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Biomedical subjects

S Miyamoto

Publications and source records attributed to S Miyamoto.

At least 91 records · Page 5Linked to original sources
PubMed2001

Lysophosphatidylcholine induces early growth response factor-1 expression and activates the core promoter of PDGF-A chain in vascular endothelial cells.

Lysophosphatidylcholine (lyso-PC), a polar phospholipid that is increased in atherogenic lipoproteins and atherosclerotic lesions, has been shown to transcriptionally induce the expression of endothelial genes relevant to atherogenesis. In cultured bovine aortic endothelial cells (BAECs), we show that lyso-PC induces the expression of early growth response factor (Egr)-1 and thereby activates the proximal promoter of the platelet-derived growth factor (PDGF)-A chain located 55 to 71 bp upstream from the transcription start site, which has been shown to be crucial for PDGF-A chain expression induced by fluid shear stress and fibroblast growth factor-1. Northern blot analyses showed that lyso-PC (10 to 20 micromol/L) transiently (30 minutes to 1 hour) induced expression of Egr-1 mRNA. Induced expression of Egr-1 mRNA, which was associated with increased amounts of Egr-1 protein in nuclei, preceded PDGF-A chain mRNA induction in lyso-PC-activated BAECS: Nuclear runoff assay revealed that lyso-PC stimulates transcription of the Egr-1 gene. Transient transfection of the oligonucleotide corresponding to the proximal promoter of the PDGF-A chain (oligo A) linked to the luciferase reporter gene revealed that lyso-PC can activate the core promoter of the PDGF-A chain by 5-fold. Insertion of a guanine at 3 sites in the oligo A abolished the lyso-PC-induced increases in luciferase activities. Electrophoretic mobility shift assay with use of radiolabeled oligo A showed a lyso-PC-inducible shift band, which was suppressed by excess amounts of unlabeled oligo A or an anti-Egr-1 antibody. In addition, lyso-PC-induced Egr-1 expression was inhibited by PD98059, a specific inhibitor of mitogen-activated protein kinase kinase-1 (MEK1), suggesting that lyso-PC-induced expression of Egr-1 depends on the MEK1/extracellular signal-regulated kinase pathway. Taken together, transcriptional activation of Egr-1-dependent genes by this atherogenic lipid may be a key regulator of atherogenesis.

Animals↗
PubMed2001

Oxidized LDL modulates Bax/Bcl-2 through the lectinlike Ox-LDL receptor-1 in vascular smooth muscle cells.

Oxidized low density lipoprotein (Ox-LDL) induces apoptosis in vascular smooth muscle cells (VSMCs), which may increase atherosclerotic plaque instability. In this study, we examined the molecular mechanisms causing the Ox-LDL-induced apoptosis in VSMCs, especially focusing on the involvement of Bax/Bcl-2 and the lectinlike Ox-LDL receptor-1 (LOX-1). In cultured bovine aortic smooth muscle cells (BASMCs), Ox-LDL at high concentrations (>60 microg/mL) induced cell death as demonstrated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. DNA fragmentation was increased in BASMCs treated with high concentrations of Ox-LDL, indicating that the Ox-LDL-induced cell death in VSMCs was apoptosis. Ox-LDL upregulated LOX-1 expression through phosphorylation of extracellular signal-regulated kinase in BASMCs, and a neutralizing anti-LOX-1 monoclonal antibody, which can block LOX-1-mediated cellular uptake of Ox-LDL, prevented the Ox-LDL-induced apoptosis in BASMCs. This antibody also suppressed the increase in the Bax to Bcl-2 ratio induced by Ox-LDL in BASMCs. Furthermore, LOX-1 expression was well colocalized with Bax expression in the rupture-prone shoulder areas of human atherosclerotic plaques in vivo. LOX-1 may play an important role in Ox-LDL-induced apoptosis in VSMCs by modulating the Bax to Bcl-2 ratio. These molecular mechanisms may be involved in destabilization and rupture of atherosclerotic plaques.

Animals↗
PubMed2001

Increased autoantibodies against oxidized low-density lipoprotein in coronary circulation in patients with coronary spastic angina.

Oxidized low-density lipoproteins are important in the progression of atherosclerosis. Autoantibodies against malondialdehyde-modified low-density lipoproteins have been reported to be predictive of the progression of atherosclerosis. This study sought to examine whether plasma levels of autoantibodies against oxidized low-density lipoprotein increase in the coronary circulation in patients with coronary spastic angina. The authors examined plasma antioxidized low-density lipoprotein antibody levels (activity unit values (AcU)/mL) simultaneously in the coronary sinus and the aortic root in 20 patients with coronary spastic angina, 23 patients with stable exertional angina, and 15 control subjects by measuring plasma levels of immunoglobulin G (IgG) autoantibodies against malondialdehyde-modified low-density lipoproteins by enzyme-linked immunosorbent assay. The plasma antioxidized low-density lipoprotein antibody levels (AcU/mL) in the coronary sinus increased in coronary spastic angina (38 +/- 16) compared with stable exertional angina (23 +/- 7) and control subjects (20 +/- 6) (p < or = 0.0001). The levels (AcU/mL) in the aortic root also increased in coronary spastic angina (33 +/- 12) compared with stable exertional angina (23 +/- 7) and control subjects (20 +/- 6) (p < 0.005). Furthermore, the coronary sinus-arterial differences of the levels (AcU/mL) were also higher in coronary spastic angina (5 +/- 9) than in stable exertional angina (0 +/- 6) and healthy subjects (-1 +/- 5) (p < 0.05). The generation of malondialdehyde-modified low-density lipoproteins is reported to be associated with atherothrombosis. These findings suggest that elevated levels of autoantibodies against malondialdehyde-modified oxidized low-density lipoproteins in coronary circulation are associated with the development of atherothrombosis from the progression of atherosclerosis rather than with the extent of coronary atherosclerosis in patients with coronary spastic angina.

Acetylcholine↗
PubMed2001

N-WASP, WAVE and Mena play different roles in the organization of actin cytoskeleton in lamellipodia.

WASP- and Ena/VASP-family proteins have been reported to regulate the cortical actin cytoskeleton as downstream effectors of the Rho-family small G-proteins Rac and Cdc42, but their functions are little understood. We observed the localization of the WASP family proteins, N-WASP and WAVE, and the Ena/VASP family protein, Mena, in protruding lamellipodia. Rat fibroblast cell line 3Y1 protruded lamellipodia on poly-L-lysine-coated substrate without any trophic factor. N-WASP and Cdc42 were concentrated along the actin filament bundles of microspikes but not at the tips. By immunofluorescence and immunoelectron microscopy, both WAVE and Mena were observed to localize at the lamellipodium edge. Interestingly, Mena tended to concentrate at the microspike tips but WAVE did not. At the edge of the lamellipodium, the correlation between the fluorescence from Mena and actin filaments stained with the specific antibody and rhodamine-phalloidin, respectively, was much higher than that between WAVE and actin filament. The Ena/VASP homology 2 (EVH2) domain of avian Ena, an avian homolog of Mena, was localized to the lamellipodium edge and concentrated at the tip of microspikes. The SCAR homology domain (SHD) of human WAVE was distributed along the lamellipodium edge. These results indicate that N-WASP, WAVE and Mena have different roles in the regulation of the cortical actin cytoskeleton in the protruding lamellipodium. WAVE and Mena should be recruited to the lamellipodium edge through SHD and the EVH2 domain, respectively, to regulate the actin polymerization near the cell membrane. N-WASP should regulate the formation of the actin filament bundle in addition to activating Arp2/3 complex in lamellipodium under the control of Cdc42.

Actins↗
PubMed2001

Late reperfusion (6-24 hours after onset) improves left ventricular function in patients with acute myocardial infarction.

The TAMI-6 trial has demonstrated that coronary reperfusion >6h after onset (ie, late reperfusion) in patients with acute myocardial infarction (AMI) does not improve left ventricular (LV) function during the chronic phase of infarction. However, the low patency rate (only 60%) of the infarct-related artery (IRA) during the chronic phase in the TAMI-6 trial raises a new hypothesis that late reperfusion with a higher patency rate may improve LV function during the chronic phase. Forty-four patients with AMI, who were admitted to hospital 6-24h after the symptom onset and in whom emergency coronary angiography revealed a total occlusion of the IRA, were randomly assigned to either the late reperfusion group (n=22) or the non-reperfusion group (n=22). The initial success rate of reperfusion therapy in the late reperfusion group was 86% and the chronic patency rate of the IRA was 91%. The improvements in ejection fraction and chord shortening in the infarct region from the acute phase to the chronic phase were significantly greater in the late reperfusion group than in the non-reperfusion group. Late reperfusion with a high patency rate of the IRA significantly improves LV global and regional function in patients with AMI.

Adult↗
PubMed2001

Species- and temperature-dependency of the decrease in myofilament Ca2+ sensitivity induced by beta-adrenergic stimulation.

Although beta-adrenergic stimulation has been shown in many studies to decrease myofilament Ca2+ sensitivity in various types of cardiac muscle such as rat and rabbit ventricles, other studies disagree with this conclusion. In the present study, we aimed to explain these contradictory findings. We examined the effect of beta-adrenoceptor stimulation on Ca2+ sensitivity using guinea pig and rat ventricles. We performed the experiment at two different temperatures and compared the results. In guinea pig ventricles, isoproterenol and forskolin did not alter the relationship between [Ca2+]i and muscle force during the relaxation phase of tetanic contraction at either 24 degrees C or 30 degrees C. In rat ventricles, in contrast, isoproterenol shifted the [Ca2+]i-force curve to the right at 24 degrees C, but not at 30 degrees C. In guinea pig ventricles permeabilized by alpha-toxin, in which the cAMP/PK-A system is intact, the addition of cAMP did not decrease Ca2+ sensitivity. These results suggest that there are species- and temperature-dependent differences in the regulation of myofilament Ca2+ sensitivity by beta-adrenergic stimulation.

Actin Cytoskeleton↗
PubMed2001

Slowing Na+ channel inactivation prolongs QT interval and aggravates adrenaline-induced arrhythmias.

We investigated the effects of prolonged repolarization induced by slowed inactivation of Na+ channel on adrenaline-induced arrhythmias in halothane anesthetized, closed-chest dogs. We used sea anemone toxins (ATX-II and Anthopleurin-A) to prolong ventricular repolarization and examined their effects on adrenaline arrhythmias. Sea anemone toxins prolonged the QTc- and JTc-intervals (P<0.01), but did not affect the PQ interval, QRS duration, heart rate and mean blood pressure. Although sea anemone toxins did not induce any arrhythmias by themselves, under the treatment with these toxins, arrhythmias were induced by non-arrhythmia-inducing doses of adrenaline in four dogs out of seven and the control arrhythmias induced by adrenaline were aggravated. These results indicate that, similar to the inhibition of K+ channels by class III drugs, which we have already reported, slowing Na+ channel inactivation with QTc prolongation also aggravates adrenaline-induced arrhythmias.

Animals↗
PubMed2001

Liver segment S2 is consistently located at the dorsal side of S3 but sometimes at the right and/or caudal side of S3.

After preparing the frontal section including the origin of the left portal trunk at the hilar region, the left anatomical lobes of 111 human livers were dissected to reveal the segmental configuration based on the supplying portal vein branches. S2 was consistently located dorsal to S3. However, in contrast to the description in common textbooks for medical students, 19.8% of the specimens carried a paradoxical segmental configuration showing a "caudal and/or rightward" S2 in combination with a "cranial and/or leftward" S3 in the frontal section through the ventral part of the hilar region. The caudal and rightward cases were associated with a specific arrangement of S2 and S3 segmental stems in which the S3 stem ran relatively upward to spread over S2 or both stems ran almost horizontal, respectively. In routine diagnostic radiology, identification of S2 and S3 might sometimes be biased by the generally accepted notion that S2 should be located at the dorsal, cranial and left side of S3.

Humans↗
PubMed2001

Distribution of genes for bone morphogenetic protein-4, -6, growth differentiation factor-5, and bone morphogenetic protein receptors in the process of experimental spondylosis in mice.

OBJECT: Because little is known about the molecular mechanisms underlying the process of spondylosis, the authors examined the extent of genetic localization of several members of bone morphogenetic protein (BMP) and BMP receptors in chondrogenesis during the process of inducing spondylosis in their previously established experimental mice model. METHODS: Experimental spondylosis was induced in 5-week-old ICR mice. The cervical spine was harvested chronologically, and histological sections were prepared. Messenger RNA for BMP-4, growth and differentiation (GDF)-5, BMP-6, and BMP receptors (ALK-3, -6, and BMP-RII) was localized in the tissue sections by in situ hybridization. In the early stage, BMP-4-derived mRNA was localized mainly in cells in the anterior margin of the cervical discs, together with ALK-6 and BMP-RII mRNA. No GDF-5 and BMP-6 mRNA was detected at this stage. In the late stage, cells positive for BMP-4 decreased, whereas GDF-5 and BMP-6 mRNA were localized in cells undergoing chondrogenesis. The ALK-3 mRNA began to appear in this stage, as did ALK-6 and BMP-RII. CONCLUSIONS: The localization of transcripts for BMP-4, -6, and GDF-5 as well as BMP receptors shown during the present experimental model indicate the possible involvement of molecular signaling by these BMPs in the chondrogenic progress in spondylosis.

Animals↗
PubMed2001

Discrepancies between the gene expression, protein expression, and enzymatic activity of thymidylate synthase and dihydropyrimidine dehydrogenase in human gastrointestinal cancers and adjacent normal mucosa.

The relationships between gene expression, protein expression, and enzymatic activity of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) have not been clarified in tumor and non-tumor tissues of human. In this study, we compared three different parameters by evaluating TS and DPD levels, mRNA expression assessed by RT-PCR, protein expression evaluated by immunohistochemical examination, and enzymatic activity measured by biochemical assay, in the tumor tissue and adjacent normal mucosa of 43 patients with gastrointestinal cancer. TS enzymatic activity in the tumor tissue was significantly higher than in normal tissue in both the stomach (median activity: 81.0 and 38.0 pmol/mg protein, respectively, p=0.012) and the colorectum (49.8 and 30.8, respectively, p=0.023). Similarly, TS mRNA expression in the tumor tissue was significantly higher than in normal tissue in both the stomach (median TS/GAPDH ratio: 6.0 and 2.0, respectively, p=0.009) and the colorectum (3.20 and 0.91, respectively, p=0.001). But no significant differences in DPD activity were observed between the tumor and normal tissue in either stomach (median activity: 41.3 and 41.6 pmol/min/mg protein, respectively) or colorectum (34.9 and 49.0, respectively). On the other hand, DPD mRNA levels in normal tissue were significantly higher than in tumor tissue only in the colorectum (DPD/GAPDH ratio: 0.83 and 0.20, respectively, p=0.003). No linear relationships were found between the enzymatic activity and mRNA expression of TS or DPD either in tumor or normal tissue. Nor were any correlations found between protein expression and either mRNA expression or enzymatic activity for either TS or DPD. These results suggest that tissue TS and DPD levels may vary with differences in the methods used to measure them. These discrepancies must be taken into account when interpreting correlation between TS and DPD levels and clinical outcome.

Aged↗
PubMed2001

[A case report of Ebstein's anomaly treated with Hetzer's procedure].

A 27-year-old male who had been diagnosed with Ebstein's anomaly was admitted with uncontrollable congestive heart failure. The echocardiogram revealed severe tricuspid valve incompetence and the electrocardiogram showed atrial fibrillation. He underwent Hetzer's repair procedure for tricuspid valve incompetence and Minzioni's right atrial isolation technique to restore sinus rhythm. His congestive heart failure quickly disappeared and sinus rhythm was restored after operation. He was discharged 3 weeks postoperatively and remains well 22 months after his operation. Hetzer's technique for tricuspid valve repair in Ebstein's anomaly restructures the valve mechanism at the level of the true tricuspid anulus by using the most mobile leaflet for valve closure without plication of the atrialized chamber. We conclude that Hetzer's procedure is an effective operation for Ebstein's anomaly.

Adult↗
PubMed2001

Biodegradable poly-D,L-lactic acid-polyethylene glycol block copolymers as a BMP delivery system for inducing bone.

BACKGROUND: Bone morphogenetic proteins (BMPs) are biologically active molecules capable of eliciting new bone formation. In combination with biomaterials, these proteins can be used in a clinical setting as bone-graft substitutes to promote bone repair. Collagen from animal sources has previously been the preferred carrier material in animal experiments. More recently, synthetic biodegradable polymers have been tested as a delivery vehicle for osteoinductive agents. In earlier studies performed in our laboratory, it was found that the polylactic acid homopolymers (PLA650) and poly-D,L-lactic acid-polyethylene glycol block copolymers (PLA650-PEG200) are viscous liquids that can be used as BMP delivery systems. METHODS: To obtain new PLA-PEG polymers that exhibit greater plasticity, the molecular sizes of PLA and PEG segments in the copolymer chains were increased. Plastic PLA-PEG polymers with various molecular sizes and PLA/PEG ratios were synthesized, mixed with recombinant human (rh) BMP-2, and implanted into the dorsal muscles of mice for 3 weeks to evaluate their capacity to elicit new bone formation. To compare the plastic PLA-PEG polymer with the liquid PLA650-PEG200 polymer, these two polymers were combined with rhBMP-2, implanted, and harvested after 3 weeks. Bone mineral content (BMC), bone area, and bone mineral density (BMD) of the ectopic new bone were measured by means of single energy X-ray absorptiometry (SXA). RESULTS: All of the PLA6,500-PEG3,000 implants with 10 or 20 microg of rhBMP-2 showed new bone formation. In contrast, little or no bone formation was seen in other plastic PLA-PEG implants with rhBMP-2. Control implants that lacked rhBMP-2 did not show new bone formation. Radiographic and histologic examinations showed that the PLA6,500-PEG3,000 implants with rhBMP-2 harvested 3 weeks after implantation had normal bone characteristics with hematopoietic marrow and osseous trabeculae. SXA analysis showed that the values for bone mineral content (BMC), bone area, and bone mineral density (BMD) of new bone resulting from the use of plastic PLA6,500-PEG3,000 polymers with rhBMP-2 were significantly higher than those obtained with the liquid PLA650-PEG200 polymers (p < 0.001 for each of the three values). CONCLUSIONS: These results indicate that the PLA6,500-PEG3000 block copolymer with plastic properties works effectively as a BMP delivery system. These data suggest that the total molecular size and ratio of PLA size to PEG size is an essential factor in determining the efficacy of a BMP delivery system. After implantation, it is possible that the PLA6,500-PEG3,000 pellets might have absorbed tissue fluids and become swollen, resulting in bone formation that exceeded the size of the original implants. This expansion characteristic is a potentially beneficial property, given the intended practical application of the polymer in the repair of bone defects. CLINICAL RELEVANCE: New synthetic biodegradable delivery systems will play an important role in the clinical applications of rhBMPs in which local formation of bone via an osteoinductive graft material is needed. Further pre-clinical and clinical work is necessary to establish the safety of these implants before they are adopted for widespread clinical use.

Animals↗
PubMed2001

[Configuration of the liver segment observed in the frontal section including the origin of the left portal trunk at the hepatic hilum].

After preparing threparing the frontal section including the origin of the left portal trunk at the hepatic hilum, 60 human livers (35, entirely; 25, partly) were dissected to reveal segmental configuration and the supplying portal vein branches. We usually observed two combinations of segments, i.e., S2, 4, 5 and 8 or S2, 3, 4, 5 and 8, in the frontal section including the origin of the left portal trunk. However, S8 was sometimes absent in the section when S4 extended to the right and/or upper side. S2 was consistently located dorsal to S3 despite the fact that 11.7% of the specimens carried an unexpected configuration showing a "lower" S2 in combined with an "upper" S3 in the frontal section. The latter case was associated with specific S2 and S3 segmental branches maintaining horizontal courses along a common plane. S4, S5 and S8 were usually arranged from the ventral to the dorsal aspect in this order. Four types of ventral short branches originated at or near the primary portal divisions and supplied the hilar parenchyme adjacent to S4 and/or the anterior segment (S5 or S8). These ventral short branches tended to be associated with the variations of the primary division. Dissection of the liver after frontal section provided a better understanding of the segmental configuration rather than an approach from the hepatic hilum.

Aged↗
PubMed2001

A method for assessing the side chain orientations of histidine, asparagine, and glutamine as well as the protonation forms of histidine in protein structures.

In protein X-ray crystallography, it is sometimes impossible to distinguish N and O in amide side chains and N and C in His side chains, resulting in the 'flipped' conformations in these side chains. We have developed a simple, but effective, approach to assess the side chain orientations of His. Asn, and Gln as well as the protonation forms of His in protein structures. This method finds the most favorable side chain orientation and His form by calculating the van der Waals interaction and hydrogen bonding energies around each residue in question. This evaluation is repeated until consistent results are obtained. Our approach was applied to four proteins and in overall approximately 25% of His, Asn, and Gln were evaluated as 'flipped' and 63% of the imidazole rings were suggested to have a polar hydrogen atom only on N epsilon2. In the individual cases, it was found that our results were comparable to or even better than those obtained by a traditional method. The present approach is therefore quite useful to construct initial protein structures for the molecular modeling studies.

Aldehyde Reductase↗
PubMed2001

Conformational analysis of cyclophostin and designed analogs in comparison with the potent IP3 receptor agonist adenophostin A.

A conformational analysis of 5'-6"-tethered cyclophostin was carried out in comparison with the mother compound, adenophostin A, which has a potent IP3 receptor agonistic activity. The global minimum 3'-endo/anti conformation of cyclophostin elucidated by a molecular dynamics simulation was in accord with NMR spectroscopic data. In contrast, the 2'-endo/syn conformation was dominant with respect to adenophostin A. Despite the constraint introduced by the tether, the spatial arrangement of the three phosphate groups and the adenine moiety, which are essential for the extremely high potency, was changed only moderately in comparison with adenophostin A. The observed high potency of cyclophostin (EC50 = 38 nM) also indicates that it closely resembles the bioactive conformation of adenophostin A (EC50 = 7 nM). These results led us to estimate the probable active conformation of adenophostin A by comparison with the stable conformations of cyclophostin. Finally, two other tethered analogs were designed and are expected to exhibit high potencies comparable to adenophostin A.

Adenosine↗
PubMed2001

[A child case of subarachnoid hemorrhage triggered by head injury: a case report].

We report a case of basal subarachnoid hemorrhage in a child. The etiology of this lesion was difficult to diagnose. The patient was a 9-year-old boy. He sustained minor head injury followed by loss of consciousness and cardiopulmonary arrest. He was brought to our emergency room by ambulance. On arrival, he presented with cardiopulmonary arrest and deep comatose state. Basal subarachnoid hemorrhage was revealed on CAT scan. 3D-CTA documented two bulging portions: one was at the junction between the left vertebral artery and the left posterior inferior cerebellar artery. The other one was shown at the basilar artery. He died on the 7th hospital day. The autopsy revealed a laceration of the left vertebral artery. Microscopically, the wall around the laceration showed a defect in the internal elastic membrane and a decrease of smooth muscle cells with moderate fibrosis in the tunica media. These findings were compatible with the structure of a congenital aneurysm. Hence, the patient was strongly suspected to have had a congenital aneurysm whose rupture was triggered by minor head injury.

Aneurysm, Ruptured↗
PubMed2001

Early and long-term results of cardiovascular surgery in octogenarians.

The purpose of this study was to evaluate characteristics and outcomes of octogenarians undergoing cardiovascular surgery with cardiopulmonary bypass in a Japanese population. Thirty-one consecutive patients over 80 years of age underwent coronary artery bypass grafting 19 (61%), combined coronary artery bypass grafting and ventricular septal perforation closure 1 (3%), valve replacement 3 (10%), and prosthetic graft replacement 8 (26%). The early mortality rate was 16.1%. Survival estimates were 74% after 1 year, 74% after 3 year, and 64% after 5 years. Emergency and urgent cases involved 16 (51.6%), and 2 patients (6.5%), respectively. Multivariate analyses revealed that predictors of early mortality was preoperative left ventricular ejection fraction. Predictors of hospital death (within 3 months after surgery) were preoperative renal dysfunction, intraaortic balloon pumping, and age. Predictors of late mortality were chronic lung disease and age. Twenty-one patients expected to have died before surgery were living at home, and 9 (40.9%) patients were completely autonomous. Multivariate analyses revealed diabetes mellitus and a small number of bypass grafts were predictive risk factors for postoperative autonomy. Thus, cardiovascular surgery can be performed in octogenarians under 85 years of age with a favorable long-term outcome, when appropriately applied in selective octogenarians without significant comorbidity. If patients are over 85 years of age or have significant comorbidity, clinical treatment recommendations should be individually tailored while evaluating the risk of having or not having surgery and their life expectancy. QOL of survivors was almost satisfactory and significantly improved compared with a preoperative state.

Age Factors↗