Biomedical subjects
Publications and source records attributed to H Tsuboi.
This study evaluated the role of adrenomedullin in patients with vasospastic angina pectoris. Adrenomedullin may be involved in regulating a basal tone of the coronary artery in these patients.
OBJECTIVES: We sought to elucidate the long-term prognostic importance of angiographic no-reflow phenomenon after percutaneous transluminal coronary angioplasty (PTCA) for acute myocardial infarction (AMI). BACKGROUND: Angiographic no-reflow phenomenon, a reduced coronary antegrade flow (Thrombolysis in Myocardial Infarction [TIMI] flow grade < or =2) without mechanical obstruction after recanalization, predicts poor left ventricular (LV) functional recovery and survival in the early phase of AMI. We hypothesized that angiographic no-reflow phenomenon also predicts long-term clinical outcome. METHODS: We studied 120 consecutive patients with their first AMI treated by PTCA without flow-restricting lesions. The patients were classified as either no-reflow (n = 30) or reflow (TIMI-3) (n = 90) based on post-PTCA cineangiograms to follow up (5.8 +/- 1.2 years) for cardiac death and nonfatal events. RESULTS: Patients with no-reflow had congestive heart failure (p < 0.0001), malignant arrhythmia (p = 0.038), and cardiac death (p = 0.002) more often than did those with reflow. Kaplan-Meier curves showed lower cardiac survival and cardiac event-free survival (p < 0.0001) in patients with no-reflow than in those with reflow. Multivariate analyses disclosed that no-reflow phenomenon was an independent predictor of long-term cardiac death (relative risk [RR] 5.25, 95% confidence interval [CI] 1.85 to 14.9, p = 0.002) and cardiac events (RR 3.71, 95% CI 1.79 to 7.69, p = 0.0004). At follow-up, survivors with no-reflow had higher end-diastolic and end-systolic LV volume indices and plasma brain natriuretic peptide levels, and lower LV ejection fractions (p = 0.0002, p < 0.0001, p = 0.002, p < 0.0001, respectively) than did those with reflow, indicating that no-reflow may be involved in LV remodeling. CONCLUSIONS: Angiographic no-reflow phenomenon strongly predicts long-term cardiac complications after AMI; these complications are possibly associated with LV remodeling.
9Alpha-fluoromedroxyprogesterone acetate (FMPA) is a novel synthetic analog of medroxyprogesterone acetate (MPA), widely used as therapeutic agent for breast and endometrium cancers. FMPA showed almost the same binding affinities to the progesterone and glucocorticoid receptors as MPA. In the rabbit corneal assay, FMPA, MPA and fumagillin significantly inhibited the angiogenic response induced by rat mammary tumor at doses of 0. 1, 1 and 50 microg/pellet, respectively, so FMPA showed greater anti-angiogenic activity than MPA and fumagillin. In the mouse dorsal air sac method, FMPA inhibited the mouse sarcoma 180 cell-induced angiogenesis by oral administration at a dose of 200 mg/kg. FMPA inhibited the activity of plasminogen activator (PA) in bovine endothelial cells. These results suggest that FMPA may be useful for diseases associated with angiogenesis by oral administration.
It has been shown that bio-trace metal elements are related to many diseases and the aging process. For many years, carcinogen hexavalent chromium (VI) has been known to be toxic to animals, but its dynamic toxicological mechanism is not sufficiently elucidated. Bioinorganic chemistry in terms of metallokinetic analysis of beneficial or toxic metal ions and their complexes is an important investigation for understanding their biochemical and physiological roles. We have tried to examine the real-time behavior of paramagnetic metal ions and complexes in animals, in which electron spin resonance (ESR) was capable of measuring paramagnetic species in chemical and biological systems. On the basis of our previous results on stable nitroxide spin probes, we have developed the in vivo blood circulation monitoring-electron spin resonance (BCM-ESR) method to analyze time-dependent ESR signal changes due to paramagnetic metal ions and their complexes in real time. When K2Cr2O7 or Na2Cr2O7 in saline was intravenously administered to rats, two ESR signals due to pentavalent chromium(V) were detectable in the circulating blood of rats. Cr(V) detected in the blood was indicated to be in the CrO(O4) and CrO(S2O2) coordination modes after the study on model complexes. From the changes of ESR signal intensities due to Cr(V) in the blood, the metallokinetic parameters were obtained using the pharmacokinetic analysis and the curve-fitting methods. The obtained results are important for understanding carcinogen chromate in terms of the formation of Cr(V) in animals. In addition, we propose the BCM-ESR method, which is useful to analyze the disposition of paramagnetic metal species in the blood of living animals.
Coronary arteriovenous fistulas are rare, particularly in association with coronary aneurysms. Two rare cases of patients with coronary arteriovenous fistulas and giant aneurysmal formation are described. A right coronary fistula that drained into the superior vena cava was demonstrated in one patient. The remaining patient had a documented left coronary fistula that drained into a main pulmonary artery and had evidence of several plexal vessels that transversed through the pulmonary trunk and toward the pericardial reflex. Under cardiopulmonary bypass, the fistulas and plexal vessels were successfully ligated without any injury to the native coronary circulation.
T cells may play a role in the pathogenesis of alopecia areata (AA). We attempted to elucidate the linkage between infiltrating T cells and hair regrowth processes by grafting scalp skin from the affected region of patients with AA onto severe combined immune deficiency (SCID) nude mice. When the AA scalp was grafted into the mice, the grafts were accepted, and normal hair regrowth was observed. Before grafting, CD4+ and CD8+ T cells had infiltrated into the peribulb area. After grafting, the telogen hair shifted to anagen hair, and the CD4+ and CD8+ T cell infiltrates in the bulb area decreased in all cases. CD8+ T cells had almost disappeared from all portions of the follicles. It has been suggested that CD8+ T cells play a crucial role in the pathogenesis of AA. The absence of CD8+ T lymphocytes that responded to follicular autoantigens may induce hair regrowth in the grafted skin. In addition, the CD4+ human T cells that had infiltrated or still remained in the upper-middle portions including the bulge area accompanied the HLA-DR expression after grafting. Infiltrating or surviving T cell phenotypes and locations changed during the hair cycle in the grafts. These results indicate that the location of infiltrated T cells and their phenotypes may participate not only in hair loss but also in regrowth of hair in AA.
The DAX-1 (also known as AHC) gene encodes an unusual member of the nuclear hormone receptor superfamily. DAX-1 plays a critical role during gonadal and adrenal differentiation since mutations of the human DAX-1 gene cause X-linked adrenal hypoplasia congenita associated with hypogonadotropic hypogonadism. In recent studies, DAX-1 was reported to function as a transcriptional suppressor of Ad4BP/SF-1, a critical transcription factor in gonadal and adrenal differentiation. With respect to implication of Ad4BP/SF-1 in the transcriptional regulation of the DAX-1 gene, inconsistent findings have been previously reported. We investigated the upstream region of the mouse Dax-1 (also known as Ahch) gene and identified a novel Ad4/SF-1 site by transient transfection and electrophoretic mobility shift assays. In addition, immunohistochemical analyses with a specific antibody to Dax-1 indicated the presence of immunoreactive cells in steroidogenic tissues, pituitary gland, and hypothalamus. Although the distributions of Dax-1 and Ad4BP/SF-1 were very similar, they were not completely identical. The expression of Dax-1 was significantly impaired in knock-out mice of the Ftz-f1 gene, which encodes Ad4BP/ SF-1. Taken together, our findings indicate that Ad4BP/SF-1 controls the transcription of the Dax-1 gene.
The pharmacologic response of coronary artery bypass conduits is of great importance. This study was designed to clarify the response of blood flow between the internal thoracic artery (ITA) and the ileocecal artery (ICA) to inotropic agents. The responses of the ITA and ICA to epinephrine, dopamine, isoproterenol, and dobutamine were examined by collecting free-flowing blood from a canine model. There were no significant differences in the response to inotropic agents between the ITA and the ICA. Epinephrine and dopamine increased the graft flow, whereas isoproterenol and dobutamine decreased the graft flow percentages of the cardiac output. These results suggest that the flow response to inotropic agents is equivalent in canine ITA and ICA grafts.
Despite a prolonged repetitive aortic cross-clamp time of 411 min, a patient who suffered a left ventricular rupture after undergoing mitral valve replacement following mitral valvuloplasty and Maze procedure recovered without any permanent residual left ventricular dysfunction. During the aortic cross-clamping we used tepid blood cardioplegia for myocardial protection. This case report serves to demonstrate the potential of tepid blood cardioplegia as an effective method of myocardial protection.
Two hundred forty-seven consecutive patients who had prehospital cardiac arrest and were transferred to a municipal hospital were studied to elucidate the characteristics of these patients and to investigate factors for improving the survival rate among prehospital cardiac arrest patients. Detailed information on 130 patients with cardiac etiology was analyzed: 110 were confirmed dead in the emergency department (group A); 14 survived less than 1 week (group B); 6 survived longer than 1 week (group C). Only one patient received cardiopulmonary resuscitation (CPR) from a bystander, and none received electrical defibrillation before arriving at hospital because, at the time, emergency personnel were not allowed to perform advanced life support (ALS) in Japan. The three characteristics for better prognosis after prehospital cardiac arrest were found to be as follows: being witnessed on collapse, receiving prompt ALS, and ventricular fibrillation on arrival at hospital. The survival rate would have been higher if more lay people could have performed CPR and if emergency unit personnel had been allowed to perform ALS.
In order to examine the changes in coronary artery morphology following cardiac transplantation, the intimal and medial areas and vascular components were measured 30 and 60 days postoperatively in rats receiving both iso- (n = 5, each time) and allotransplantations (n = 7, each time). Although cyclosporine A was administered intramuscularly (10 mg/kg per day) for 20 days following transplantation, graft rejection progressed gradually in the allotransplanted group. There were no clear changes in the intimal or medial areas following transplantation in the isotransplanted group. The intimal area of the coronary arteries in the allograft group was significantly thicker 30 and 60 days following transplantation, while the medial area of the coronary arteries in this group was significantly thinner than that of the isotransplantation group at these same time points. In the thickened intimal areas in the allotransplantation group, only the density of smooth muscle cells was higher following transplantation. In the thinned medial areas in the allotransplantation group, the densities of the smooth muscle cells and collagen were less than those in the isotransplantation group. These changes suggest that following transplantation, smooth muscle cells proliferate in the intimal areas, while smooth muscle cells and collagen are degraded in the medial areas.
8-hydroxydeoxyguanosine (8-OHdG) is one of the products which are excreted in urine as a result of oxidative damage to DNA. We investigated the feasibility of using 8-OHdG in urine as an index for oxidative damage to DNA in atopic dermatitis (AD). Seventeen patients with long-standing AD and 17 healthy volunteers were enrolled in this study. The severity of AD was evaluated by SCORAD index. Eosinophils, total IgE and lactate dehydrogenase-5 in peripheral blood were measured as clinical parameters for AD. A newly developed enzyme-linked immunosorbent assay method was used to measure urine 8-OHdG. The AD patients showed significantly higher levels (P < 0.0001) of 8-OHdG in their urine than corresponding controls. Urine 8-OHdG levels showed as strong a positive correlation as other haematological parameters did using the SCORAD index. Thus, we conclude that the urine 8-OHdG levels can also serve as a biochemical index of tissue damage and can act as a useful tool in the clinical evaluation of AD.
To investigate the molecular mechanisms underlying transendothelial migration of tumor cells, an essential process for their hematogenous dissemination, we developed an in vitro model system that allows the separate monitoring of cell adhesion and transmigration processes. This system uses a human pre-B lymphoma cell line, Nalm-6, and a cultured mouse endothelial cell line, KOP2.16. Nalm-6 cells rapidly adhered to KOP2.16 and subsequently transmigrated underneath them. Using this model, we examined the effects on transendothelial migration, of various reagents which specifically interfere with the function of intracellular signal transduction molecules. Treatment of Nalm-6 cells with wortmannin (WMN), herbimycin A, pertussis toxin, or C3 exoenzyme of Clostridium botulinum, which specifically inhibit P13 kinase and/or myosin light chain kinase, herbimycin-sensitive tyrosine kinases, heterotrimeric G proteins, and the small G proteins, and the small G proteins rho/rac, respectively, reduced transmigration in a dose-dependent manner, Pretreatment of KOP2.16 endothelial cells with WMN also reduced transmigration in a dose-dependent manner. Binding of Nalm-6 binding to KOp2.16 was not affected, even when Nalm-6 or KOP2.16 cells were pretreated with these inhibitors, indicating that the reduction of transmigration was not due to a reduction of Nalm-6 to KOP2.16. These results also indicate that the signal transduction pathway(s) involved in transmigration can be dissociated from that of adhesion. Our results support the notion that endothelial cells are not a passive barrier in lymphoma extravasation, but that they assist lymphoma cell extravasation.
Recent surgical advances leading to good operative results have contributed to the trend to useminimally invasive approaches, even in cardiac surgery. Smaller incisions are clearly more cosmetically acceptable to patients. When using a minimally invasive approach, it is most important to maintain surgical quality without jeopardizing patients. A good operative visual field leads to good surgical results. In the parasternal approach, we use a retractor to harvest an internal thoracic artery in coronary artery bypass surgery. Retracting the sternum upward allows for a good surgical view and permits the use of an arch cannula rather than femoral cannulation. When reoperating for aortic valve repair, the j-sternotomy approach requires less adhesiolysis compared with the traditional full sternotomy. No special technique is necessary to perform aortic valve surgery using the j-sternotomy approach. However, meticulous attention must be paid to avoiding left ventricular air embolisms to prevent postoperative stroke or neurocognitive deficits, especially when utilizing a minimally invasive approach. Transesophageal echo is useful not only for monitoring cardiac function but also for monitoring the persence of air in the left ventricle and atrium. This paper compare as the degree of invasion of minimally invasive cardiac surgery and the traditional full sternotomy. No differences were found in the occurrence of systemic inflammatory response syndrome between patients undergoing minimally invasive cardiac surgery and the traditional technique. Therefore it is concluded that minimally invasive surgery for patients with aortic valve disease may become the standard approach in the near future.
Twenty-eight patients (16 M, 12 F, age 11 approximately 72 yr, mean 52.8 yr) underwent surgery for infective endocarditis. Of the 27 patients, 16 were in the active stage and 11 were in the inactive stage. In patients in the active stage, aortic valve replacement (AVR) was performed in 5, mitral valve replacement (MVR) in 7, AVR + MVR in 1, AVR + MVR + tricuspid valve plasty (TVP) in 1 and other procedures in 2. In patients in the inactive stage, AVR was performed in 3, MVR in 4, AVR + MVR in 2, and other procedures in 2. Causative organisms were detected in 56.3% of the patients in the active stage and 54.5% in the inactive stage. Also in patients in the active stage, infection was not prolonged. No deaths occurred among patients in the inactive stage but five patients (31%) died postoperatively; 4 of the five also died, for had severe heart failure before surgery, three died of multiple organ failure and one died of subarachnoid hemorrhage due to infective aneurysm. We recommend surgery for the treatment of infective endocarditis even in the active stage before emergence of heart failure.
The influence of cytokines on the inflammatory response in surgery has recently been the subject of investigations. We measured tumor necrotic factor-alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6), interleukin 8 (IL-8), and granulocyte elastase (GEL) in 26 patients undergoing elective cardiac operations using cardiopulmonary bypass (CPB), preoperatively, immediately after CPB, and on post-operative days (PODs) 1, 3, and 6. To evaluate the effect of these cytokines on pulmonary function, the patients were divided according to whether the oxygenation index (OI) on POD 1 was > 250 or < 250, into groups A and B, respectively. TNF-alpha and IL-1 beta were undetectable and there were no significant differences in the preoperative IL-6, IL-8, and GEL levels. However, immediately following CPB, the mean IL-6, IL-8 and GEL levels in both groups were significantly higher than the preoperative levels (P < 0.01). Moreover, all these levels were significantly higher in group B than in group A, at 162 +/- 150 pg/ml vs 64 +/- 53 pg/ml (P < 0.05) for IL-6; 53 +/- pg/ ml vs 22 +/- 20 pg/ml (P < 0.01) for IL-8; and 2477 +/- 1642 mg/ l vs 1397 +/- 774 mg/l (P < 0.01) for GEL. The IL-6 levels returned to the preoperative values in both groups on POD 1; however, the GEL levels remained significantly higher in group B than in group A postoperatively, at 616 +/- 326 mg/l vs 378 +/- 70 mg/l on POD 1, and at 292 +/- 70 mg/l vs 218 +/- 62 mg/ l on POD 3 (P < 0.05). Thus high levels of cytokines such as IL-6, IL-8, and GEL may be detrimental to respiratory function.
The successful implementation of a reoperative Bentall procedure with concomitant total aortic arch replacement after ascending aortic replacement for acute aortic dissection is infrequently reported. We performed a modified Bentall procedure with total replacement of the aortic arch in a patient suffering from worsening aortic regurgitation (AR) and residual dissection. Our strategy involved the button method for coronary reconstruction, selective cerebral perfusion, the use of a composite graft with four branches for aortic arch replacement, and the administration of high-dose aprotinin to decrease bleeding.
We describe herein a technique for patent ductus arteriosus (PDA) closure using a method of video-assisted thoracoscopic surgical (VATS) interruption derived from video-assisted endoscopic surgery. This technique of repair was performed on five patients with a mean age of 3 years and a mean weight of 13.7 kg during 1994 and 1995. Under general anesthesia, two 10-mm trocars and two or three 5-mm trocars were inserted through the left thoracic wall. A video camera and specially designed surgical tools including scissors, dissectors, and a clip applicator were then introduced. The ductus was dissected, and two titanium clips were applied to interrupt the ductus completely. Successful closure of the PDA by this video-assisted technique was achieved in all patients. The only complication which developed in one patient was hoarseness for 2 weeks postoperatively. The hospital stay ranged from 7 to 12 days and there were no serious complications or deaths. There results indicate that video-assisted thoracoscopic surgical interruption is a safe and effective technique for achieving closure of PDA.