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Biomedical subjects

Haruhiko Asano

Publications and source records attributed to Haruhiko Asano.

At least 19 recordsLinked to original sources
PubMed2007

The transcription factor KLF11 can induce gamma-globin gene expression in the setting of in vivo adult erythropoiesis.

Previous studies in a fetal erythroid cell line demonstrated that the transcription factor, Krüppel-like factor 11 (KLF11), could specifically induce transcription from a gamma-globin gene promoter, and that this induction was mediated through a specific canonical CACCC cis-DNA binding motif. We report here that ectopic expression of KLF11 can also induce fetal gamma-globin gene expression in the setting of adult erythropoiesis both in vitro and in vivo. Studies in an adult-stage murine erythroleukemia (MEL) cell line demonstrated that retrovirus vector-mediated transduction of KLF11 could increase both the amount of expression from a basally active, but not from a overtly silenced, recombinant gamma-globin transgene, as well as the frequency of cells expressing this transgene. A similar pattern of gamma-globin gene induction was also observed both in vitro and in vivo following KLF11 transduction of bone marrow from mice containing a basally active gamma-globin transgene. These studies provide the first evidence that ectopic expression of a transcription factor can induce gamma-globin gene expression in vivo during adult erythropoiesis.

Animals↗
PubMed2006

Importance of luxury flow for critically ill patients receiving a left ventricular assist system.

The presence of a significant organ dysfunction does not immediately exclude patients from consideration for treatment with a left ventricular assist system (LVAS). However, in treating morbid circulatory shock patients with multiple organ failure, it is important to know the preoperative and postoperative factor or factors related to the recovery of the damaged organ function. In this study, we retrospectively analyzed patients receiving a LVAS at our institution and tried to determine the important factors related to the survival of patients with multisystem failure. Twenty-seven patients who underwent LVAS placement at Saitama Medical School Hospital between 1993 and 2003 were included in this study. The preoperative risk factors analyzed were renal dysfunction, respiratory dysfunction, hepatic dysfunction, the existence of active infection, and the combination of all four factors. As a postoperative factor, the pump flow index (mean LVAS pump flow during the first 2 weeks after LVAS surgery divided by the body surface area) was analyzed. None of the analyzed preoperative factors could predict survival after LVAS surgery, but a pump flow index of less than 2.5 l/min/m2 had a significant relationship with death after LVAS surgery. Further analysis revealed that all the patients with a pump flow index of 3.0 l/min/m2 or more could overcome preoperative organ dysfunction. Congestive heart failure patients with multisystem failure need luxury pump flow for successful LVAS surgery; this factor could be especially important in device selection and postoperative management.

Cardiac Output↗
PubMed2006

Cardiac rest and reserve function in patients with Fontan circulation.

OBJECTIVES: In the present study, we systematically tested cardiac rest and reserve function in patients with Fontan physiology to check for inherent limitations of this circulation. BACKGROUND: Details of the mechanisms of cardiac performance that could account for adverse outcome after Fontan surgery are not well understood. METHODS: The subjects were 17 Fontan patients with good functional status (Fontan group) and 20 patients with normal two-ventricle circulation (control group). We examined baseline ventricular contractility, diastolic function, and loading factors, and examined changes in those parameters in response to increased heart rate (HR) due to atrial pacing and in response to beta-adrenergic stimulation, using ventricular pressure-area relationships during preload reduction. RESULTS: At baseline, the Fontan patients exhibited minimal abnormality of cardiac properties, but the significant increase in afterload resulted in decreased cardiac index. In addition, Fontan circulation was associated with limited inotropic response and worsening of diastolic filling with increased HR, leading to decreased systolic pressure and elevation of central venous pressure at higher HRs (p < 0.05 vs. control). Furthermore, beta-adrenergic reserve was markedly decreased in the Fontan group, compared with controls, owing to limited preload reserve rather than limited contractile reserve. CONCLUSIONS: Because normal ventricular-vascular interaction and augmentation of cardiac performance during increased HR and adrenergic stimulation are important for maintaining cardiac output and exercise capacity, the present results may have important implications for the mechanisms underlying adverse outcome after Fontan surgery. Thus, improvement of long-term prognosis of patients after Fontan surgery requires the development of medical interventions that can overcome such limitations inherent in Fontan circulation.

Child↗
PubMed2006

Loss of O6-methylguanine-DNA methyltransferase protein expression is a favorable prognostic marker in diffuse large B-cell lymphoma.

Although aberrant promoter hypermethylation of O6-methylguanine-DNA methyltransferase (MGMT) is a favorable prognostic marker in patients with diffuse large B-cell lymphoma (DLBCL), MGMT protein expression has not been thoroughly examined. The aim of this study was to evaluate the clinical implication of MGMT protein expression and its correlation with promoter hypermethylation of the gene. We investigated MGMT protein expression by immunohistochemical analysis of 63 DLBCL patients who received cyclophosphamide as part of multidrug regimens. In addition, promoter methylation of the MGMT gene was analyzed by a methylation-specific polymerase chain reaction assay, and correlations with chemotherapeutic effect and prognosis were statistically evaluated. Immunohistochemical assay results for MGMT protein were negative in 30.2% of patients with newly diagnosed DLBCL. Immunostaining results were closely correlated with the methylation status of the promoter. Promoter DNA methylation of the gene was not detected in 34 (81.0%) of 42 tumor samples determined to be MGMT-positive DLBCL by immunostaining and was detected in 15 (88.2%) of 17 cases of MGMT-negative DLBCL. Overall survival (OS) and disease-free survival (DFS) rates were significantly higher in MGMT-negative patients than in MGMT-positive patients (5-year OS, 81.3% versus 56.6% [P = .0375]; 5-year DFS, 66.3% versus 39.9% [P = .0121]). The combined rate for complete response (CR) plus unconfirmed CR was significantly higher in MGMT-negative patients (15/19, 79.0%) than in MGMT-positive patients (25/44, 56.8%) (P = .0488). A multivariate analysis showed that absence of MGMT expression was an independent prognostic factor for OS (relative risk, 4.09; P = .0258). Lack of MGMT protein expression is associated with aberrant promoter DNA methylation and appears to be a useful marker for predicting the survival of DLBCL patients.

Adult↗
PubMed2006

[Successful salvage of a patient with cardiac arrest caused by multiple pulmonary emboli and lung abscesses due to infective endocarditis of the tricuspid valve: a case report].

A 28-year-old female developed infective endocarditis in the tricuspid valve and multiple lung abscesses due to septic pulmonary emboli early after intensive therapy for ulcerative colitis. The pathogen was methicillin-resistant Staphylococcus aureus. Usual antibiotic agents and linezolid were administered. Three weeks later, she fell into cardiopulmonary arrest due to further pulmonary emboli and required mechanical circulatory assist. Fatal brain damage was suggested at first. Two days later, she fully regained consciousness and underwent tricuspid valve replacement using mechanical valve and extirpation of septic pulmonary embolus. Mechanical circulatory assist was discontinued on the next day. After strenuous administration of linezolid and other drugs for 9 weeks, she was discharged from hospital on foot. We believe that early surgical intervention should be considered in patients with infective endocarditis in the right heart and subsequent septic pulmonary emboli. Linezolid was very useful in this patient.

Acetamides↗
PubMed2005

Transcriptional regulation of FKLF-2 (KLF13) gene in erythroid cells.

FKLF-2 (KLF13) was cloned from fetal globin-expressing tissues and has been shown to be abundantly expressed in erythroid cells. In this study we examined the transcriptional regulation of the KLF13 gene. A 5.5 kb 5' flanking region cloned from mouse erythroleukemia (MEL) cell genomic DNA showed that major cis regulatory activities exist in the 550 bp sequence to the unique transcription start site, and that the promoter is more active in K562 cells than in COS-7 cells. The promoter was trans-activated by co-expressed GATA-1 through the sequence containing two CCAAT motifs, suggesting that GATA-1 is involved in the abundant expression of KLF13 mRNA in the erythroid tissue. Dual action, i.e. activating effect in COS-7 and repressive effect in K562 cell, was observed on its own promoter, suggesting a feedback mechanism for the transcriptional control of the KLF13 gene in the erythroid environment. These findings provide an insight on the mechanism of inducible mRNA expression of the KLF13 gene in erythroid cells.

Animals↗
PubMed2005

Successful bridge to resynchronization therapy with a left ventricular assist system in a patient with idiopathic dilated cardiomyopathy.

Implantation of a left ventricular assist system (LVAS) in patients with idiopathic dilated cardiomyopathy (DCM) may improve cardiac function and allow explantation of the device. Generally, an ejection fraction of more than 40% is considered necessary for successful weaning from an LVAS, but less than 10% of DCM patients with an LVAS can achieve such a significant recovery of cardiac function. Cardiac resynchronization therapy, or atrial-synchronized biventricular pacing, has been found to treat congestive heart failure and ventricular dyssynchrony effectively. Here we report on a patient with an LVAS, in whom enough functional recovery could be obtained with resynchronization therapy for the device to be explanted successfully. A 32-year-old man was implanted with a Toyobo-NCVC paracorporeal LVAS to treat his intractable heart failure caused by idiopathic dilated cardiomyopathy. While on the LVAS for 8 months, his cardiac function recovered to some extent. The ejection fraction of his left ventricle (LVEF) improved from 9% to 41%. He chose explantation of the device rather than heart transplantation. Because he occasionally showed a wide QRS pattern on his ECG, epicardial biventricular pacing leads as well as a biventricular pacemaker were implanted on LVAS explantation surgery. An echocardiogram 2 weeks after explantation showed a marked difference in his LVEF by switching his biventricular pacing on and off (40% with biventricular pacing on and 29% with it off). Biventricular pacing may help recovery of cardiac function in selected LVAS patients and contribute to the increase in bridge to recovery cases.

Adult↗
PubMed2005

Usefulness of selective contrast echocardiography and selective scintigraphy for the evaluation of pulmonary arteriovenous fistula in a patient with systemic arterial supply to a normal lung.

To determine a surgical procedure for the correction of a systemic arterial supply to a normal lung, it is important to evaluate whether the patient has a pulmonary arteriovenous fistula. In this article, the authors report for the first time a patient in which selective contrast echocardiography and selective perfusion scintigraphy from an abnormal artery clearly demonstrated and quantified the pulmonary arteriovenous fistula. The authors believe that these methods are useful in determining the appropriate operative procedure for this condition.

Aorta, Thoracic↗
PubMed2005

Vasopressin in the treatment of vasodilatory shock in children.

BACKGROUND: Many recent studies suggest that vasopressin deficiency is an important cause of catecholamine-resistant hypotension with vasodilation in adults, but little is known about vasopressin deficiency in children. METHODS: To clarify the usefulness of vasopressin administration in pediatric cathecolamine-resistant hypotension with preserved ventricular contractility, urinary output and blood pressure response to vasopressin were retrospectively analyzed in 12 consecutive patients (15 instances) who were treated with vasopressin. The causes of vasodilation were central nervous system disturbance (n = 5), side-effect of drug (n = 5), and infection (n = 5). Plasma vasopressin concentration was measured six times before vasopressin administration and five times during vasopressin administration. RESULTS: Patients were divided into four groups according to their response to vasopressin administration. In group 1 (n = 5), urinary output increased to > 3 mL/kg per h within 3 h after vasopressin administration. In group 2 (n = 4), urinary output increased to > 3 mL/kg per h from 3 to 5 h after vasopressin administration. In group 3 (n = 4), urinary output did not increase to > 3 mL/kg per min within 5 h after vasopressin administration, but systolic blood pressure increased to > 120% of the level at the time of vasopressin administration. All remaining patients were classified into group 4 (n = 3). Plasma vasopressin concentration were low considering the markedly hypotensive state in all six instances. Plasma vasopressin concentration during vasopressin administration were significantly increased compared with before administration (P < 0.05). No apparent side-effects were observed in this series. CONCLUSION: Vasopressin deficiency may occur in catecholamine-resistant hypotension of pediatric patients due to various causes including central nervous system disturbance, drug induced hypotension and sepsis. Small doses of vasopressin administration seems to be very effective in such conditions by increasing blood pressure and urinary output.

Adolescent↗
PubMed2005

[Coronary artery bypass grafting in patients undergoing chronic hemodialysis: importance of wound healing and hypoproteinemia].

OBJECTIVES: Outcome of coronary artery bypass grafting (CABG) in patients undergoing chronic hemodialysis was studied. METHODS: Between January 1996 and August 2004, 49 consecutive hemodialysis patients [38 males and 11 females, mean age 60.0 years (range 47-74 years)] underwent CABG using cardiopulmonary bypass. Duration of hemodialysis was 5.2 years (range 1 month-21 years), and 32 patients were diabetics. Surgery was conducted on the emergency/urgency basis in 12 patients, and intraaortic balloon pumping was placed in 7. Left ventricular ejection fraction was 57.7 +/- 16.3% (range 27-84%). Nine patients underwent concomitant valve surgery. CABG was performed under hypothermic cardiopulmonary bypass and ventricular fibrillation except in one patient, and intraoperative hemodialysis was also performed. Continuous hemodiafiltration was used in the early period after surgery. RESULTS: Number of bypass grafts was 3.0 +/- 1.0 (range 1-6), and the unilateral internal thoracic artery was used in 29 patients. Operation time, cardiopulmonary bypass time, and aorta clamp time were 313 +/- 87, 145 +/- 63, and 49 +/- 43 min, respectively. Diffuse pericardial adhesion was present in five patients. Severely atheromatous ascending aorta precluded manipulation in seven patients. Although the 30-day mortality was 2.0% (one case), all in-hospital mortality over 9 months was 14.3% (seven cases). The morbid events were mediastinitis in seven cases, reexploration for hemorrhage in seven, pneumonia in two, abdominal complication in three, and stroke in one. Delayed onset mediastinitis was common. Risk factors for death were mediastinitis and serum albumin levels < 3.5 g/dl (both p < 0.05), both of which were wound healing-related factors. CONCLUSIONS: CABG in hemodialysis patients carries a high risk. Patients with hypoalbuminemia appear to require special consideration.

Aged↗
PubMed2005

[Active infective endocarditis remaining latent for six weeks after discontinuation of antibiotic therapy: a case report].

A 75-year-old man was treated for 4 weeks with penicillin administration for infective endocarditis in the mitral valve caused by Enterococcus faecalis. The infection recurred, so he received penicillin administration for a further 6 weeks. He remained afebrile and all laboratory examinations were within normal limits for 6 weeks after the antibiotic treatment was discontinued, but the vegetation remained large and highly mobile. Since the onset, possible embolic episodes had occurred three times. He underwent mitral valve repair with annuloplasty. Although the infection appeared to have healed by antibiotic therapy, resected tissue was strongly positive for Enterococcus faecalis. This case suggests that surgery should be aggressively considered if the vegetation does not shrink markedly.

Aged↗
PubMed2004

Molecular cloning and characterization of ZFF29: a protein containing a unique Cys2His2 zinc-finger motif.

We have cloned a gene, ZFF29 (zinc-finger protein of human fetal liver erythroid cells 29), from human fetal liver erythroid cells. Two types of mature mRNA were identified and designated ZFF29a and ZFF29b. In human genome the ZFF29 gene is on chromosome 9q, and the two forms are splice variants. There is a unique transcription start site, which predicts major mRNAs composed of 2485 bases for ZFF29a and 1801 bases for ZFF29b. The anticipated mRNAs were demonstrated in K562 cells, but not in any adult human tissues examined by Northern blotting. In the mouse, reverse transcription-PCR revealed that the ZFF29 mRNA is present in adult bone marrow and ovary at a higher level than in any other tissues examined. These findings suggest that ZFF29 proteins are expressed in embryonic/fetal erythroid tissues. The deduced polypeptide chains of ZFF29a and ZFF29b are composed of 306 and 350 amino acids respectively. A unique zinc-finger motif composed of two contiguous Cys(2)His(2)-type fingers is common to both forms of ZFF29. They are nuclear proteins and ZFF29b, but not ZFF29a, is an activator of erythroid gene promoters.

Alternative Splicing↗
PubMed2004

Involvement of ryanodine receptors in muscarinic receptor-mediated membrane current oscillation in urinary bladder smooth muscle.

The urinary bladder pressure during micturition consists of two components: an initial, phasic component and a subsequent, sustained component. To investigate the excitation mechanisms underlying the sustained pressure, we recorded from membranes of isolated detrusor cells from the pig, which can be used as a model for human micturition. Parasympathomimetic agents promptly evoke a large transient inward current, and subsequently during its continuous presence, oscillating inward currents of relatively small amplitudes are observed. The two types of inward current are considered to cause the phasic and sustained pressure rises, respectively. Ionic substitution and applications of channel blockers revealed that Ca(2+)-activated Cl(-) channels were responsible for the large transient and oscillating inward currents. Furthermore, the inclusion of guanosine 5'-O-(2-thiodiphosphate) in the patch pipette indicates that both inward currents involve G proteins. However, applications of heparin in the patch pipette and of xestospongin C in the bathing solution suggest a signaling pathway other than inositol 1,4,5-trisphosphate (IP(3)) operating in the inward current oscillations, unlike the initial transient inward current. This IP(3)-independent inward current oscillation system required both sustained Ca(2+) influx from the extracellular space and Ca(2+) release from the intracellular stores. These two requirements are presumably SKF-96365-sensitive cation channels and ryanodine receptors, respectively. Experiments with various Ca(2+) concentrations suggested that Ca(2+) influx from the extracellular space plays a major role in pacing the oscillatory rhythm. The fact that distinct mechanisms underlie the two types of inward current may help in development of clinical treatments of, for example, urinary incontinence and residual urine volume control.

Animals↗
PubMed2004

Lethal thrombus in the carotid artery during operation for acute aortic dissection with cerebral malperfusion.

A drowsy patient with acute type A aortic dissection and cerebral malperfusion required emergency operation. Because the right carotid artery was totally obstructed, cerebral perfusion was first restored by cannulating it and the left femoral artery before midline sternotomy. However, a long fresh thrombus was found flowing backward from the obstructed carotid artery. This thrombus was removed, and both arteries were connected through a Y-shaped extracorporeal circulation circuit to reperfuse the brain. During the subsequent aortic procedure, both arteries were used for arterial inflow. Such thrombi can cause grave postoperative neurologic dysfunction. Carotid artery cannulation is mandatory in such cases.

Acute Disease↗
PubMed2004

Successful treatment of ascending aortic graft infection after operation for acute aortic dissection with peripheral malperfusion.

Mediastinitis with infection of an ascending aortic graft is hard to heal and is a highly fatal complication. We had a patient in whom mediastinitis with infection of such a graft as well as an ascending aorta-femoral artery bypass graft developed after the initial operation for type A aortic dissection accompanied by peripheral malperfusion. We treated it successfully by inserting a stent into the true lumen of the thoracoabdominal aorta and using a cryopreserved homograft to replace the infected ascending aortic fabric graft.

Acute Disease↗
PubMed2004

Surgery for active, culture negative endocarditis.

Culture negative infective endocarditis (CNE) poses very difficult problems during treatment. In this study it was found that of 132 surgically treated patients with infective endocarditis, causative organism was not identified in 46 (34.8 %). Pre- and perioperative conditions and clinical results of these patients were evaluated. CNE remained very frequent even in these years, and it did not decrease with time. Antibiotic treatment prior to microbiological examinations was commonly observed (nearly 90% orally, and 70% intravenously). In average, it took more than 2 months to establish the diagnosis of CNE after the onset, and both aortic and mitral valves were affected frequently (19.0 %). New York Heart Association functional class IV was observed significantly more commonly (61.9%) than culture positive patients. Frequencies of prosthetic valve endocarditis (12.2%), periannular abscess (36.3%), and embolism (21.4%) were similar. Infection was fairly controllable before surgery in 43.9% of CNE patients and in-hospital mortality rate was 14.3%, both of which were comparable to those of all culture positive patients. However, recurrence rate was relatively higher (10.0%). The conditions and outcomes of CNE were comparable to Staphylococcal endocarditis in some aspects, and were relatively worse than overall culture positive endocarditis.

Adult↗
PubMed2004

[Aortic root replacement using an allograft for active infective endocarditis with periannular abscess: single center experience].

OBJECTIVES: Results of aortic root replacement using an allograft for active infective endocarditis in the aortic position and periannular abscess were studied. METHODS: Aortic root replacement using a cryopreserved aortic allograft was performed 13 times in 12 patients (9 men, 3 women, mean age 52.8 years) at Saitama Medical School. Allografts were obtained from the Tokyo University Tissue Bank. Infection affected the prosthetic valve in 6 patients and the native valve in 7. Causative organisms were Staphylococci in 7 patients, Streptococci in 2, and unknown in 4. New York Heart Association functional class was II in 2 patients, III in 3, and IV in 8. Six patients required inotropic support. Four were mechanically ventilated. Two were in a state of profound shock. Four had multiple organ failure. Surgery was conducted under hypothermic cardiopulmonary bypass and cardioplegic arrest. Allograft was sewn into place by monofilament continuous sutures. Carrel patch technique was used for coronary artery reconstruction. Five patients underwent concomitant procedures (replacement of the ascending aorta in 2 patients, coronary artery bypass grafting in 1, mitral valve repair in 1, pulmonary artery reconstruction in 1). RESULTS: Duration of surgery, cardiopulmonary bypass, and aortic clamping were 507 +/- 154, 307 +/- 111, and 189 +/- 49 min, respectively. Two patients required intraaortic balloon pumping, and one required percutaneous cardiopulmonary support. Two patients in a state of shock died(hospital mortality: 15.4%). Duration of mechanical ventilation was 2.9 +/- 3.7 days. Intensive care unit stay was 4.6 +/- 5.5 days, and hospital stay was 61 +/- 26 days. One patient died of cancer 18 months later. One patient required reoperation 11 months later. Including operative death cases, cumulative survival at 2 years was 66.5% and freedom from cardiac events was 72.7%. CONCLUSIONS: Aortic root replacement with an allograft yielded acceptable clinical results.

Abscess↗