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Biomedical subjects

M Watari

Publications and source records attributed to M Watari.

At least 19 recordsLinked to original sources
PubMed2001

The extra domain A of fibronectin activates Toll-like receptor 4.

Cellular fibronectin, which contains an alternatively spliced exon encoding type III repeat extra domain A (EDA), is produced in response to tissue injury. Fragments of fibronectin have been implicated in physiological and pathological processes, especially tissue remodeling associated with inflammation. Because EDA-containing fibronectin fragments produce cellular responses similar to those provoked by bacterial lipopolysaccharide (LPS), we examined the ability of recombinant EDA to activate Toll-like receptor 4 (TLR4), the signaling receptor stimulated by LPS. We found that recombinant EDA, but not other recombinant fibronectin domains, activates human TLR4 expressed in a cell type (HEK 293 cells) that normally lacks this Toll-like receptor. EDA stimulation of TLR4 was dependent upon co-expression of MD-2, a TLR4 accessory protein. Unlike LPS, the activity of EDA was heat-sensitive and persisted in the presence of the LPS-binding antibiotic polymyxin B and a potent LPS antagonist, E5564, which completely suppressed LPS activation of TLR4. These observations provided a mechanism by which EDA-containing fibronectin fragments promote expression of genes involved in the inflammatory response.

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PubMed2001

Kinetics of pro-inflammatory cytokines release in cardiac surgery with cardiopulmonary bypass.

OBJECTIVE: Cytokine induction can occur routinely in cardiac surgery with cardiopulmonary bypass. We have studied the relationships between the kinetics of pro-inflammatory cytokine release and the postoperative organ function. METHODS: Ten adult patients (6 men and 4 women) undergoing elective cardiac surgery with cardiopulmonary bypass, at Hiroshima University Hospital were studied. Patients with acute infection, insulin-dependent diabetes, acute or chronic respiratory failure, renal or hepatic failure, acute cardiogenic shock, and emergency patients were not included. The age of the patient ranged from 44 to 78 years (mean 69 +/- 2.0 years). The type of surgical intervention performed was coronary artery bypass grafting in four patients, mitral valve plasty or replacement with modified maze procedure in another five patients, and both procedures in the other one patient. Plasma cytokine levels until 48 hours after aortic declamping were measured in blood samples. The Respiratory Index and the serum levels of choline esterase and creatinine were also measured. The plasma levels of the pro-inflammatory cytokines (interleukin-6 and interleukin-8) were measured. RESULTS: The highest interleukin-6 levels were significantly correlated with hepatic dysfunction (r = -0.80, p = 0.006) and with renal dysfunction (r = 0.78, p = 0.009). The highest interleukin-8 levels were significantly correlated with respiratory dysfunction (r = 0.86, p = 0.001). CONCLUSION: The highest proinflammatory cytokines levels at 1 hour after aortic declamping were related to damage to postoperative organ functions, involving the lung, kidney and liver.

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PubMed2001

Clinical implication of orbital ultrasound monitoring during selective cerebral perfusion.

BACKGROUND: We evaluated clinical relevance of orbital ultrasound (OUS) monitoring to neurological events in aortic surgery associated with selective cerebral perfusion (SCP). METHODS: In 24 consecutive cases, blood flow was monitored at central retinal artery (CRA) and retrobulbar vessels. The threshold perfusion pressure for detecting CRA flow in the color Doppler mode (BPt) was determined in individual eyes. RESULTS: The BPt ranged from 25 to 71 mm Hg. Events (infarction, anisocoria, delirium) occurred in 8 cases. Infarction occurred in all 3 cases when retrobulbar flow was severely impaired for 40 minutes or longer, while none of the remaining 21 cases had infarction (p = 0.0005). Among the latter cases, perfusion pressure was below BPt for longer than 100 minutes in all 5 cases with events, and in 5 of 16 cases without events (p = 0.0124). No significant difference was found in age, duration of cardiopulmonary bypass, SCP, and circulatory arrest, and duration of blood pressure below 50 mm Hg. CONCLUSIONS: Sustained hypoperfusion detected with OUS monitoring is related to an occurrence of neurological events.

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PubMed2001

Clinical analysis of results of a simple left atrial procedure for chronic atrial fibrillation.

BACKGROUND: We have performed a simple left atrial procedure for eliminating chronic atrial fibrillation (AF) associated with mitral valve disease. This article analyzes the midterm results of this procedure. METHODS: Thirty-two patients were enrolled in this study concomitant with mitral valve operations. Patients were divided into two groups (AF- and AF+). We examined the efficacy of this operation and atrial function for more than 12 months of follow-up. RESULTS: In a total of 98.5 patient years of follow-up, AF was absent 3 years after operation in 74%. Of preoperative and intraoperative variables, only long duration o

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PubMed2001

Cardiac papillary fibroelastoma on the pulmonary valve: a rare cardiac tumor. okaken@mcai.med.hiroshima-u.ac.jp.

We report the case of a patient with a rare papillary fibroelastoma on the pulmonary valve visualized before surgical intervention. The tumor was an encapsulated, rounded mass. The gelatinous membrane on the surface tore easily, and multiple fronds appeared. This case emphasizes that when there is an encapsulated mass attached to a valve, the initial excision of valve tissue should be as minimal as possible. To avoid unnecessary injury to the valve, it is simple and practical to confirm that the tumor has the appearance of a sea anemone, thus identifying it as a papillary fibroblastoma, a benign tumor.

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PubMed2001

Efficacy of pulmonary vein isolation for the elimination of chronic atrial fibrillation in cardiac valvular surgery.

BACKGROUND: Haissaguerre and colleagues emphasize the importance of the pulmonary veins as a source of ectopic foci for initiating paroxysmal atrial fibrillation (AF). We hypothesized that ectopic foci from the pulmonary veins could also act as drivers for maintaining chronic AF, and that surgical ablation of the pulmonary vein orifices could terminate chronic AF. METHODS: Using a computerized 48-channel mapping system, we performed intraoperative atrial mapping in 12 patients with chronic AF associated with mitral valve disease. Patient age ranged from 24 to 82 years (mean, 60.4 years). AF duration ranged from 3 to 240 months (mean, 92+/-84 months). Simple surgical isolation of the pulmonary vein orifices was performed during the mitral valve operation. RESULTS: Regular and repetitive activation was found in the left atria of 9 out of 12 patients, and irregular and chaotic activation was found in both atria of 3 out of 12 patients. Chronic AF in the 9 patients (75%) with regular and repetitive activation of their left atria was successfully treated by a simple surgical isolation of the pulmonary vein orifices. The other 3 patients did not recover sinus rhythm after this procedure. In 1 case of recurrent AF, the patient recovered sinus rhythm during the follow-up period (AF-free rate, 83%). CONCLUSIONS: Surgical ablation of the pulmonary vein orifices was effective in the treatment of chronic AF associated with mitral valve disease. Intraoperative mapping may be useful in predicting the efficacy of a single pulmonary vein orifice isolation procedure.

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PubMed2001

Endovascular stent-grafting via the aortic arch for distal aortic arch aneurysm: an alternative to endovascular stent-grafting.

OBJECTIVE: We have experienced transaortic stent-grafting for treating distal arch aneurysm or type B dissection. This paper is to mainly report the surgical aspect of these procedures. METHODS: Fifteen patients underwent this surgery, including 12 men and three women ranging from 47 to 83 years. Twelve had aneurysms and three aortic dissection. Concomitant surgery was necessary in seven patients (coronary artery bypass grafting in five, tricuspid annuloplasty in one, and replacement of ascending aorta and/or total arch replacement in three cases). A stent graft (Gianturco Z-stent and Intervascular prosthesis) was loaded in a 30-F sheath catheter. Under circulatory arrest, selective cerebral perfusion was established, and the sheath catheter was inserted through aortotomy into descending aorta and the stent graft was deployed at an appropriate level. The proximal end of graft was sutured to the aorta just distal to the left subclavian artery with inclusion method at the posterior wall. Concomitant surgery was done during cooling or rewarming period. TEE was utilized to visualize every endovascular manipulation to avoid unintended intimal injury or misplacement of graft and to assess the surgical results in the operative theater. RESULTS: Aneurysm was successfully excluded except in one patient who had a proximal endoleak and distal endoleak due to underestimation of aortic diameter. There was one operative mortality caused by cerebral infarction, possibly due to debris from femoral arterial cannulation. In the remaining patients, there was no enlargement of residual aneurysm. The excluded aneurysmal sac gradually regressed and disappeared within 2 years in five patients and the thrombosed false lumen completely shrunk within 1 year in two patients. One patient had paraplegia, possibly because the graft was intentionally advanced deeply to cover the thick and fragile atheromatous layer in order to avoid destruction of the atheroma by an expanded graft. CONCLUSIONS: Endovascular stent graft via the aortic arch is an acceptable treatment for distal arch aneurysms close to or involving left subclavian artery or type B dissections, especially for those cases requiring other cardiac procedures. It can lead to regression and disappearance of aneurysm or dissection in the mid-term follow-up.

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PubMed2001

Pulmonary vein orifice isolation for eliminating paroxysmal atrial fibrillation after ICD implantation.

We treated a patient with dilated cardiomyopathy (DCM) and sustained ventricular tachycardia by an implantable cardioverter defibrillator (ICD). He then suffered from inappropriate ICD shocks triggered by paroxysmal atrial fibrillation (AF). We successfully performed pulmonary vein orifice isolation to eliminate paroxysmal AF. The pulmonary vein orifice isolation was a simple and useful procedure for eliminating paroxysmal AF in patient with decreased left ventricular (LV) function after ICD implantation.

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PubMed2001

[Serum cytokine levels response to cardiac surgery with cardiopulmonary bypass].

The response of tumor necrosis factor alpha (TNF alpha), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), interleukin-1 receptor antagonist (IL-1ra), macrophage colony stimulating factor (MCSF), white blood cell (WBC), platelet (Plt), lactic acid (LAC) to cardiopulmnary bypass (CPB) were studied until 48 hours after aortic declamping in 11 patients who underwent elective CABG (n = 4), mitral valve plasty or replacement with modified maze procedure (n = 5), and both procedures (n = 2). The highest levels of the cytokines IL-6, IL-8, IL-10, and IL-1ra were observed after the removal of the cross clamp. These cytokines just after the aortic declamping are likely to be occurred not only by an interaction of the blood components with the artificial surfaces, but also by ischemia-reperfusion injury upon discontinuation of the aortic clamping. MCSF increased gradually in the late post-CPB phase and reached a peak at 48 hr after aortic declamping. MCSF may play an important role in regulating hematopoiesis on the postoperative days 1 and 2 in patients. In conclusion, the therapy based on the kinetics of these cytokines would be useful for patients undergoing CPB.

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PubMed2000

Determinants of NPC1 expression and action: key promoter regions, posttranscriptional control, and the importance of a "cysteine-rich" loop.

Mutations in the NPC1 gene cause Niemann-Pick type C disease, which is characterized by the accumulation of free cholesterol and other lipids in lysosomes. The NPC1 glycoprotein is located in a late endosomal compartment that transiently interacts with lysosomes. To identify factors regulating NPC1 expression and action, we analyzed the function of the human NPC1 promoter in human-derived ovarian, hepatic, and neuronal cells. A fragment containing the first 208 base pairs upstream from the major transcription initiation site was sufficient to drive near maximal NPC1 promoter activity. Deletion analysis revealed that sequences between base pairs -111 and -37 play an important role in controlling NPC1 transcription. Treatment of proliferating granulosa cells with 30 microM progesterone, which induces a reversible phenocopy of the cholesterol trafficking defect of Niemann-Pick type C disease, increased NPC1 mRNA levels threefold. The protein synthesis inhibitor, cycloheximide, also increased NPC1 mRNA levels, augmenting the progesterone-induced increase in NPC1 mRNA abundance. Progesterone treatment was shown to increase the mRNA half-life, but did not affect NPC1 promoter activity. Cysteine residues in a "cysteine-rich" loop predicted to reside in the intralumenal compartment of vesicles containing NPC1 were mutated, resulting in proteins that were incapable of correcting the cholesterol trafficking defect in CT60 cells, a Chinese hamster cell line in which the endogenous NPC1 gene is inactivated. Converting isoleucine 1061, also predicted to lie within the cysteine-rich loop, to a threonine residue inactivated the protein as well. The I1061T mutation is one of the most common mutations in Niemann-Pick type C disease. All of the cysteine-rich loop mutants were localized to cholesterol-engorged lysosomes in a pattern mimicking the distribution of NPC1 in progesterone-treated cells. A recombinant protein representing the cysteine-rich loop was shown to bind to a zinc-NTA agarose column. We conclude: (1) that cis elements residing in the first 111 base pairs upstream from the transcription start site are critical for transcription of the NPC1 gene; (2) that NPC1 expression is subject to posttranscriptional regulation in response to treatments that disrupt NPC1 function; and (3) that an intralumenal cysteine-rich loop with zinc-binding activity is critical to NPC1's ability to unload lysosomal cargo.

Animals↗
PubMed2000

Evaluation of motor- and sensory-evoked potentials for spinal cord monitoring during thoracoabdominal aortic aneurysm surgery.

OBJECTIVE: To assess the utility of spinal cord monitorings for prediction of spinal cord ischemia, we investigated the role of both motor evoked potentials and sensory evoked potentials during thoracoabdominal aortic aneurysm surgeries. METHODS: We monitored two kinds of sensory evoked potentials; descending evoked spinal cord potentials from the lumbar enlargement after cervical spinal cord stimulation and segmental evoked spinal cord potentials at the lumbar enlargement elicited by peroneal nerve stimulation, and motor evoked potentials from the lumbar enlargement elicited by direct subcranial stimulation in 9 thoracoabdomonal aortic aneurysm surgeries. RESULTS: Postoperative paraplegia occurred in one case in which the patients died during the perioperative period. One case showed transient paraparesis, but recovered following rehabilitatation. These cases showed a decrease in the amplitude of descending evoked spinal cord potentials and motor evoked potentials. CONCLUSION: The recovery of the amplitude of the motor evoked potentials and the descending evoked spinal cord potentials after declamping correlated with the neurologic outcome.

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PubMed2000

Endovascular stent-grafting through the aortic arch: an alternative approach for distal arch aortic aneurysm.

BACKGROUND: Endovascular stent-grafting is an innovative procedure; we have developed a novel approach to treat distal arch aortic aneurysm through a small incision in the aortic arch. METHODS: Eight patients with thoracic aortic aneurysms were treated with an endovascular stent-graft that was introduced into the thoracic aorta through a small incision in the aortic arch. Of these patients, 7 had distal arch aortic aneurysms, and 1 had chronic aortic dissection of Stanford type B. Four of these patients had received concomitant coronary artery bypass grafting, and 1 patient had undergone tricuspid valvular annuloplasty. The stent-graft was introduced into the distal arch aorta and descending aorta through a small incision in the aortic arch, under selective cerebral perfusion and hypothermic circulatory arrest. RESULTS: The selective cerebral perfusion time ranged from 52 to 86 minutes (mean, 68 minutes) and the operating time from 289 to 422 minutes (mean, 318 minutes). There was no endoluminal leakage into the aneurysm. Seven patients survived and were discharged, but 1 patient suffered a cerebral infarction and died during the follow-up period. CONCLUSIONS: Placing an endovascular stent-graft through the aortic arch is an acceptable alternative treatment for distal arch aortic aneurysms.

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