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Biomedical subjects

Yoshimasa Sakamoto

Publications and source records attributed to Yoshimasa Sakamoto.

16 recordsLinked to original sources

Midterm results of mitral valve repair with the Carpentier-Edwards rigid ring.

OBJECTIVE: Prosthetic annuloplasty rings play an important role in mitral valve repair. This clinical study was undertaken to evaluate the midterm results obtained with the Carpentier-Edwards rigid ring. METHODS: Between October 1991 and March 2005, 112 patients (mean age 53.0 years) underwent mitral valve repair with a Carpentier-Edwards rigid ring at our institution. Degenerative disease was the most frequent cause and a small number had other conditions such as endocarditis and rheumatic disease. Ten patients were in Carpentier's functional class Type I, 101 patients in Type II and 1 patient in Type III, based on valve pathology. Ischemic mitral regurgitation was excluded. The mean follow-up time was 5.3+/-3.6 years (range: 8 days to 12.3 years). All patients were completely followed by echocardiography. RESULTS: The rigid ring ranged from 26 to 36 mm in diameter and the most common size was 30 mm. Although the mitral orifice area was decreased after mitral valve repair in all patients, none of them required reoperation because of mitral stenosis or left ventricular outflow tract obstruction (systolic anterior motion). Reduction of both systolic and diastolic left ventricular volumes was observed postoperatively. Ejection fractions were preserved in all cases. The actuarial survival rate was 92.0+/-3.0% at 10 years and the reoperation-free rate at 10 years was 96.0+/-2.0%. CONCLUSION: The rigid ring has produced promising midterm results in terms of reoperation-free and survival rates.

Adolescent↗

Prevalence of pannus formation after aortic valve replacement: clinical aspects and surgical management.

Pannus formation after aortic valve replacement is not common, but obstruction due to chronic pannus is one of the most serious complications of valve replacement. The causes of pannus formation are still unknown and effective preventive methods have not been fully elucidated. We reviewed our clinical experience of all patients who underwent reoperation for prosthetic aortic valve obstruction due to pannus formation between 1973 and 2004. We compared the initial 18-year period of surgery, when the Björk-Shiley tilting-disk valve was used, and the subsequent 13-year period of surgery, when the St. Jude Medical valve was used. Seven of a total of 390 patients (1.8%) required reoperation for prosthetic aortic valve obstruction due to pannus formation. All seven patients were women; four patients underwent resection of the pannus and three patients needed replacement of the valve. The frequency of pannus formation in the early group was 2.4% (6/253), whereas it was 0.73% (1/137) in the late group (P < 0.05). Pannus was localized at the minor orifice of the Björk-Shiley valve in the early group and turbulent transvalvular blood flow was considered to be one of the important factors triggering its growth. We also consider that small bileaflet valves have the possibility of promoting pannus formation and that the implantation of a larger prosthesis can contribute to reducing the occurrence of pannus.

Adult↗

Prevalence and avoidance of patient-prosthesis mismatch in aortic valve replacement in small adults.

BACKGROUND: It is still controversial as to whether a small prosthesis should be inserted or a small aortic annulus should be enlarged to minimize patient-prosthesis mismatch (PPM). This retrospective study reviewed our strategy for avoiding PPM. METHODS: Isolated or combined aortic valve replacement was performed in 181 patients, including 24 patients (13.3%) aged less than 65 years with a small aortic annulus (< or = 21 mm) who underwent enlargement of the annulus by the Manouguian (n = 18) or Nicks (n = 6) procedure. In patients aged 65 years or more, a Carpentier-Edwards Perimount pericardial (CEP) valve was implanted with few exceptions. We assessed our strategy for avoiding PPM by comparison with published normal reference values for the indexed effective orifice area. RESULTS: A CEP valve was implanted in 53 patients, and St. Jude Medical (SJM) mechanical valves were used in 128 patients. A standard 21-mm SJM valve was only used in 4 patients and no 19-mm valves were employed. However, 19-mm CEP valves were used in 12 older patients with a small body surface area (1.43 +/- 0.14 m2). No patient receiving an SJM valve had an indexed effective orifice area of 0.85 cm2/m2 or less, and PPM developed in only 2 (3.8%) of 53 patients receiving CEP valves. Consequently, the prevalence of PPM was 1.1%. The 10-year survival rates of patients receiving CEP or SJM valves with or without annular enlargement were similar. CONCLUSIONS: The prevalence of PPM was low in patients more than 65 years old with a relatively small body size who received bioprosthetic valves. In patients less than 65 years old with a small annulus, the method of first choice for avoiding PPM is aortic annular enlargement.

Adolescent↗

Long-term results of triple-valve procedure.

Triple-valve procedures are associated with high early and late mortality. We reviewed our experience in 25 patients who underwent combined mitral and aortic valve replacement with tricuspid valve repair or replacement between 1979 and 2004. The mean follow-up was 7.8 years (range, 10 days to 24.5 years). The mean age at operation was 52 years (range, 31 to 72 years). Four patients underwent triple-valve replacement and 21 had double-valve replacement and tricuspid annuloplasty. Perioperative mortality was 20% and late mortality was 24%. Cumulative survival, calculated taking perioperative mortality into account, was 71% +/- 10% at 10 years and 36% +/- 15% at 15 years after surgery. Only 1 of 20 perioperative survivors required re-operation for prosthetic valve dysfunction. Double-valve replacement with tricuspid annuloplasty offers satisfactory long-term survival with freedom from thromboembolism and re-operation.

Adult↗

MAGI1 recruits Dll1 to cadherin-based adherens junctions and stabilizes it on the cell surface.

Delta-Notch signaling plays an essential role in cell fate determination in many tissue types, including the central nervous system. Although the signaling mechanism of Notch has been extensively studied, the behaviors of its ligands are not well understood. In the present study, we found that, in the developing neural tube, Dll1(Delta-like 1) was mainly localized on the processes extending from nascent neurons toward both the pia and the ventricle and accumulated at apical termini, where adherens junctions (AJs) were formed. To understand the mechanism of Dll1 localization, we searched for binding proteins for Dll1 and identified a scaffolding molecule, MAGI1. In the developing spinal cord, MAGI1 mRNA was highly expressed in the ventricular zone, where Dll1 mRNA was expressed. MAGI1 protein accumulated at the AJs formed around the termini of apically extending processes and was partially colocalized with Dll1. MAGI1 bound not only to Dll1 but also to N-cadherin-beta-catenin complexes. In cultured AJ-forming fibroblasts, MAGI1 was localized at AJs, and Dll1 was recruited to these AJs through binding to MAGI1. In addition, Dll1 was stabilized on the cell surface by MAGI1. Taken together, these results suggest that Dll1 is presented on the surface of AJs formed at the apical termini of processes through interaction with MAGI1 to activate Notch on neighboring cells in the developing central nervous system.

Adaptor Proteins, Signal Transducing↗

Migrating postmitotic neural precursor cells in the ventricular zone extend apical processes and form adherens junctions near the ventricle in the developing spinal cord.

Postmitotic neural precursors are generated in the ventricular zone (VZ) of the developing neural tube and immediately migrate to the mantle layer (ML) where they differentiate into mature neurons. Although the regulation of neuronal differentiation and migration has extensively been studied, the behavior of the early postmitotic precursors migrating toward the ML is largely unknown. In this study, we have identified Neph3 as a specific marker for early postmitotic neural precursors in the VZ of the developing spinal cord. Analysis of Neph3 localization by immunofluorescence and immunoelectron microscopy revealed that early neural precursors in the VZ possessed not only pia-connected processes but also ones that reached the ventricle. This apical extension of processes was confirmed by analyzing another early postmitotic marker, Dll1 mRNA, which was actively transported toward the ventricle and accumulated at the termini of the processes. Furthermore, adherens junctions (AJs) were formed around the apical end of processes extending from Neph3- and Dll1 mRNA-positive postmitotic precursors. Taken together, these observations suggest that migrating early postmitotic neural precursors in the VZ of the developing spinal cord form a neuroepithelial cell-like bipolar morphology and communicate with their neighboring cells through AJs.

Adherens Junctions↗

Carpentier-Edwards pericardial aortic valve in middle-aged patients: comparison with the St. Jude Medical valve.

OBJECTIVE: The objective of the present study was to compare long-term results of single aortic valve replacement (AVR) with mechanical (St. Jude Medical valves: standard) and biologic (the Carpentier-Edwards pericardial) prostheses. METHOD: Between 1995 and 2002, 95 patients who underwent single AVR with mechanical (n= 46) or biologic (n= 49) prostheses were enrolled in this study. The mean age at the operation was 54.0 +/- 9.6 years (range: 20 to 69 years) with the mechanical and 68.8 +/- 7.1 years (range: 44 to 85 years) with the biologic prosthesis. RESULTS: The 9-year actuarial survival rate, which was calculated by taking perioperative mortality into account, was 90.3 +/- 4.6% for patients with mechanical valves and 87.6 +/- 4.8% for patients with bioprostheses, with no difference between the two groups (p=0.342). The 9-year freedom rate from thromboembolism, reoperation, endocarditis was 94.8 +/- 3.6%, 100% and 97.8 +/- 2.2% for patients with mechanical valves and 98.0 +/- 2.0%, 97.5 +/- 3.4% and 95.0 +/- 3.4% for those with bioprostheses, respectively. After 9 years, freedom from cardiac death averaged 97.8% in the group with mechanical valves compared with 95.3% in those with bioprostheses (p=0.541). CONCLUSION: We conclude that the mid-term durability of the Carpentier-Edwards pericardial valve in the aortic position for the elderly is excellent. Nevertheless, the risk of tissue valve reoperation progressively increases with time, and a longer follow-up may be necessary to provide its value compared with the mechanical valves in a country like Japan with a high life expectancy.

Adult↗

Long-term assessment of mitral valve reconstruction with resection of the leaflets: triangular and quadrangular resection.

BACKGROUND: The procedure of quadrangular resection and suture for prolapsed posterior leaflet of the mitral valve is a reliable and reproducible method that achieves excellent long-term results. However, triangular resection and suture of a prolapsed anterior leaflet is not widely supported and different techniques have been advocated. The aim of this study was to review our experience of mitral valve repair in which resection of the anterior and/or posterior leaflets was performed. METHODS: Between October 1991 and September 2003, 105 patients with mitral regurgitation underwent mitral valve reconstruction with leaflet resection, including 55 patients with quadrangular resection of the posterior leaflet (P), 32 patients with triangular resection of the anterior leaflet (A), and 18 patients with resection of both leaflets (A+P). RESULTS: The mean follow-up period was 63.6 (1 to 139) months. Reoperation was required in 2 patients, each after resection of the anterior or posterior leaflet. The freedom from reoperation rates at 10 years in 93% +/- 5% of patients after triangular resection of the anterior leaflet, 96% +/- 3% after quadrangular resection of the posterior leaflet, and 100% after resection of both leaflets. There were no significant differences of survival or risk of reoperation among these three groups. The postoperative mitral valve area was significantly smaller than the preoperative area in all three groups, but remained large enough (A: 2.84 +/- 1.07; P: 2.6 +/- 0.87; A+P: 3.09 +/- 1.20 cm2) for adequate valve function. CONCLUSIONS: Triangular resection of a prolapsed anterior mitral leaflet is a reliable, reproducible, and durable procedure, like quadrangular resection of a prolapsed posterior leaflet.

Actuarial Analysis↗

Midterm results of Manouguian double valve replacement: comparison with standard double valve replacement.

OBJECTIVE: Surgical strategies for patients who have a small aortic annulus associated with a small mitral annulus remain controversial. The objective of this study was to assess the validity of the Manouguian procedure for double valve replacement with patch enlargement of the annuli. METHODS: We reviewed 57 consecutive patients who underwent double valve replacement for combined aortic and mitral disease between September 1991 and October 2000. Thirty patients underwent the Manouguian procedure with patch enlargement of the aortic and mitral annuli, and the other 27 patients had standard double valve replacement. The Manouguian procedure was selected for a small aortic annulus of less than 21 mm in diameter. The patients were followed for a median of 7.5 years. Results of echocardiography and the dobutamine stress test were compared postoperatively. RESULTS: Double valve replacement with the Manouguian procedure did not increase the early or midterm mortality because the survival (including operative death) at 8 years was 83% in the Manouguian group and 84% in the double valve replacement group (P = .82). The event-free rate at 8 years was 79% in the Manouguian group and 84% in the double valve replacement group (P = .6). The prostheses implanted at the aortic and mitral positions were smaller in the Manouguian group, even after annular enlargement. However, the transprosthetic gradient across the aortic valve evaluated by means of dobutamine stress echocardiography did not differ between the 2 groups, possibly because of a smaller body surface area in the Manouguian group. CONCLUSIONS: The Manouguian patch enlargement procedure is useful during double valve replacement when associated with the problem of small-valve annuli.

Adult↗

Corl1, a novel neuronal lineage-specific transcriptional corepressor for the homeodomain transcription factor Lbx1.

During development, neuronal identity is determined by a combination of numerous transcription factors. However, the mechanisms of synergistic action of these factors in transcriptional regulation and subsequent cell fate specification are largely unknown. In this study, we identified a novel gene, Corl1, encoding a nuclear protein with homology to the Ski oncoprotein. Corl1 was highly selectively expressed in the central nervous system (CNS). In the embryonic CNS, Corl1 was expressed in a certain subset of postmitotic neurons generated posterior to the midbrain-hindbrain border. In the developing spinal cord, Corl1 was selectively expressed in the dorsal horn interneurons where a homeodomain transcription factor, Lbx1, is required for proper specification. Corl1 was localized in a nuclear dot-like structure and interacted with general transcriptional corepressors. In addition, Corl1 showed transcriptional repression activity in the GAL4-fusion system, indicating its involvement in the regulation of transcriptional repression. Furthermore, Corl1 interacted with Lbx1 and cooperatively repressed transcription, suggesting that it acts as a transcriptional corepressor for Lbx1 in regulating cell fate determination in the dorsal spinal cord. Corl1 corepressor activity did not depend on Gro/TLE activity, and Gro/TLE also functioned as a corepressor for Lbx1. Thus, Lbx1 can select two independent partners, Corl1 and Gro/TLE, as corepressors. Identification of a novel transcriptional corepressor with neuronal subtype-restricted expression might provide insights into the mechanisms of cell fate determination in neurons.

Amino Acid Sequence↗

Helt, a novel basic-helix-loop-helix transcriptional repressor expressed in the developing central nervous system.

Neuronal differentiation is regulated by many basic-helix-loop-helix (bHLH) family transcriptional activators and repressors, and the balance of activity between these factors is important for the differentiation process. Here, we report the identification of a novel transcriptional repressor, designated Helt. Helt encoded a Hey-related bHLH protein containing the bHLH and Orange domains. Helt could homodimerize, and heterodimerize with Hes5 or Hey2. Both the bHLH and Orange domains were involved in the homodimerization. In contrast, only the bHLH domain was required for the heterodimerization with Hey2, whereas only the Orange domain mediated the interaction between Helt and Hes5. Thus, Helt has two dimerization domains, and these domains independently select a partner. Identification of preferred recognition sequences by CASTing experiments revealed that Helt bound to the E box, which was distinct from the Hes1 optimal sequence around the E box core. Not only the core sequence but also sequences flanking the E box were essential for the recognition by Helt and Hes1. Furthermore, Helt repressed transcription from an artificial promoter through binding to the optimal E box elements, as well as transcription from its own promoter. Using in situ hybridization and immunohistochemistry, Helt expression in embryos was investigated. Helt was mainly expressed in undifferentiated neural progenitors in some of the developing brain regions, including the mesencephalon and diencephalon, at the neurogenesis stage. These results suggest that Helt acts as a transcriptional repressor to regulate neuronal differentiation and/or identity.

Amino Acid Sequence↗

[Suppression of neutrophil immune function in rabbit models of hemorrhagic shock complicated by intra-abdominal hypertension].

OBJECTIVE: To investigate the effects of hemorrhagic shock and intra-abdominal hypertension (IAH) on inflammatory responses of peripheral circulating neutrophils such as intracellular cytokine production, phagocytic capacity and expression of nuclear factor (NF)- kappaB. METHODS: Twenty-four rabbits were divided equally into 4 groups including a hemorrhagic shock (HS) group complicated by abdominal compartment syndrome (ACS) (Group A), a HS group (Group B), a ACS group (Group C) and a normal control group (Group D). Intracellular interleukin (IL)-8 production in the peripheral neutrophils were measured in the rabbits by flow cytometry, phagocytic function of the neutrophils evaluated by a chemiluminescence method and the NF-kappaB expression detected by immunocytochemistry before, immediately and 4 h after the traumatization. RESULTS: Four hours after the trauma, decreased intracellular IL-8 production and impaired phagocytic function of the peripheral neutrophils were observed in Group A along with suppressed NF-kappaB expression. But in Group B and Group C, the intracellular IL-8 production, phagocytic function and expression of NF-kappaB returned to the normal levels 4 hours after the trauma following the early-stage changes. In Group D, no significant changes occurred during the observation. CONCLUSIONS: Responsiveness and function of the neutrophils to the stimuli by endotoxin are suppressed by the sequential second-hit of IAH after hemorrhagic shock, which may contribute to the occurrence of sepsis in ACS.

Abdomen↗

Prevention of primary nonfunction of canine islet autografts by treatment with pravastatin.

BACKGROUND: Nonspecific inflammation is the primary cause of early islet graft loss. We have shown in mice that pravastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, prevents primary nonfunction of islet isografts by reducing inflammatory reactions at the graft site. This study was designed to test the effectiveness of this agent in a large animal model, dogs, by transplanting autologous islets. METHODS: After total pancreatectomy, islets were isolated by using a two-step digestion method, followed by discontinuous gradient centrifugation on EuroFicoll. A known number of freshly isolated islets were immediately transplanted back into the same dog via the portal vein. RESULTS: First, we determined the minimal islet number required to reverse diabetes by transplanting 3,000-10,000 IEQ/kg with no additional treatment. The number was found to be 4,000 IEQ/kg, and islets less than 4,000 IEQ/kg consistently failed. To test the effect of pravastatin, 3,000 IEQ/kg were transplanted into dogs that either received no further treatment or were treated daily with 20 mg/kg of pravastatin from days -2 to 14. Without pravastatin, this number of islets lowered blood glucose only transiently, and all four of these dogs became hyperglycemic within 1 week. In contrast, four of the five dogs treated with pravastatin became normoglycemic (<150 mg/dL) and maintained this level during the observation period of 12 weeks (P<0.05). Postprandial plasma glucose and insulin levels returned to normal, and K values of intravenous glucose tolerance tests were significantly higher in pravastatin-treated dogs than in controls (P<0.04 at week 2 and P<0.01 at week 4). CONCLUSION: Peritransplant pravastatin treatment reduced the number of autologous islets required to reverse diabetes in totally pancreatectomized dogs. These results suggest that pravastatin may also facilitate better islet graft survival and function in clinical transplantation.

Animals↗

Identification of activity-regulated proteins in the postsynaptic density fraction.

BACKGROUND: The postsynaptic density (PSD) at synapses is a specialized submembranous structure where neurotransmitter receptors are linked to cytoskeleton and signalling molecules. Activity-dependent dynamic change in the components of the PSD is a mechanism of synaptic plasticity. Identification of the PSD proteins and examination of their modulations dependent on synaptic activity will be valuable for an understanding of the molecular basis of learning and memory. RESULT: We attempted here to identify proteins in the PSD fraction by two-dimensional (2D) gel electrophoresis and mass spectrometry. About 1.7 x 103 protein spots were detected on 2D gels. A total of 90 spots were identified, containing 47 different protein species. In addition to previously identified PSD proteins such as PSD-95/SAP90, several new proteins were identified in the PSD fraction. They included stomatin-like protein 2 and NIPSNAP1. We also examined activity-dependent modulations of PSD proteins by 2D gel electrophoresis. The spot concentration of G protein beta subunit 5 and NIPSNAP1 increased 2 h after kainate treatment that caused generalized seizures. CONCLUSION: These results indicate that the combination of 2D gel electrophoresis and mass spectrometry is an excellent tool for the identification of activity-regulated PSD proteins.

Animals↗

Effects of leukocyte-depleted reoxygenation on endothelial and ventricular function: with observation of a short time period.

Postoperative myocardial global dysfunction causes mortality and morbidity in cyanotic congenital defects. This study investigates whether leukocyte depletion during coronary perfusion following reoxygenation can maintain endothelial and myocyte function, or less oxidant damage in a porcine neonatal model. After 30 minutes hypoxemia, 13 piglets underwent 60 minutes reoxygenation. The aorta was clamped and coronary reperfusion was either with normal blood (N=6), or leukocyte free blood by an inline filter (N=7). Cardiac function and endothelial response were assessed before and after cardiopulmonary bypass (CPB). Contractile recovery was improved by leukocyte depletion. Additionally, the antioxidant reserve capacity reserved more (534 36 versus 772 91; p<0.05) than reoxygenation without a leukocyte-depleting filter. Leukocyte depletion returned more extreme relaxation to acetylcholine (71.8 20.4% versus 41.2 9.8%; p<0.05), but did not change the endothelium-independent relaxation to sodium nitroprusside in either group. Activated leukocytes release oxygen free radicals that play a role in deterioration of the endothelial/myocardial function after reoxygenation and this deterioration in cyanotic heart diseases may be avoided by the use of the leukocyte-depleting filter.

Animals↗