False-negative blood pool scan in hepatic angiosarcoma.
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Aged↗
Biomedical subjects
M Harada
Publications and source records attributed to M Harada.
Endothelin-1 and cardiotrophin-1 induce brain natriuretic peptide gene expression by distinct transcriptional mechanisms.
Cardiotrophin-1 (CT-1) a novel IL-6-related cytokine, induces distinct hypertrophic responses to endothelin-1 (ET-1) on cultured neonatal rat cardiac myocytes. We found that ET-1 and CT-1 show a distinct pattern of gene induction of natriuretic peptides. Elucidation of the transcriptional mechanisms of brain natriuretic peptide (BNP) gene induction by. ET-1 or CT-1 will provide better information for our understanding of the molecular mechanisms of cardiac hypertrophy. In this study, reporter constructs containing the human BNP 5' flanking sequence were transfected into neonatal rat cardiac myocytes and the cells were stimulated with ET-1 or CT-1. A total of 1813 bp of the human BNP 5' flanking sequence conferred an ET-1 inducibility on the reporter gene. However, it did not confer CT-1 inducibility. These results show that distinct mechanisms are involved in BNP gene induction by ET-1 or CT-1, and (in this study) that the CT-1 responsive element is not located in the region examined.
Animals↗
Interaction of myocytes and nonmyocytes is necessary for mechanical stretch to induce ANP/BNP production in cardiocyte culture.
In cardiac hypertrophy or ventricular remodeling, enlargement of myocytes and interstitial or perivascular fibrosis are observed simultaneously, which suggests an interaction between cardiac myocytes and fibroblasts. In this study we examined the mechanism of cyclic mechanical stretch-induced myocytic hypertrophy, focusing on the interaction between myocytes and cardiac nonmyocytes, mostly fibroblasts. Ventricular myocytes (MCs) and cardiac nonmyocytes (NMCs) were separately extracted from neonatal rat ventricles by the discontinuous Percoll gradient method and primary cultures of cardiac cells were prepared. When MCs were co-cultured with NMCs, the size of MCs and the ANP/BNP secretion were significantly increased. This hypertrophic change of MCs in the co-culture was significantly suppressed by BQ-123, an endothelin-A (ETA) receptor antagonist. Cyclic stretch did not induce hypertrophic responses in MC culture. However, it further increased ANP/BNP production in MC-NMC co-culture (2.2-fold and 2.1-fold increases vs. non-stretch group after 48-h incubation). This increase in ANP/BNP production in the co-culture was significantly suppressed by CV-11974, an angiotensin II (Ang II) type 1 receptor antagonist. This study raises the possibility that NMCs regulate cardiocyte hypertrophy via secretion of endothelin-1 and that Ang II is involved in the interaction between MCs and NMCs during the course of hypertrophic response of cardiocytes to mechanical stretch.
Angiotensin II↗
Delayed posttraumatic middle cerebral artery vasospasm demonstrated by magnetic resonance angiography: case report.
OBJECTIVE AND IMPORTANCE: Magnetic resonance (MR) angiographic diagnosis is a noninvasive method having high sensitivity and specificity in the detection of various cerebrovascular disorders. This is the first report of MR angiographic detection of delayed posttraumatic middle cerebral artery vasospasm, the occurrence of which has been rarely described. CLINICAL PRESENTATION: A 42-year-old man sustained head trauma in a traffic accident, which caused a right subdural hematoma. Even though the hematoma was irrigated through one burr hole on Day 10, the patient subsequently developed left hemiparesis in association with dysarthria 4 days after surgery. MR angiography demonstrated decreased flow signal in the right M1 and M2 portions, suggestive of vasospasm. INTERVENTION: The patient underwent intravascular volume expansion/ hemodilution therapy for 3 days. CONCLUSION: After the therapy, the ischemic symptoms completely disappeared. Follow-up study confirmed resolution of the flow signal in the right middle cerebral artery. It is suggested that MR angiography is a useful noninvasive method in the evaluation of posttraumatic cerebrovascular disorders, which constitute important secondary insults in head trauma.
Adult↗
Improvement with disodium cromoglycate of neutrophil phagocytosis and respiratory burst activity in a patient with hyperimmunoglobulin E syndrome.
We report a case of hyperimmunoglobulin E syndrome (HIE) complicated by neutrophil deficiency which was successfully treated with oral administration of disodium cromoglycate. A 48-year-old Japanese man with HIE developed Streptococcus pneumoniae meningitis. Laboratory tests after the meningitis revealed persistent neutropenia (300-800/mm3) and defects of phagocytosis and bacterial killing by neutrophils. Administration of disodium cromoglycate was started, and neutrophil counts gradually increased to 1200-1600/mm3. The impaired neutrophil activities returned to normal. The patient improved clinically; during the 2-year treatment, he had only two brief episodes of the common cold. Disodium cromoglycate may have potential clinical use in the treatment of cases of HIE even with neutrophil deficiency.
Cromolyn Sodium↗
Clinical significance of interruption of therapy with allylestrenol in patients with benign prostatic hypertrophy.
BACKGROUND: A multicenter, clinical trial investigated the effects of an interruption of antiandrogen therapy on subjective and objective clinical parameters in patients with benign prostatic hypertrophy (BPH). METHODS: Patients were given antiandrogen therapy with allylestrenol (50 mg/day) for 16 weeks. The medication was then withheld and the patients were carefully monitored for an additional 16 weeks. There were 34 BPH patients ranging in age from 55 to 82 years (mean, 66.1 years). The efficacy of allylestrenol was evaluated by its effects on prostate volume, maximum urinary flow rate (MFR), and symptom scores at the end of 16 weeks of treatment and then again at 32 weeks (16 weeks after cessation of therapy). RESULTS: Allylestrenol was effective in the treatment of BPH, and was still effective 16 weeks after the cessation of medication. The prostate volume did not change after treatment cessation nor did the total symptom score, but the MFR reversed to the pretreatment level. Serum testosterone (1.95 ng/mL), dihydrotestosterone, and gonadotropin levels decreased on therapy, but were completely reversed by the end of this study. A prostate needle biopsy revealed that after 16 weeks without therapy, some glands showed regressive glandular changes, while some glands showed slight hyperplastic changes of the secretory epithelium. Eight per cent of patients complained of loss of libido during this study. CONCLUSIONS: Allylestrenol is an effective and safe medical treatment for patients with symptomatic BPH. Hormonal and histopathologic findings suggest that the prostate gland may regrow after discontinuation of medication.
Aged↗
Life-threatening hemorrhage in a patient with gastric cancer and acquired hemophilia.
We report a case of a patient with life-threatening hemorrhage caused by the presence of acquired factor VIII inhibitors after gastrectomy for signet-ring cell carcinoma of the stomach. Acquired factor VIII inhibitors should be taken into consideration as a cause of acquired bleeding tendency among patients with gastrointestinal malignancies especially when the coagulation tests are unusual.
Aged↗
Proton magnetic resonance spectroscopy of the brain in three cases of Rett syndrome: comparison with autism and normal controls.
Rett syndrome (RS) is a clinically defined disorder characterized by autistic behavior, and cognitive and motor skill loss early in life. We performed 1H-MRS of the brain in 3 cases of RS in comparison with in autism and controls. The older patient with RS demonstrated decreased N-acetylaspartate (NAA)/choline (Cho) and NAA/creatine (Cr) ratios when compared with the autism and control groups, whereas the younger patients did not demonstrate these decreased metabolite ratios. The Cho/Cr ratio did not differ among Rett syndrome, autism and controls. Since the clinical stage did not differ among the 3 cases of RS, it was suggested that NAA was decreased with increasing age and was not related with the clinical stage of RS. The NAA/Cho, NAA/Cr and Cho/Cr ratios did not differ between autism and controls. The present data suggest that there may be a secondary degenerative process of late onset in RS, which pathophysiologically differs from autism.
Adolescent↗
[Clinical study of itraconazole for systemic fungal infections complicated with hematological malignancies--multicenter cooperative study. West-Japan Systemic Fungal Infection Study Group].
Itraconazole, an oral antifungal agent, was evaluated for the clinical efficacy and safety in patients documented or suspected of systemic fungal infection (SFI) complicated with hematological malignancies. The data was also evaluated according to serological tests and fungal culture. Out of a total of 79 patients, the clinical efficacy of itraconazole was evaluated in 52 patients, comprising 4 patients with proven SFI, 33 with clinical SFI, and 15 with suspected SFI. The overall efficacy was 67.3% (35/52), in which 25.0% in the established SFI group (1/4), 78.8% in the clinical SFI group (26.33), and 53.3% in the suspected SFI (8/15). When assessed according to the severity of SFI, the effectiveness rates were 75.0% in the mild group (15/20), 76.2% in the moderate group (16/21), and 36.4% in the severe group (4/11), resulting in significantly higher rates in the mild and the moderate groups than in the severe group (p = 0.0479). Out of the 10 patients who were switched from the previous antifungals, 7 patients were judged as showing marked or good responses. All of these patients were switched from intravenous fluconazole therapy. With respect to the safety of itraconazole, among 79 patients eligible for safety evaluation, adverse events such as hepatic dysfunction, increase in GOT and/or GPT, nausea and vomiting, and chest pain were observed in 6 patients (7.6%), and itraconazole may have been associated with them. As a conclusion, itraconazole proved to be effective and safe on SFI developed in patients with various hematological malignancies.
Administration, Oral↗
Effect of reduced bronchial circulation on lung fluid flux after smoke inhalation in sheep.
We determined the effect of reduced bronchial blood flow on lung fluid flux through changes in lung lymph flow, lung wet weight-to-dry weight (wet/dry) ratios, and pulmonary microvascular reflection coefficient (sigma). In the first of two surgical procedures, Merino ewes (n = 21) were surgically prepared for chronic study. Five to seven days later, in a second operation, the bronchial artery of the injection group (n = 7) was ligated, and 4 ml of 70% ethanol were injected into the bronchial artery to cause sclerosis of the airway circulation. In the ligation group (n = 7), only the bronchial artery was ligated. In the sham group (n = 7), the bronchial artery was surgically exposed but left intact without ligation or ethanol injection. One day after these operations the animals received a tracheotomy and 48 breaths of cotton smoke. The value of sigma was determined at two points: 24 h before the second surgical procedure and 24 h after smoke inhalation. Lung lymph flow, blood-gas parameters, and hemodynamic data were measured every 4 h after injury. At the end of investigation, samples of lung were taken for determination of blood-free wet/dry ratio. In the sham group, inhalation injury induced a gradual increase in pulmonary vascular resistance and lung lymph flow, which was associated with deterioration of oxygenation. Reduction of the bronchial blood flow attenuated these pathophysiological changes, and the degree of this attenuation was greater in the injection group than in the ligation group. The value of sigma was significantly higher after smoke inhalation in the injection group compared with the sham group (0.77 +/- 0.04 vs. 0.61 +/- 0.03, means +/- SE) at 24 h. The mean wet/dry ratio value of the injection group animals was 30% less than that of the sham group. Our data show that the bronchial circulation contributes to edema formation in the lung occurring after acute lung injury with smoke inhalation.
Animals↗
Endothelial nitric oxide synthase gene is positively associated with essential hypertension.
Essential hypertension has a genetic basis. Accumulating evidence, including findings of elevation of arterial blood pressure in mice lacking the endothelial nitric oxide synthase (eNOS) gene, strongly suggests that alteration in NO metabolism is implicated in hypertension. There are, however, no reports indicating that polymorphism in the eNOS gene is associated with essential hypertension. We have identified a missense variant, Glu298Asp, in exon 7 of the eNOS gene and demonstrated that it is associated with both coronary spastic angina and myocardial infarction. To explore the genetic involvement of the eNOS gene in essential hypertension, we examined the possible association between essential hypertension and several polymorphisms including the Glu298Asp variant, variable number tandem repeats in intron 4 (eNOS4b/4a), and two polymorphisms in introns 18 and 23. We performed a large-scale study of genetic association using two independent populations from Kyoto (n=458; 240 normotensive versus 218 hypertensive subjects) and Kumamoto (n=421; 223 normotensive versus 187 hypertensive subjects), Japan. In both groups, a new coding variant, Glu298Asp, showed a strong association with essential hypertension (Kyoto: odds ratio, 2.3 [95% confidence interval, 1.4 to 3.9]; Kumamoto: odds ratio, 2.4 [95% confidence interval, 1.4 to 4.0]). The allele frequencies of 298Asp in hypertensive subjects were significantly higher than those in normotensive subjects in both groups (Kyoto: 0.103 versus 0.050, P<0.0017; Kumamoto: 0.120 versus 0.058, P<0.0013, respectively). No such disequilibrium between genotypes was significantly associated with any other polymorphisms we examined; the Glu298Asp variant was also not linked to any other polymorphisms. In conclusion, the Glu298Asp missense variant was significantly associated with essential hypertension, which suggests that it is a genetic susceptibility factor for essential hypertension.
Adult↗
Thieno[2,3-d]pyrimidine-3-acetic acids. A new class of nonpeptide endothelin receptor antagonists.
On the basis of structural information for the cyclic hexapeptide endothelin (ET) receptor antagonist, TAK-044, a series of thieno[2,3-d]pyrimidine-2,4-dione derivatives bearing a carboxyl group and aromatic rings that were important for receptor binding were designed, synthesized, and evaluated for ET receptor binding affinities and inhibitory activities against ET-induced vasoconstriction. Optimization of each substituent in the thieno[2,3-d]pyrimidine ring led to the discovery of a novel and potent nonpeptide ET receptor antagonist, 6-(4-methoxymethoxyphenyl)-5-methylsulfonylaminomethyl-1-(2- methylthiobenzyl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]p yrimidine-3- acetic acid (32 g), which binded to human ETA and ETB receptor subtypes with affinities (IC50) of 7.6 and 100 nM, respectively. Compound 32 g effectively antagonized ET-induced vasoconstriction and the inhibitory effect mediated by the ETB receptor was more potent than that of bosentan, while the inhibitory effect mediated by the ETA receptor was slightly less potent than that of bosentan.
Acetates↗
Relative usefulness of measures of heart rate variability and neuroendocrine activity as indicators of autonomic nervous abnormality in patients with left ventricular dysfunction.
The aim of the study was to assess the relationship between changes in heart rate variability (HRV) and parameters of neuroendocrine activation in patients with various levels of left ventricular dysfunction. Measurements of HRV, plasma norepinephrine (PNE), and plasma atrial natriuretic peptide (ANP) were performed in 17 age- and gender-matched control subjects (group C) and in 39 patients with ischemic heart disease or cardiomyopathy who were subdivided into 3 equal groups according to their left ventricular ejection fraction: group N (normal); group M (mildly impaired); and group S (severely impaired). Spectral analysis of HRV (from 10-min electrocardiograms) was analyzed by the method of coarse-graining spectral analysis. PNE and ANP were significantly elevated in group S only (p<0.05). Log low-frequency power and log total power for group M were significantly lower than for group N (p<0.05). Log high-frequency power was significantly lower for group M than for group C (p<0.05). Thus, assessment of changes in HRV, which were observed earlier in the progress of left ventricular dysfunction than changes in neuroendocrine factors, may be a useful non-invasive method for the early detection of autonomic abnormality in patients with left ventricular dysfunction.
Aged↗
Coronary-pulmonary artery fistulae depicted by multiplanar reconstruction using magnetic resonance imaging.
We compared the imaging capability of magnetic resonance angiography (MRA) with that of conventional coronary angiography in a patient with coronary-pulmonary fistulae. Using the latter procedure, it is difficult to measure abnormal tortuous blood vessels in one section. However, the course of blood vessels could be evaluated quite well by rearranging serial cross-sectional MRA images using multiplanar reconstruction (MPR). This procedure allowed us to determine the anatomic positional relationship of these vessels to the peripheral cardiac great vascular system. MPR may detect sites of influx and outflow of abnormal blood vessels.
Adult↗
Genetic variation of mitochondrial cytochrome b genes among the subspecies of koala, Phascolarctos cinereus.
A conserved DNA region among the subspecies of koala, of mitochondrial cytochrome b gene, was employed to analyze the genetic variation among 3 available subspecies of koala. This conserved sequence, 307 bp DNA, was sequenced using polymerase chain reaction and direct DNA sequencing technique. Substitutions in the nucleotide sequences were observed, with which koalas can be divided into 3 DNA haplotypes subspecies, but the molecular data provided inconsistency with current classification of the 3 subspecies of koala.
Amino Acid Sequence↗
Prognostic factors of small-cell lung cancer in Okayama Lung Cancer Study Group Trials.
In order to elucidate factors influencing the prognosis of small-cell lung cancer (SCLC), we reviewed the records of 253 patients with SCLC and evaluated 20 pretreatment prognostic factors by univariate analysis and Cox's multiple regression analysis. Recursive partitioning and amalgamation (RPA) was employed to identify subgroups with similar survival rates. Cox's multiple regression analysis identified five significant factors: extent of disease, number of metastatic sites, serum albumin, serum lactate dehydrogenase, and presence of weight loss. Among these, extent of disease was the most influential factor. RPA analysis revealed three subgroups predicting significantly different prognoses. The median survival time and 3-year survival rate were 18.4 months and 20.6%, respectively for the good-risk group (limited disease without weight loss), 13.5 months and 9.1%, respectively for the intermediate-risk group (limited disease with weight loss or extensive disease with less than two metastatic sites), and 9.2 months and 0%, respectively for the poor-risk group (extensive disease with two or more metastatic sites). These results will be useful for development of new staging system or subsequent stratification for randomized trials.
Aged↗
Allogeneic peripheral blood stem cell transplantation as an alternative to allogeneic bone marrow transplantation.
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Bone Marrow Transplantation↗
Allogeneic peripheral blood stem cell transplantation for the treatment of refractory follicular lymphoma.
A 38-year-old male with follicular lymphoma at clinical stage IV failed to achieve complete remission (CR), and developed leukemic change. After the patient was further treated with intensive chemotherapy for acute lymphoblastic leukemia, lymphoma cells in the peripheral blood and bone marrow disappeared, but the bulky mass persisted. Then, the patient received allogeneic peripheral blood stem cell transplantation (allo-PBSCT) from his human lymphocyte antigen (HL A)-identical brother following high-dose cyclophosphamide and 12 Gy total body irradiation, and the patient achieved CR with the disappearance of Bcl-2 rearrangement. The patient is now alive in continuous CR for more than 19 months after allo-PBSCT.
Adult↗