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Biomedical subjects

Y Iida

Publications and source records attributed to Y Iida.

At least 19 recordsLinked to original sources

Cimetidine reduces impairment of cellular immunity after cardiac operations with cardiopulmonary bypass.

OBJECTIVE: Depressive effects of cardiopulmonary bypass on cell-mediated immune responses may lead to postoperative infectious complications. We previously reported that cimetidine reduced postbypass depression of the cytotoxic activity of natural killer cells. This study evaluated cimetidine as an agent to preserve cellular immunity after cardiac operations. METHODS: In a prospective randomized study, 20 patients were divided into two groups of equal size. Cimetidine-group patients received 400 mg of cimetidine intravenously before bypass and a 33 mg/hr intravenous infusion of cimetidine after the operation, continuing until the fifth postoperative day. Control-group patients received conventional perioperative therapy. Lymphocyte subsets, natural killer cell activity, percentage of CD56+CD16+ (percentage of natural killer cells), and percentage of CD11b+CD8+ (percentage of suppressor T lymphocytes) were measured perioperatively. RESULTS: Although temporary postoperative reductions in percentages of CD3+, CD4+, and CD56+CD16+ cells were observed in both groups, CD8+ percentages on postoperative day 1 and CD11b+CD8+ percentages on postoperative days 1 and 3 in the cimetidine group were significantly lower compared with those in the control group (p = 0.01,p = 0.004, andp = 0.02, respectively). Temporary postoperative reduction of natural killer cell activity was also observed in both groups, but the natural killer cell activity on postoperative day 1 in the cimetidine group (17.1%) was significantly higher (p = 0.02) than that in the control group (8.20%). CONCLUSIONS: Cimetidine counteracts depressive effects of cardiopulmonary bypass on cell-mediated immunity and may possibly reduce postoperative susceptibility to infection.

Antigens, CD

Functional quantitative analysis of the genome in cultured human mesangial cells. Technical note.

For normal physiological function, each cell tightly regulates gene expression in a specific fashion so that critical proteins are synthesized in a well-coordinated manner. Therefore, it is very important to uncover which genes are expressed in specific cells. Recent technological advances combined with rapid large-scale DNA sequencing and computerized data processing have allowed us to investigate the expression levels of a variety of transcripts in the mesangial cells, a target of injury in many forms of glomerulonephritis. Utilizing a large scale sequencing of a 3'-directed cDNA library, which allows us to avoid variable cloning efficiencies reflecting the size of cDNA, we investigated expression profiles of various molecules in cultured human mesangial cells. Among the 1,193 sequenced clones, 688 (57.7%) appeared more than once (redundant sequence group), representing 203 different species. Thirty-nine of these appeared more than three times. The most abundant mRNA was that of fibronectin, which consisted of 3.9% of the total mRNA population. Except for mitochondrial or ribosomal genes, calcyclin came next (2.5%), followed by two cytoskeletal genes, gamma-actin gene and calpactin 1 light chain gene, in addition to an amyloid precursor protein homolog (0.7%). In conclusion, we performed a molecular biological quantification of transcripts in mesangial cells. Fibronectin was the most abundantly expressed, followed by calcyclin, gamma-actin, calpactin 1 light chain, and an amyloid precursor protein homolog. We also discovered some candidate genes specific for human mesangial cells. The expression profile of the transcripts serves as an important tool in understanding the biological properties of mesangial cells.

Actins

HRA model for hypercholesterolemia based on a longitudinal health database.

To evaluate the risk factors for hypercholesterolemia, we examined 4,371 subjects (3,207 males and 1,164 females) who received medical checkups more than twice at an AMHTS in Tokyo during the period from 1976 through 1991; and whose serum total cholesterol was under 250 mg/dl. The mean follow-up duration was 6.6 years. A self-registering questionnaire was administered at the time of the health checkup. The endpoint of this study was the onset of hypercholesterolemia when the level of serum total cholesterol was 250 mg/dl and over. We compared two prognosis groups (normal and hypercholesterol) in terms of age, examination findings and lifestyle. After assessing each variable, we employed Cox's proportional hazards model analysis to determine the factors related to the occurrence of hypercholesterolemia. According to proportional hazards model analysis, total cholesterol, triglyceride and smoking at the beginning, and hypertension during the observation period were selected in males; and total cholesterol at the beginning and age were selected in females to determine the factors related to the occurrence of hypercholesterolemia.

Adult

Glutamate receptor subunits GluR5 and KA-2 are coexpressed in rat trigeminal ganglion neurons.

To determine the subunit composition of high-affinity kainate receptors in native neurons is a challenging problem because of the expression of more than one GluR subunit. In the present study the question of whether GluR5 and/or GluR6 subunits combine with KA-1 or KA-2 subunits in vivo is addressed by performing detailed physiological, pharmacological, and molecular characterization of functional kainate receptor channels in acutely dissociated trigeminal ganglion (TG) neurons. The results show that (1) smaller diameter TG neurons (<30 microm) respond to L-glutamate and kainate, and the currents gated by kainate desensitize with prolonged agonist exposure; (2) all kainate receptor subunits are detected to some extent by reverse transcriptase-PCR, whereas glutamate receptor subunits GluR5 and KA-2 are expressed at high levels in the TG; (3) there is an obvious similarity between the features of native kainate receptor channels in TG neurons and of heteromeric recombinant GluR5(R)/KA-2 channels in pharmacological properties, desensitization, rectification, ion permeability, and mean channel conductance; and (4) the age-dependent increase in GluR5 and KA-2 RNA levels in the TG is correlated well with an increased number of kainate-sensitive cells during postnatal development. Our data suggest that the heteromeric GluR5/KA2 combination actually occurs in TG neurons and give a clue as to the subunit composition of native kainate receptor channels.

Animals

Immunocytochemical detection and spatial distribution of myosin light-chain kinase in preimplantation mouse embryos.

As a follow-up to our previous study on the role of myosin light-chain kinase (MLCK), a Ca2+/calmodulin-dependent enzyme, in the development of preimplantation mouse embryos, we examined the presence and pattern of distribution of MLCK during preimplantation development of the mouse by whole-mount, indirect immunocytochemistry and by Western blotting, using a monoclonal antibody against MLCK. At all stages of preimplantation development, the nucleus was brightly stained with an unstained region around the nucleus, and regions near the cell membrane were also brightly stained. Using the optical sectioning capability of the confocal laser scanning microscope, we found that, up to the eight-cell stage, the regions of cell contact were mostly unstained, but along with the process of compaction, cell contact regions showed a clear staining pattern along with clearing of the cytoplasm. During formation of the blastocyst, a ring of immunofluorescence was found at the margin of the blastocoel. In the blastocyst, cells of the inner cell mass were less immunofluorescent than trophectoderm cells. These staining results appear to be due to specific immunoreaction between MLCK and the antibody, because the staining patterns were abolished when the antibody was preabsorbed by MLCK purified from chicken gizzard smooth muscle. In Western blotting of blastocysts, we found a band at 130 kD. We also show by immunoblotting and immunohistochemistry of various mouse tissues that the antibody used in this study has cross-reactivity to MLCK of various muscle and non-muscle tissues of the mouse. The presence and spatial distribution of MLCK at various stages of preimplantation development of the mouse suggest that it could play a crucial role in the regulation of the contractile events involved in the initial differentiation that occurs during formation of the mouse blastocyst.

Animals

Subclinical Graves' disease as a cause of subnormal TSH levels in euthyroid subjects.

In order to elucidate causes of subclinical thyrotoxicosis, we reviewed records of thyroid function tests obtained in our hospital between 1990 and 1992 showing normal thyroid hormones and subnormal TSH levels, and analyzed underlying clinical conditions of the patients. Of 186 patients with normal T4 and/or free T4 and normal T3 and/or free T3 but subnormal TSH (< 0.1 mU/l) levels in serum, 150 were under treatment with antithyroid drugs for hyperthyroid Graves' disease or with thyroid hormones for hypothyroidism. Twelve were in remission after treatment for Graves' disease, and 4 had destructive thyroiditis. Of the remaining 20 patients, 4 had autonomously functioning thyroid nodule (AFTN), 9 had euthyroid ophthalmic Graves' disease (EOG), and 7 had diffuse goiter without apparent ophthalmopathy (DG). When thyroid stimulating antibodies (TSAb) were measured in the last 3 groups of the patients, they were detected in none with AFTN but in all patients with EOG and DG. These 7 DG patients without ophthalmopathy had a clinical feature showing unstable thyroid functions, changeable to euthyroidism, overt hyperthyroidism and even hypothyroidism during follow-up. In conclusion, TSAb measurement is useful for detection of subclinical Graves' disease in euthyroid subjects with subnormal TSH levels in serum.

Adult

Clearance of pentosidine, an advanced glycation end product, by different modalities of renal replacement therapy.

We recently demonstrated that pentosidine, an advanced glycation end product, accumulates markedly as albumin-linked form (Palb) and in free-form (Pfree) in the plasma of patients with end-stage renal failure. The present study was undertaken to examine the clearance of Palb and Pfree by different modalities of renal replacement therapy, that is, hemodialysis (HD), continuous ambulatory peritoneal dialysis (CAPD), and renal transplantation. HD cleared Pfree (9.4 +/- 4.3 nmol/kg/HD) but not Palb, by diffusion but not by membrane adsorption, whereas CAPD cleared both Palb (4.03 +/- 2.01 nmol/kg/day) and Pfree (2.43 +/- 1.24 nmol/kg/day). Plasma total pentosidine levels were significantly (P < 0.05) lower in CAPD (0.97 +/- 0.41 nmol/ml) than in HD (1.19 +/- 0.41 nmol/ml), as the result of a lower serum albumin level in the former patients. Indeed, Palb expressed per mg albumin was virtually identical in HD and CAPD. By contrast, Pfree was significantly lower in CAPD than in HD. Palb levels were significantly correlated with plasma Pfree levels in both HD and CAPD patients, but not in the CAPD dialysate. Pentosidine transport across the peritoneum occurs mainly by diffusion, both as Palb and Pfree. Interestingly, peritoneal Palb clearance (0.17 +/- 0.07 ml/min) significantly (P < 0.00001) exceeded albumin clearance (0.11 +/- 0.05 ml/min). Palb levels being significantly higher (P < 0.0005) in the peritoneal fluid (36.28 +/- 18.55 pmol/mg) than in the serum (27.12 +/- 11.71 pmol/mg), thus raises the possibility of a facilitated diffusion of Palb or an active transport mechanism for protein-linked pentosidine into the peritoneal cavity. After renal transplantation, plasma Pfree fell rapidly, remained barely detectable after one month, and returned to normal at six months. By contrast, Palb fell more slowly and remained significantly above normal at six months, but returned eventually to normal levels. These findings demonstrate that: (1) both HD and CAPD remove Pfree; (2) the peritoneal clearance of Palb, might contribute to the lower level of plasma pentosidine in CAPD than in HD patients; and (3) renal transplantation is the best therapeutic modality to normalize both Palb and Pfree levels.

Adult

Implication of an increased oxidative stress in the formation of advanced glycation end products in patients with end-stage renal failure.

Recent studies have demonstrated a marked increase in the level of advanced glycation end products (AGEs) in the plasma, skin and amyloid fibrils of hemodialysis (HD) patients. The presence of AGEs in (beta2m) forming amyloid fibrils has been established in a previous immunochemical study relying on a monoclonal anti-AGE antibody. In the present study, Western blot analysis and immunohistochemistry reveal that the epitope recognized by this antibody is N epsilon-(carboxymethyl)lysine (CML) and that CML is one of the AGE structures present in amyloid fibrils. Thus, two AGE structures, CML and pentosidine, are now recognized in dialysis-related amyloidosis. AGE accumulation in uremia is not accounted for by elevated glucose levels. Since CML and pentosidine formation are closely linked to oxidative processes, we tested the hypothesis that a high oxidative stress enhanced AGE formation in HD patients. We focused on ascorbic acid (AA) because AA is easily oxidized under oxidative stress and its oxidized form (oxiAA) is a source of CML and pentosidine. In vitro incubation of beta2m with AA under atmospheric oxygen resulted in: (1) the rapid appearance of characteristic physicochemical properties of AGEs (brown color, fluorescence, polymerization tendency); (2) the transformation of beta2m into AGE-modified beta2m recognized by a specific monoclonal antibody; and (3) the accelerated formation of CML in beta2m and beta2m-peptide, recognized by mass spectrometry. A similar in vitro incubation of human serum albumin disclosed a parallel production of pentosidine measured by high-performance liquid chromatographic assay. In HD patients, the degree of AA oxidation, assessed as the ratio of oxiAA to total ascorbate, was more than twice as high as that of normal subjects (0.87 +/- 0.16 vs. 0.35 +/- 0.11, P < 0.0001), suggesting the presence of an increased oxidative stress. Interestingly, plasma level of oxiAA was correlated with the plasma levels of protein linked (P < 0.01, r2 = 0.25) and free (P < 0.05, r2 = 0.22) pentosidine. Altogether these results demonstrate that AGE, that is, CML and pentosidine, production is accelerated under oxidative stress, even in the absence of glucose. They suggest that, in uremia, CML and pentosidine production is determined both by an increased oxidative stress and the availability of precursors such as oxiAA. Finally, both CML and pentosidine contribute to the AGEs present in dialysis-related amyloid fibrils.

Amino Acid Sequence

Value of combined technetium-99m hydroxy methylene diphosphonate and thallium-201 imaging in detecting bone metastases from thyroid carcinoma.

Detectability of bone metastases from differentiated thyroid carcinoma by technetium-99m hydroxymethylene diphosphonate ([99m]Tc-HMDP) bone scan is considered to be poor. Thallium-201 (201Tl) is also widely used for detecting metastatic lesions. Our present study was aimed at the evaluation of the combined use of (99m)Tc-HMDP and 201Tl imaging in successful detection of bone metastases from differentiated thyroid carcinoma. Twenty-seven thyroidectomized thyroid cancer patients (19 females, 8 males; 12 papillary type, 15 follicular type) with 77 bone lesions were included in this retrospective study. All of these patients received ablative doses of radioiodine. Thyroidal origin of the lesions was proved by positive iodine-131 (131I) uptake. In 131I-negative lesions, histological proof or absence of tumor markers other than thyroglobulin was considered when computed tomography (CT) and/or magnetic resonance imaging (MRI) suggested metastatic nature of the lesions. Of the 77 lesions, 58 (75.3%) were positive and 19 were negative in the (99m)Tc-HMDP bone scintigraphy, whereas 53 lesions (68.9%) could be detected by 201Tl scintigraphy. However, within the 19 (99m)Tc-HMDP-negative lesions, 14 showed abnormal accumulation of 201Tl, and within the 24 201Tl negative lesions, 19 were positive in (99m)Tc-HMDP scan. This resulted in a combined sensitivity of 93.5%. Our present study concludes that combined (99m)Tc-HMDP and 201Tl imaging is a sensitive and effective method for detecting bone metastases from thyroid carcinoma.

Adenocarcinoma, Follicular

Mild and moderate hypothermia provide better protection than a burst-suppression dose of thiopental against ischemic spinal cord injury in rabbits.

BACKGROUND: Controversy exists over the efficacy of different methods for protecting the spinal cord against experimental ischemic injury. Therefore, the authors compared the protective effects of thiopental with those of hypothermia (35 degrees C and 32 degrees C) on hindlimb motor functions and histopathology after transient spinal cord ischemia. METHODS: Twenty-seven New Zealand white rabbits were assigned to one of the four groups: a thiopental-normothermia group (burst-suppression dose of thiopental; esophageal temperature = 38 degrees C; n = 7), a halothane-mild hypothermia group (halothane, 1%; esophageal temperature = 35 degrees C; n = 7), a halothane-moderate hypothermia group (halothane, 1%; esophageal temperature = 32 degrees C; n = 6), and a halothane-normothermia group (halothane, 1%; esophageal temperature = 38 degrees C; n = 7). The animals were then subjected to 20 min of spinal cord ischemia produced by occlusion of the aorta distal to the origin of left renal artery. Hindlimb motor function was observed for 48 h after reperfusion. Histopathology of the lumbar spinal cord also was examined. RESULTS: All animals in the halothane-mild hypothermia and halothane-moderate hypothermia groups were neurologically normal 48 h after ischemia. There was no statistical difference in the final neurologic status and histopathology between the thiopental-normothermia and halothane-normothermia groups. However, the final neurologic status and histopathology in both groups were worse than in the halothane-mild hypothermia or halothane-moderate hypothermia groups. There was a strong correlation between the final neurologic status and the numbers of normal neurons in the anterior spinal cord. CONCLUSIONS: These results suggest that mild and moderate hypothermia protects against ischemic spinal cord injury in rabbits, and a burst-suppression dose of thiopental does not offer any advantage over halothane.

Anesthetics, Intravenous

Myosin light-chain phosphorylation controls insulin secretion at a proximal step in the secretory cascade.

The aim of this study was to investigate how insulin secretion is controlled by phosphorylation of the myosin light chain (MLC). Ca2+-evoked insulin release from pancreatic islets permeabilized with streptolysin O was inhibited by different monoclonal antibodies against myosin light-chain kinase (MLCK) to an extent parallel to their inhibition of purified MLCK. Anti-MLCK antibody also inhibited insulin release caused by the stable GTP analog guanosine 5'-O-(3-thiodiphosphate), even at a substimulatory concentration (0.1 microM) of Ca2+. Free Ca2+ increased MLC peptide phosphorylation by beta-cell extracts in vitro. In contrast to the phosphorylation by purified MLCK or by calmodulin (CaM) kinase II, the activity partially remained with the beta-cell under nonstimulatory Ca2+ (0.1 microM) conditions. The MLCK inhibitor ML-9 inhibited the activity in the beta-cell with both substimulatory and stimulatory Ca2+, whereas KN-62, an inhibitor of CaM kinase II, only exerted an influence in the latter case. ML-9 decreased intracellular granule movement in MIN6 cells under basal and acetylcholine-stimulated conditions. We propose that MLC phosphorylation may modulate translocation of secretory granules, resulting in enhanced insulin secretion.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine

Acute hepatic failure following transcatheter arterial embolization for the treatment of hepatocellular carcinoma.

We conducted a retrospective analysis to evaluate the risk factors associated with the occurrence of acute hepatic failure following transcatheter arterial embolization (TAE) for hepatocellular carcinoma. From 1984 to 1993 we performed a total of 623 embolization procedures in 369 patients with both hepatocellular carcinoma and chronic liver disease. Within 2 weeks after TAE, 13 patients (2.1%) experienced hepatic failure as characterized by a rapid increase in serum bilirubin levels and the development of hepatic encephalopathy of grade 2 or higher. These results indicated that the following are risk factors for acute hepatic failure after TAE: poor hepatic functional reserve; high-dose infusion of chemotherapeutic agents, and a history of multiple embolization procedures.

Acute Kidney Injury

Synthesis and characterization of radioiodinated (S)-5-iodonicotine: a new ligand for potential imaging of brain nicotinic cholinergic receptors by single photon emission computed tomography.

(S)-5-Iodonicotine (4a), an (S)-nicotine analog iodinated at the 5-position of the pyridine ring, was synthesized and evaluated as a potential radiopharmaceutical for investigating brain nicotine receptors by single photon emission computerized tomography (SPECT). [125I]-(S)-Iodonicotine ([125I]-4a) was synthesized by the iododestannylation reaction under no-carrier-added conditions and purified by high-performance liquid chromatography (HPLC). The binding affinity of 4a for brain nicotine receptors was measured in terms of displacement of [3H]cytisine from binding sites in rat cortical membranes. The binding data revealed that the affinity of 4a was the same as that of (S)-nicotine and 80-fold higher than that of the (R)-enantiomer (4b). Biodistribution studies in mice disclosed that the brain uptake of [125I]-4a was rapid and profound. Regional cerebral distribution studies in rats by autoradiography disclosed that the accumulation of [125I]-4a was dense in the thalamus, intermediate in the cortex and striatum, and less marked in the cerebellum. Furthermore, the administration of (S)-nicotine reduced the uptake of [125I]-4a in the thalamus and resulted in a nearly identical level of radioactivity in the cerebellum. [125I]-(R)-5-Iodonicotine ([125I]-4b) showed more rapid washout from the brain and a less extensive regional cerebral distribution than the (S)-enantiomer ([125I]-4a). Thus, 4a bound to brain nicotine receptor in vivo, and therefore iodine-123-labeled 4a may be a potential radioligand for use in vivo cerebral nicotinic receptor studies by SPECT.

Animals

Assessment of thyroid growth stimulating activity of immunoglobulins from patients with autoimmune thyroid disease by cytokinesis arrest assay.

OBJECTIVE: To develop a novel bioassay for the assessment of thyroid cell growth stimulating activity using cytochalasin B (CB) and to test immunoglobulins (IgGs) from patients with autoimmune thyroid diseases. DESIGN: The assay is based on the principle that growing cells during incubation with CB show an increased number of nuclei in a cell (N/C index), since CB, at appropriate concentrations, is known to inhibit cytoplasmic cleavage without affecting nuclear mitosis. The N/C index represents potential DNA production while cells are incubated with CB. METHODS: FRTL-5 thyroid cells were incubated with various thyroid stimulators in TSH-free medium containing 2 mg/J CB for 3 days. After the incubation, the cells were harvested in trypsin/EDTA to obtain single cell suspension, fixed, dropped onto a glass slide, stained and observed under a microscope to determine the N/C index. RESULTS: Bovine TSH at 10(-3)-1.0 U/I, forskolin at 1x10(-7)-10(-5) mol/l, cholera toxin at 10x10(-5)-10(-3) mg/l, or (Bu)2cAMP at 1 x 10(-5)-10(-3) mol/l increased the N/C index up to approximately 2.0 in a dose-dependent manner. IgGs not only from 27 patients with untreated goitrous Graves' disease but also from 14 patients with goitrous Hashimoto's thyroiditis elicited an increase in the N/C index, which exceeded the mean + 2 S.D. of the values for 17 normal subjects (mean +/- S.D., 1.063 +/- 0.014). Four patients with primary myxedema displayed a normal N/C index. In Graves' disease, the N/C index did not correlate significantly with thyroid stimulating antibodies (TSAb) activities but did correlate significantly with estimated goiter size (P < 0.05). IgGs containing blocking-type TSH-receptor antibodies inhibited the TSH- or Graves IgG-stimulated increase in N/C index almost completely, but did not influence the stimulatory effect of IgG from two patients with Hashimoto's thyroiditis. CONCLUSIONS: We have developed a sensitive and simple assay for thyroid growth stimulating activity by using CB, and found that all tested patients with goitrous Graves' disease and goitrous Hashimoto's thyroiditis have thyroid growth stimulating immunoglobulins whose activity does not correlate with TSAb.

Animals

[Functional properties of receptors for glutamate and GABA in cultured trigeminal ganglion neurons].

Properties of receptors for glutamate, consisting of kainate, alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and N-methyl-D-aspartate (NMDA), and gamma-aminobutyric acid (GABA) in the rat trigeminal ganglion (TG) neurons were studied by means of the whole-cell patch-clamp technique. 1. All TG neurons (diameter 20 approximately 40 microns) responded to GABA, but none of them responded to AMPA, NMDA, and glycine. TG neurons responding to kainate were smaller than 25 microns and desensitized by prolonged agonist exposure. 2. On the basis of the dose-response curves, EC50 and Hill coefficient were found to be 13. 7 microM and 1.2 for kainate, while those for GABA were 28.6 microM and 2.0, respectively. 3. Most kainate receptors in the TG neurons showed linear current-voltage (I-V) relations, though some showed inward rectification. The "Instantaneous" I-V relationship for GABA was linear, where as the "steady-state" I-V relationship produced by ramp changes in potential showed outward rectification in some neurons. 4. The number of TG neurons responding to kainate increased until the 8th postnatal day, while all the recorded neurons responded to GABA in postnatal days. The results indicated that there are kainate and GABAA receptors in the TG neurons and suggested that they are composed of various subunits.

Animals

[Minimally invasive technique for mitral valve repair--the importance of intraoperative transesophageal echocardiography].

A 65-year-old male with mitral regurgitation was scheduled for the mitral valve repair by means of minimally invasive technique. The technique, which requires a 10-cm right parasternal incision, offers minimal discomfort, less postoperative pain, quick functional recovery and excellent cosmetic healing. However, the intraoperative monitoring by the transesophageal echocardiography was required to evaluate the mitral valve function and to confirm the complete removal of air from the apex of the left ventricle and right upper pulmonary vein due to the small operative field. In addition, the monitoring of the short-axis view of the left ventricle makes it possible to evaluate and to confirm the preload and the left ventricular contractility. We considered that the transesophageal echocardiography is essential and useful for the minimally invasive mitral valve repair.

Aged