihuman CD18 monoclonal antibody. The donor hearts were harvested at Days 22, 28, 40, 41, and 95 posttransplantation. We examined expression of MMP-2, MT1-MMP, and TIMP-2 of graft vessels using immunohistochemistry and protein level by western blot analysis. RESULTS: Pathologically, various degrees of neointimal formation were observed. In the allografts harvested at Days 22, 28, 40, and 41, MT1-MMP was expressed in the endothelial cells and smooth muscle cells (SMCs) in media of some arteries without histological change, accompanied by expression of MMP-2 and TIMP-2. In the severely thickened neointima of the allograft harvested at Day 95, MMP-2 and faint MT1-MMP were expressed in SMCs of severely thickened neointima and media; TIMP-2 expression was seen only in noncollagenous tissue of severely thickened neointima. MMP-2 protein was more intensely expressed in the allograft harvested at Day 95 than in the allograft harvest at Day 41, while TIMP-2 protein level was almost same in the 2 samples. CONCLUSION: We observed the simultaneous expression of MMP-2, MT1-MMP, and TIMP-2. Thus, ECM degradation triggered by MT1-MMP/TIMP-2/pro-MMP-2 complex could be a novel mechanism of CAV.
Hydrocephalus occasionally causes West syndrome, but the mechanism is unknown. We experienced a case with West syndrome and congenital hydrocephaly, in which the EEG findings improved after the resolution of shunt complications. The course of this case implied the pathogenesis of West syndrome associated with congenital hydrocephaly, as well as the origin of the seizures and that of the EEG findings in West syndrome. A 7-month-old girl had congenital hydrocephaly. A prenatal diagnosis was made by ultrasonography, and ventricle-peritoneal shunting was performed 7 days after birth. During the following 7 months several shunt replacements were done because of recurrent shunt complications. Her first series of infantile spasms began at the age of 6 months, and treatment was started under the diagnosis of West syndrome. One month later, her seizures were controlled by pyridoxal phosphate, while the EEG still showed hypsarrythmia. Her shunt was then removed again, because of bacterial meningitis due to shunt infection. The recovery from shunt complication resulted in marked improvement of the hypsarrhythmia. Our experience and previous literature suggest the involvement of cerebral cortex in the occurrence of West syndrome associated with congenital hydrocephaly.
The purpose of this article is to present a very rare case of Stanford type A acute aortic dissection featuring a swinging motion of the cylinder-shaped intimal flap through the aortic valve. The patient was a 62-year-old male suffering from severe cardiogenic shock. A transthoracic echocardiogram revealed aortic dissection and severe aortic regurgitation. A transesophageal echocardiogram demonstrated that the aortic dissection in the ascending aorta was circumferential and the proximal portion of the intimal flap was swinging through the aortic valve, ie., falling into the left ventricle during the diastolic phase and being ejected back into the ascending aorta during the systolic phase. An emergency graft replacement of the ascending aorta was performed. During ventricular fibrillation under total cardiopulmonary bypass, we performed cardiac massage to prevent myocardial ischemia, because blood flow from a heart lung machine inverted the intimal flap, which might have disturbed the coronary circulation. The patient's postoperative course was uneventful, and his postoperative echocardiogram revealed only a trace of regurgitant flow through the aortic valve. Back-and-forth movement of the cylinder-shaped intima requires coexistence of the following three conditions: severe aortic regurgitation, circumferential dissection, and complete transection of the intimal flap. We conclude that this movement of the intimal flap should be regarded as one of the most serious complications leading rapidly to cardiogenic shock. From a surgical point of view, it is most important to prevent myocardial ischemia during cardiopulmonary bypass especially in cases in which ventricular fibrillation has occurred. We describe the ways to prevent myocardial ischemia in this rare situation.
From 1989 to 1998, 721 patients with head injury were admitted to our department and 22 (3.1%) of them developed posttraumatic hydrocephalus. These patients included 16 males and 6 females, ranging in age from 17 to 86 years (mean age, 66 yrs) with peak incidence in the eighth decade. CT scan on admission immediately after head injury showed subarachnoid hemorrhage (SAH) in 18 cases. The other 4 cases without SAH had once suffered head injuries severe enough to give rise to consciousness disturbance. The typical clinical symptoms of hydrocephalus were observed in only 5 (23%) patients, and in the other 17 cases prolonged or deteriorated of consciousness disturbance were the main symptoms. Hydrocephalus was diagnosed between 1 and 3 months in 15 cases and in 7 cases after 4 months. Clinical improvement has been seen in 17 (77%) cases and marked recovery of consciousness was achieved in 12 cases after V-P shunt, but 5 cases with severe disturbance of consciousness revealed no improvement of clinical signs even after decrease of ventricular size. These results indicate that elderly patients with traumatic SAH should be followed up for at least 4 to 5 months, paying attention to development of hydrocephalus, and V-P shunt would be effective to improve consciousness disturbance in most of the cases.
A patient who was admitted to our hospital to undergo surgery for a dissecting thoracic aneurysm suffered preoperatively from severe acute pancreatitis with pancreatic pseudocysts. Computerized tomography (CT) demonstrated the presence of new fluid collection around the cyst with the absence of pancreatic necrosis. He was given a somatostatin analog (sandostatin), which was effective in decreasing the abdominal symptoms, leukocyte counts, and the serum C-reactive/protein level. A CT scan revealed that the pancreatic pseudocyst and peripancreatic fluid collection had disappeared. Although somatostatin has been reported to be ineffective for acute pancreatitis with necrosis, pancreatitis without necrosis may regress after treatment with sandostatin. This is probably due to its suppressive effect on the exocrine function, thus resulting in a decrease of pancreatic juice infiltration.
BACKGROUND: In the surgical treatment of acute aortic dissection, intractable hemorrhage often occurs. We performed an animal study to test the hypothesis that a new sealant, AdvaSeal (Ethicon Inc, Johnson & Johnson Medical KK, Somerville, NJ), can close the false channel of aortic dissection. METHODS: Acute descending aortic dissection was created surgically in 12 mongrel dogs. In 7 of these (treated group), AdvaSeal was applied to the false cavity for reinforcing and fusing the dissected layers and also to the suture line. The other 5 dogs (control) were left untreated. Specimens were harvested 2 weeks after surgery. RESULTS: The sealant could be used in wet conditions. In the treated group, hemostasis was easily achieved during surgery. All false cavities were perfectly thrombosed, causing no deleterious effects related to the sealant. In the control group, all false lumina remained patent. CONCLUSIONS: The advantage of AdvaSeal was its effectiveness on wet tissue and its adhesiveness, allowing good hemostasis and closure of the false lumen. The sealant can be an easy and efficacious sealant in treatment for acute aortic dissection.
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BACKGROUND: Hyperbilirubinemia is not uncommon and is sometimes fatal after valvular surgery. One important cause of it is a poor functional liver reserve, however, conventional tests reflect hepatic blood flow and do not offer precise evaluation of the pure functional liver reserve. Antipyrine has particular pharmacological properties, and its plasma clearance represents quantitatively the functional capacity of the liver. In this study, we measured antipyrine plasma clearance in cardiac surgical patients and evaluated the feasibility of using this parameter as a predictor of the risk of postoperative hyperbilirubinemia. METHODS: The plasma clearance of antipyrine was measured preoperatively in 40 cardiac patients undergoing mitral and/or tricuspid valvular surgery and its relations with hemodynamics or postoperative course were studied. RESULTS: Antipyrine clearance in preoperative patients was 0.365+/-0.175 (mean +/- SD) ml/min/kg, lower than the normal range (0.405+/-0.04 ml/min/kg), and showed no correlation with cardiac index, while the plasma disappearance rate of indocyanine green depended on the cardiac index. The maximum postoperative total bilirubin level showed significant correlation with antipyrine clearance (r=-0.699); this correlation coefficient was greater than that with indocyanine green (-0.477). The correlation was more prominent in patients with cardiac dysfunction. Furthermore, antipyrine clearance showed significant predictability of the duration of ICU stay. CONCLUSIONS: Antipyrine clearance provides a precise estimate of functional liver reserve which is independent of hemodynamics and predicts the risk of postoperative hyperbilirubinemia in preoperative cardiac patients.
To analyze the effect of lecithinized superoxide dismutase (SOD) on superoxide accumulation after traumatic brain injury (TBI) in rats, we studied the SOD activity by NBT-reducing method and the expression of Cu,Zn-SOD mRNA by Northern blot analysis. As determined by the specific gravity method, the administration of lecithinized SOD decreased brain edema in the periphery of the lesion at 6 hr after contusion. SOD activity, without lecithinized SOD administration, increased at the peripheral portion at 30 min after contusion, but decreased to normal level at 6 hr after TBI. By administration of lecithinized SOD, the increase of SOD activity was preserved until 6 hr after TBI. The expression of Cu,Zn-SOD mRNA increased in the core lesion, peripheral portion, and contralateral hemisphere until 6 hr after TBI, then was suppressed in all three areas by lecithinized SOD. These results support the hypothesis that superoxide anions may play an important role in the development of brain edema after TBI, and that leciyhinized SOD appears to prevent brain edema through a protective effect against superoxide anions.
Endovascular covered stents were successfully applied to temporarily halt hemoptysis and postpone surgical intervention in a 69-year-old man with a ruptured anastomotic false aneurysm of the distal aortic arch. Surgical graft implantation was performed successfully by the elephant trunk technique 14 days after the endovascular stent-grafting, at which time aspiration pneumonia had subsided.
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