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Biomedical subjects

Y Hirota

Publications and source records attributed to Y Hirota.

At least 73 records · Page 4Linked to original sources

Haloperidol prolongs diastolic phase of Ca(2+) transient in cardiac myocytes.

Haloperidol (HPL), a widely used antipsychotic drug, is known to induce serious ventricular arrhythmias. However, the mechanism underlying their induction is not clear. We therefore examined the effects of HPL on the intracellular Ca(2+) ([Ca(2+)](i)) transient and on cell motion in cultured cardiac myocytes, as well as the pathways involving the HPL-induced abnormality of Ca(2+) homeostasis. HPL prolonged the diastolic phase of the Ca(2+) transient, with a mid-diastolic re-elevation of [Ca(2+)](i). The re-elevation of [Ca(2+)](i) was shown to be provoked by Ca(2+) release from sarcoplasmic reticulum (SR), which can trigger delayed afterdepolarization, the major arrhythmogenic factor. The re-elevation of [Ca(2+)](i) coincided with cell re-contraction during diastole. The induction of this abnormality by HPL appears to be independent of the mechanisms of the antipsychotic action.

Animals↗

[Association between the results of blood test and blood PCB level of chronic Yusho patients twenty five years after the outbreak].

A cross-sectional study on the association between the results of blood test and the blood concentration of PCB was conducted on the chronic Yusho patients. The subjects were 265 Yusho patients (134 men and 131 women) who received the annual nationwide health examination for Yusho in 1993. The results of the blood test and questionnaire survey at the annual health examination were used for the analyses using ANCOVA. Serum levels of triglycerides, total cholesterol, GOT, GPT, gamma-GTP, total bilirubin, and conjugated bilirubin were associated with the blood concentration of PCB adjusting for sex, age, drinking habit, smoking habit and body mass index (BMI). Because the distribution of the serum levels was strongly skewed to the right except that of serum concentration of total cholesterol, they were log transformed to approximate to the Normal distribution. The association between age and the blood concentration of PCB was significant (P < 0.001), although the associations of sex, drinking habit, smoking habit and BMI to the blood concentration of PCB were not significant. With the adjustment for sex, age, drinking habit, smoking habit and BMI, the serum concentrations of triglycerides and total cholesterol were significantly associated with the blood PCB level expressed by loge (blood concentration of PCB in ppb-1) (P = 0.02 and P < 0.001, respectively). The associations of serum levels of GOT, GPT, gamma-GTP, total bilirubin and conjugated bilirubin to the PCB level were not significant. The results of this study suggests the need of careful observation on the serum lipids of Yusho patients, especially those with high concentration of blood PCB, because the serum concentrations of total cholesterol and triglycerides are prominent risk factors of heart diseases.

Adult↗

Cancer mortality of thorotrast patients in Japan: the second series updated 1998.

The 150 male patients exposed to Thorotrast who were confirmed by a 1975-1978 national survey with diagnostic X rays of 50,860 war-wounded soldiers were followed up between 1979 and 1998 (Aichi series or second series). Age-adjusted rate ratios of deaths from all causes were 3.0 times higher in Thorotrast patients compared to controls; this was statistically significant. Rate ratios for liver cancer, liver cirrhosis and leukemia were 35.0, 7.5 and 18.2, respectively.

Adult↗

Summary of entire Japanese thorotrast follow-up study: updated 1998.

Updated data from two series in a cancer mortality study for a total of 412 Japanese Thorotrast patients were combined. The rate ratio for all deaths of Thorotrast patients, compared to controls, started to increase after a latent period of 20 years after injection of Thorotrast. Rate ratios for liver cancer, liver cirrhosis, leukemia and lung cancer were 35.9, 6.9, 12.5 and 2.0 times higher, respectively, than those for controls.

Adult↗

[An early phase II study of autologous peripheral blood stem cell transplantation for acute myelogenous leukemia in first remission. Japan Blood Cell Transplantation Study Group].

We performed a multicenter, an early phase II clinical trial to evaluate the feasibility, safety and efficacy of myeloablative therapy supported by autologous peripheral blood stem cell transplantation (auto-PBSCT) for the treatment of acute myelogenous leukemia (AML) in first remission. A total of 105 patients were enrolled in the study, and 56 patients in first complete remission received auto-PBSCT. The median age was 44 years. Of the 56 patients, 34 (60.7%) had M2 or M3 AML by the French-American-British Classification system. The median concentration of infused CD34+ cells was 2.3 x 10(6)/kg by recipient body weight. Median days to reach an absolute neutrophil count > 500/microliter and a platelet count > 20000/microliter were 14 and 16, respectively. The median disease-free survival rate was estimated to be 62.0% at a median follow-up time of 534 days. Although the study enrolled a small number of patients and the follow-up period was relatively short, the preliminary results were encouraging and indicated that myeloablative chemotherapy with auto-PBSCT is feasible and can be performed safely as a post-remission therapy for AML. A prospective randomized clinical trial of auto-PBSCT versus standard chemotherapy alone will be necessary to assess the efficacy of high-dose therapy facilitated by auto-PBSCT as a post-remission therapy for AML.

Adolescent↗

Suppression of electrophoretic anomaly of bent DNA segments by the structural property that causes rapid migration.

Intrinsic DNA curvature is speculated to be a common feature of all satellite DNA sequences and may aid in the tight winding of DNA in constitutive heterochromatin. Several satellite DNAs, however, show unusually rapid migration in non-denaturing polyacrylamide gels, which is just the opposite behavior of that shown by curved DNA structures. Employing bovine satellite I DNA monomer, we attempted to understand the molecular mechanism of 'rapid migration'. The phenomenon of rapid migration was temperature-dependent and to a small extent polyacrylamide-concentration-dependent. Physiological or near-physiological concentrations of Mg2+and Ca2+ions bent the rapid migrating DNA segment. Predominance of purine-purine base stacking over purine-pyrimidine in nucleotide sequence was strongly indicated to be the cause of the rapid migration. Furthermore, they seemed to be implicated in the formation of induced DNA bend. We also found that the satellite I monomer contains an intrinsic DNA curvature as do many other satellites. Heretofore, the rapid migration property has concealed the presence of curvature.

Animals↗

Primary Non-Hodgkin's Lymphoma of the Breast: A Report of Two Cases.

BACKGROUND: Primary non-Hodgkin's lymphoma of the breast (PBNHL) is a rare neoplasm and PBNHL occuring in a man is extremely rare. METHODS: We report herein two cases of PBNHL and discuss methods of diagnosis and treatment. RESULTS: The first patient was a 35-year-old woman who presented with an elastic-hard mass in her left breast and adenopathy in her left axillary fossa. Mammography and ultrasonography suggested left breast cancer. Frozen sections demonstrated PBNHL histologically. Quadrantectomy of the breast was performed followed by chemotherapy. The second patient was a 65-year-old man with an elastic-hard mass in his left breast and left axillary lymphadenopathy. Mammography and ultrasonography suggested breast cancer or a soft tissue tumor. Intraoperative histological examination revealed a diagnosis of non-Hodgkin's lymphoma (NHL). A simple mastectomy and postoperative chemotherapy were performed and the patient had a good prognosis. CONCLUSION: A multidisciplinary approach including surgery, chemotherapy, andradiotherapy is indispensable in treating PBNHL, after diagnosis by excisional biopsy or aspiration cytology.

Journal Article↗

Synthesis and antitumor activity of ring A- and F-modified hexacyclic camptothecin analogues.

Nineteen ring A- and F-modified hexacyclic analogues of camptothecin were synthesized by Friedländer condensation of appropriately substituted bicyclic amino ketones with tricyclic ketone and were evaluated for cytotoxicity and topoisomerase I inhibitory activity. Seventeen of the compounds showed cytotoxic effects comparable or superior to those of 7-ethyl-10-hydroxycamptothecin (SN-38) against mouse leukemia P388 and human tumor cell lines HOC-21 and QG-56. Introduction of a compact and inductively electron-withdrawing substituent such as a hydroxy, methoxy, chloro, or fluoro group into position 5 of ring A of the hexacyclic compound remarkably increased the antitumor activity. The potency of topoisomerase I inhibition of these compounds showed good correlation with their cytotoxicity. Among them, the 4-methyl-5-fluoro hexacyclic compound was the most potent of all and was 10 times as active as SN-38 in in vitro antitumor activity.

Animals↗

Cloning and sequencing of cDNA encoding bovine macrophage colony-stimulating factor (bM-CSF) and expression of recombinant bM-CSF using baculovirus.

The cDNAs encoding bovine macrophage colony-stimulating factors alpha and beta (M-CSF alpha and M-CSF beta) were cloned and recombinant bovine M-CSF alpha (rbM-CSF beta) in its dimeric form was expressed by using a recombinant baculovirus/insect cell system. The predicted amino acid sequence of rbM-CSF alpha and rbM-CSF beta shared 83.3 and 75.9% (alpha), 75.3 and 65.9% (beta) similarity with the sequence for human and murine M-CSFs, respectively. The biological activity of rbM-CSF beta was confirmed by the colony-forming assay using mouse bone marrow cells. SDS-PAGE under a reducing condition showed that the molecular weight of rbM-CSF beta was approximately 34 kDa. On the other hand, Western blot analysis under a non-reducing condition revealed that this rbM-CSF beta was secreted in dimeric form into the cell supernatant.

Amino Acid Sequence↗

Influence of altered loading conditions on left atrial appendage function in vivo.

This study sought to examine the influence of heart failure treatment on left atrial (LA) appendage function in 10 patients with left ventricular dysfunction. After treatment of heart failure, LA appendage function markedly improved, less dependent on LA and left ventricular functions, which suggests that with altered loading conditions, LA appendage function changes chiefly through its intrinsic contractile property.

Aged↗

Collagen subtypes and matrix metalloproteinase in idiopathic restrictive cardiomyopathy.

BACKGROUND: Idiopathic restrictive cardiomyopathy is a rare disease characterized by diastolic dysfunction, and the pathogenesis of the stiff heart remains unclear. The purpose of this study was to analyze the subpopulation of collagen fibers and determine the expression of matrix metalloproteinase in restrictive cardiomyopathy. METHODS AND RESULTS: In endomyocardial biopsy specimens obtained from seven patients with restrictive cardiomyopathy, collagen fiber types I, III, and IV, and matrix metalloproteinase- and two were observed by light and electron microscopy, using monoclonal antibodies. Type I collagen was less prominent in the interstitium, whereas the immunoreactivity for type III collagen was marked. The immunoreactivity against matrix metalloproteinase-1 was observed along with types I and III collagen fibers and in the cytoplasm of some fibrocytes/fibroblasts. The matrix metalloproteinase-1 tended to increase when the reactivity against types I and III collagen was prominent. Both type IV collagen and matrix metalloproteinase-2 were observed along arterial walls and the basement membrane of cardiocytes. CONCLUSIONS: Increased type III collagen may play an important role as the cause of left ventricular stiffness in restrictive cardiomyopathy. The matrix metalloproteinase appeared to be involved in a cascade of collagen synthesis and the remodeling of the heart in patients with restrictive cardiomyopathy.

Adult↗

Circadian variation of myocardial ischemia in patients with unstable angina pectoris secondary to fixed and/or spastic coronary narrowing.

We investigated the circadian variation of myocardial ischemia in patients with unstable angina using a 24-hour 12-lead electrocardiographic monitoring system with computer analysis. The circadian variation of ischemic attacks in patients who had ST elevation showed a similarity to that of the onset of acute myocardial infarction and most of these patients had vasospasm without organic stenosis; no similarity was seen in patients with organic stenosis.

Aged↗

Assessment of left atrial appendage function after cardioversion of atrial fibrillation: relation to left atrial mechanical function.

Although several flow patterns in the left atrial appendage have been described, mechanical determinants of its function have not been elucidated in human beings. We attempted to investigate changes in left atrial appendage function after cardioversion of atrial fibrillation and examine the potential relation between appendage function and left atrial mechanical function. Twenty patients without mitral valvular disease underwent transesophageal and transthoracic echocardiography at 24 hours and 1 week after cardioversion of atrial fibrillation. Left atrial appendage function was assessed by the pulsed Doppler measurements of left atrial appendage emptying and filling velocities corresponding to early and late ventricular diastole, respectively. Left atrial mechanical function was evaluated by the transmitral A-wave velocity, percent atrial contribution of the total left ventricular filling (percent atrial filling), and the pulmonary venous A-wave velocity. Left ventricular function was also estimated with conventional M-mode echocardiography. The late appendage emptying and filling velocities markedly increased during 1 week after cardioversion (p < 0.0001, respectively). This finding was associated with an increase in left atrial mechanical function. Changes in the late emptying and filling velocities significantly correlated with changes in the transmitral A-wave velocity (r = 0.59, p < 0.01), percent atrial filling (r = 0.61, p < 0.005), and the pulmonary venous A-wave velocity (r = 0.56, p < 0.05). In contrast, little change was observed in the early emptying and filling velocities. There was no relation between the indexes of left ventricular function and those of appendage function. In conclusion, unless there was an alteration of the loading conditions, left atrial appendage function improved over several days after cardioversion, and its function was related to left atrial mechanical function.

Adult↗

Endoscopic sphincterotomy and laparoscopic cholecystectomy in an infant with cholecysto-choledocholithiasis.

Laparoscopic cholecystectomy (LC) and endoscopic sphincterotomy (EST) are widely accepted procedures for cholecysto-choledocholithiasis in adults. However, their use in infants has not been reported. An 8-month-old girl presented with high fever and obstructive jaundice. Ultrasound scan showed acute cholecystitis with stones in the bile duct. After 2-week-long antibiotic therapy the acute cholecystitis and hepatic impairment resolved. An endoscopic retrograde cholangiopancreatography (ERCP) confirmed choledocholithiasis and cholecystolithiasis. Risk factors for the development of biliary calculi were not detected. One month after the restoration of her liver function, she underwent EST using a side-viewing endoscope with a small sphincterotome. A common bile duct stone was extracted using a basket catheter. LC was then carried out. The time interval between the EST and LC was 34 days. No complications have been noted for 6 months.

Cholangiopancreatography, Endoscopic Retrograde↗

Reversible left atrial dysfunction possibly due to afterload mismatch in patients with left ventricular dysfunction.

Limited data are available concerning the influence of altered loading conditions on left atrial (LA) function. In addition, the underlying mechanism of the augmentation of atrial filling (A) velocity (assessed by transmitral Doppler measurement) after treatment of heart failure has been less studied. Therefore, we examined various indexes of LA function during the depression of left ventricular (LV) filling pressure resulting from treatment of heart failure. Twelve patients with LV dysfunction (ejection fraction < 50%) underwent right heart catheterization and transthoracic echocardiography before and after optimal treatment of heart failure. LV/LA volume and ejection fraction and mitral and pulmonary venous flow velocities were measured. LV stiffness (substitute for LA afterload) was assessed by the ratio of LV filling pressure to LV end-diastolic volume. After treatment of heart failure, the mitral A velocity significantly increased (38 +/- 9 to 58 +/- 16 cm/sec, p < 0.005) and there was a distinct attenuation of the difference of the pulmonary venous and mitral A-wave duration (43 +/- 29 to -8 +/- 31 msec, p < 0.005). These findings were associated with a marked decrease in LV stiffness (0.12 +/- 0.04 to 0.05 +/- 0.02 mm Hg/ml, p = 0.0001) and an increase in LA ejection fraction (27% +/- 7% to 38% +/- 8%, p < 0.005). There was a significant curvilinear relation between LA ejection fraction and LV stiffness (r = 0.63, p < 0.01). The mitral A velocity correlated positively with LA ejection fraction (r = 0.77, p < 0.0001) and inversely with LV stiffness (r = -0.52, p < 0.01). The reversible LA dysfunction suggests that the initial LA dysfunction is due to LA afterload mismatch rather than intrinsic LA disease, which also contributes to the augmentation of the mitral A velocity after heart failure treatment.

Atrial Function, Left↗

Ratio of pulmonary venous to mitral A velocity is a useful marker for predicting mean pulmonary capillary wedge pressure in patients with left ventricular systolic dysfunction.

In patients with an elevated left ventricular filling pressure, the mitral A wave is diminished while the pulmonary venous A wave is augmented because of decreased left ventricular compliance. We examined whether an increase in the ratio of pulmonary venous to mitral A velocity might be a marker for an elevated mean pulmonary capillary wedge pressure. Forty-one patients who had left ventricular systolic dysfunction underwent transthoracic Doppler echocardiography simultaneously or within 24 hours of right heart catheterization. There were 29 men and 12 women 61 +/- 12 (mean +/- SD) years of age. Underlying heart disease was ischemic cardiomyopathy in 27 and nonischemic cardiomyopathy in 14 patients. The same Doppler-hemodynamic study was performed on 8 patients after optimal management of heart failure. The ratio of pulmonary venous to mitral A velocity correlated strongly with mean pulmonary wedge pressure (r = 0.72, P < .0001). When the cutoff value of the ratio was set at 0.5 or higher, the sensitivity for predicting a pulmonary capillary wedge pressure of 15 mm Hg or more was 88%, and the specificity was 80%. The serial Doppler-hemodynamic study showed that the ratio decreased markedly after treatment of heart failure. The value was 0.84 +/- 0.29 before treatment and 0.36 +/- 0.17 after treatment (P = .001). An increased ratio of pulmonary venous to mitral A velocity is a useful marker for elevated pulmonary capillary wedge pressure among patients with left ventricular systolic dysfunction.

Aged↗