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N Nakahara

Publications and source records attributed to N Nakahara.

At least 19 recordsLinked to original sources
PubMed2002

Process of apoptosis induced by TNF-alpha in murine fibroblast Ltk-cells: continuous observation with video enhanced contrast microscopy.

Apoptosis is originally defined by unique morphological changes of dying cells, and the biochemical hallmark associated with apoptosis is internucleosomal DNA fragmentation. However, few report has shown the precise time course of the apoptotic events. The present study was designed to try to clarify apoptotic processes using a video-enhanced contrast-differential interference contrast (VEC-DIC) microscopy. The morphological changes of murine fibroblast Ltk-cells treated with TNF-alpha were divided into four stages: (i) pre-apoptotic, (ii) cytoplasmic shrinkage, (iii) membrane blebbing, and (iv) ballooning. Almost of the cells underwent cytoplasmic shrinkage and membrane blebbing within 6 hours after TNF-alpha exposure, and at about 9 hours, they were in the ballooning stage. Based on these data, we investigated the relationship between morphological changes and other biochemical features. The earliest event was exposure of phosphatidyl-serine at the cytoplasmic membrane, which was already observed in the pre-apoptotic stage. Loss of mitochondrial membrane potential was observed in the cytoplasmic shrinkage stage. Caspase-8/-3 activities already started increasing in the pre-apoptotic stage, and reached their peak at 6 hours after TNF-alpha exposure. DNA fragmentation occurred in the late phase of the membrane blebbing.

Animals↗
PubMed2002

Quantitative assessment of right ventricular structural abnormalities by right ventricular polar mapping of single photon emission computed tomogram.

The identification of right ventricular (RV) abnormalities is clinically important in the evaluation of arrhythmogenic substrates in right ventricular-originated ventricular tachycardia (RVT). The purpose of this study was to determine the diagnostic benefit of quantitative analysis in RV single photon emission computed tomography (SPECT) imaging with (99m)Tc-tetrofosmin/sestamibi in patients with RVT. Thirty patients with RVT (15 with idiopathic RVT and 15 with arrhythmogenic right ventricular cardiomyopathy (ARVC)) were compared with 27 control subjects (including 11 with right bundle branch block) with regard to the semiquantitative RV uptake score in each of six segments and the quantitative RV extent score in polar coordinate map displays by SPECT imaging. The RV total score and RV extent score were compared with the RV global function. Perfusion abnormalities were more frequently detected (P = 0.0001) in the ARVC group (59/90, 65.6%) than in the idiopathic RVT group (4/90, 4.4%) or controls (1/162, 0.6%). The RV extent score in the ARVC group (53.0 +/- 24.8) was significantly higher than that in the idiopathic RVT group (8.4 +/- 10.1) or controls (1.2 +/- 4.9). The RV extent score correlated well with the regional RV perfusion score (P < 0.0001) and with the RV ejection fraction (P < 0.0001). Non-invasive RV perfusion mapping using a (99m)Tc-labelled tracer is useful for the quantitative evaluation of RV substrates in patients with ARVC.

Adolescent↗
PubMed2001

Combination of stereotactic radiosurgery and cytokine gene-transduced tumor cell vaccination: a new strategy against metastatic brain tumors.

OBJECT: To determine if the combination of radiosurgery and tumor cell vaccine would enhance the therapy of metastatic lesions of the central nervous system (CNS), the authors examined the antitumoral effects of radiosurgery and cytokine-transduced tumor cell vaccine. METHODS: Fifty-five rats underwent intracranial implantation of 5 x 10(3) MADB 106 cells. On Day 3 after tumor implantation, 34 rats were inoculated in the flank with nonirradiated MADB 106 cells that had been retrovirally transduced to express granulocyte-macrophage colony-stimulating factor or interleukin-4. Twenty-seven rats (17 animals that had received the vaccine and 10 that had not) underwent radiosurgery performed using a gamma knife at maximum doses of 32 Gy on Day 5. No animals in the untreated group or in the vaccine-alone groups survived longer than 21 days. Animals treated by ra diosurgery alone displayed prolonged survival in comparison with untreated animals (p < 0.0001), but only one of 10 animals survived longer than 55 days. In contrast, 14 of 17 animals that received the combination therapy of radiosurgery and vaccination survived longer than 55 days (p = 0.0003 compared with animals that underwent radiosurgery alone). On Day 55, the long-term survivors were challenged by parental MADB 106 cells, which were implanted in the contralateral hemisphere. All animals from the combination therapy groups survived longer than 50 days after this challenge, but the single survivor from the radiosurgery-alone group died of tumor growth in 27 days. CONCLUSIONS: The combination of radiosurgery and cytokine gene-transduced tumor cell vaccine markedly prolonged animal survival and protected animals from a subsequent challenge by parental tumor cells placed in the CNS. The data provided by this study indicate that this combination therapy represents a strategy that may have clinical applicability for single and/or multiple metastatic brain tumors.

Adenocarcinoma↗
PubMed2001

[Usefulness of right ventricular Doppler index for predicting outcome in patients with dilated cardiomyopathy].

OBJECTIVES: Left ventricular Doppler index (LVDI) is believed to be a useful echocardiographic index of systolic and diastolic ventricular function. However, the usefulness of right ventricular Doppler index (RVDI) remains uncertain, especially in dilated cardiomyopathy. The predictive value of RVDI for estimating long-term cardiac events, including cardiac death, was investigated. METHODS: Fifty-nine consecutive patients with dilated cardiomyopathy (41 males and 18 females, mean age 52 +/- 15 years) were enrolled in this follow-up study. RVDI and LVDI were calculated as follows: DI = (isovolumic contraction time + isovolumic relaxation time)/ejection time. RESULTS: During a follow-up period of 3.7 +/- 3.0 years, 27 (46%) of the patients exhibited cardiac events, including cardiac death (n = 9), heart failure (n = 16) and tachyarrhythmias (n = 2) requiring in-hospital treatment. Patients with these cardiac events had higher LVDI and RVDI at the initial follow-up examination, and RVDI had a significant linear correlation with LVDI (LVDI = 0.550 + 0.452 x RVDI, r = 0.530, p = 0.0001). The 6-year survival rate was significantly lower in patients with both LVDI > or = 0.78 and RVDI > or = 0.49 than in other patients (50% vs 75%, respectively, p = 0.009). Cox proportional hazards model analysis showed that RVDI > or = 0.49 was the independent predictor of cardiac events (p = 0.0153) and cardiac death (p = 0.0003). CONCLUSIONS: RVDI is clinically useful for estimating the outcome of patients with dilated cardiomyopathy.

Adult↗
PubMed2000

Hypoparathyroidism potentiates cardiovascular complications through disturbed calcium metabolism: possible risk of vitamin D(3) analog administration in dialysis patients with end-stage renal disease.

BACKGROUND/AIM: Progressive cardiovascular calcification in dialysis patients with end-stage renal disease (ESRD) is a serious complication; however, the precise mechanism remains uncertain. We tested whether metabolic calcium abnormalities and hypoparathyroidism might have a correlation with cardiovascular complications in ESRD patients. METHODS: A series of 48 ESRD patients with cardiovascular diseases and/or congestive heart failure, aged 36-82 (61 +/- 12) years, 23 male and 25 female, were enrolled in this study. Serum total calcium (Ca, mmol/l), inorganic phosphate (mmol/l), and intact parathyroid hormone (iPTH, pg/ml) levels were determined in all cases. RESULTS: Organic heart disease was confirmed in 28 patients (58.3%), including 15 with coronary artery disease: 8 with aortic aneurysm, 8 with stenotic valvular heart disease, 9 with excessive mitral annular calcification, 3 with dialysis cardiomyopathy, and 7 with obstructive arterial disease. Serum iPTH measurement revealed hypoparathyroidism (iPTH <60) in 20 of 48 (41.7%) and hyperthyroidism (iPTH >/=200) in 13 of 48 (27.1%) subjects. The 20 patients with low iPTH had a higher prevalence of valvular heart disease, a higher total Ca level corrected for serum albumin (2.70 +/- 0.30 in low iPTH vs. 2.47 +/- 0.30 in normal iPTH, 2.35 +/- 0.20 in high iPTH, p = 0.003) and a higher tendency of vitamin D(3) analog use (65% in low iPTH vs. 33% in normal iPTH and 46% in high iPTH, p = 0.078). Moreover, corrected serum Ca exhibited a negative logarithmic correlation with serum iPTH: corrected Ca = -0.284x log (iPTH) + 3.021 (r = 0.637, p = 0.0001). Multiple logistic regression analysis revealed diabetes and hypoparathyroidism (iPTH <60) as risk factors for cardiovascular complications in ESRD. CONCLUSION: These results suggest that hypercalcemia and hypoparathyroidism in conjunction with vitamin D(3) use might play an important role in cardiovascular complications of chronic dialysis patients.

Adult↗
PubMed2000

[Intracardiac floating thrombi in patients with acute pulmonary thromboembolism].

The mortality and morbidity associated with residual intracardiac floating thrombi in patients with acute pulmonary thromboembolism remain uncertain. Thirteen patients (2 men and 11 women, mean age 56 +/- 15 years) with pulmonary thromboembolism underwent echocardiography within 24 hours from onset of symptoms. Four patients (31%) had floating intracardiac thrombi in the right heart: 3 in the right atrium and one in the inferior vena cava. The time to evaluation by echocardiography was shorter than in the patients without thrombi. The thrombi disappeared shortly (3.2 +/- 2.4 hr) after thrombolysis without adverse effects in these patients. After thrombolysis, clinical symptoms improved and pressure gradient between the right ventricle and right atrium decreased significantly (p < 0.01) from baseline 47 +/- 6 to 26 +/- 5 mmHg. Major bleeding complications occurred in 3 (43%) of the patients who underwent thrombolysis. Right-side intracardiac floating thrombus was easily detectable by early echocardiography. Thrombolytic agents are likely to be effective in patients with intracardiac floating thrombi.

Acute Disease↗
PubMed1999

Long-term site-related differences in the progression and regression of the idiopathic mitral valve prolapse syndrome.

The natural history of uncomplicated mitral valve prolapse (MVP) is not clearly understood. To determine the site-related differences in regression and progression of MVP, 112 patients with idiopathic MVP were enrolled in this echocardiographic follow-up study. Cardiovascular complications, including dysarrhythmias (n = 3, 2.7%), overt congestive heart failure (n = 4, 3.6%), progression of mitral regurgitation over one grade (n = 28, 25.0%), newly confirmed chordal rupture (n = 1, 0.9%), and surgical repair (n = 2, 1.8%), were observed in these patients during a follow-up period of 1-13 years (mean, 4.0 +/- 2.8 years). Multivariate analysis and Kaplan-Meier analysis revealed that posterior leaflet prolapse and significant mitral regurgitation (grade >/=2) were considerable risks for cardiovascular complications. Regression of MVP was seen in 17 (18.7%) of the anterior prolapse patients; however, new prolapse was observed in 40 (35.7%) patients, mainly in posterior prolapse patients. These results suggest that site-related differences exist in uncomplicated MVP prognosis and that MVP in the posterior leaflet has a poor outcome compared to that in the anterior leaflet.

Adolescent↗
PubMed1999

Scintigraphic evidence for a specific long-chain fatty acid transporting system deficit and the genetic background in a patient with hypertrophic cardiomyopathy.

The mechanism of cardiac uptake of long-chain free fatty acids has not been fully determined. We encountered a hypertrophic cardiomyopathy patient who showed a lack of cardiac uptake of 2 different types of long-chain fatty acid analogues on the scintigraphic images. Flow cytometric analysis revealed no platelet or monocyte CD36 molecule expression (type I CD36 deficiency) and his CD36 gene showed homozygous mutation for 478C to T substitution, leading to an abnormal CD36 amino acid sequence. These findings strongly suggest that a specific transporting system rather than a simple diffusion is commonly involved in the cardiac uptake of long-chain free fatty acids in humans, and that the CD36 protein is the most likely candidate for the specific transporter and to explain scintigraphic defects on fatty acid imaging.

Adult↗
PubMed1998

Fast spin-echo MR of the articular cartilage in the osteoarthrotic knee. Correlation of MR and arthroscopic findings.

PURPOSE: The objective was to assess the efficacy of fast spin-echo (FSE) imaging in the detection of articular cartilage abnormality in osteoarthrosis of the knee. MATERIAL AND METHODS: We studied 356 articular surfaces in 73 knees that had been examined by both MR imaging and arthroscopy. The MR images were obtained with FSE imaging (TR/TE 4200/100) on a 0.5 T unit. The surface abnormalities of the articular cartilage that were detected by MR imaging were compared with the arthroscopic findings. RESULTS: The overall sensitivity and specificity of MR in detecting chondral abnormalities were 60.5% (158/261) and 93.7% (89/95) respectively. MR imaging was more sensitive to the higher grade lesions: 31.8% (34/107) in grade 1; 72.4% (71/98) in grade 2; 93.5% (43/46) in grade 3; and 100% (10/10) in grade 4. The MR and arthroscopic grades were the same in 46.9% (167/356), and differed by no more than 1 grade in 90.2% (321/356) and 2 grades in 99.2% (353/356). The correlation between arthroscopic and MR grading scores was highly significant with a correlation coefficient of 0.705 (p < 0.0001). CONCLUSION: FSE sequence was less sensitive to mild cartilage abnormality but useful in detecting moderate to severe abnormality and in evaluating the degree of articular cartilage abnormality.

Adult↗
PubMed1996

Gadolinium-enhanced MR imaging of the wrist in rheumatoid arthritis: value of fat suppression pulse sequences.

OBJECTIVE: To determine the usefulness of fat-suppressed gadolinium (Gd)-enhanced MR imaging of the wrist in patients with rheumatoid arthritis (RA). DESIGN AND PATIENTS: Fat-suppressed Gd-enhanced T1-weighted spin-echo (SE) images were obtained and compared with other standard techniques in 38 wrists of 27 patients (22-77 years) with RA. Scoring based on the degree of synovial enhancement of each joint was developed and the total scores (J-score) were correlated with radiographic stage, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and symptomatic change in the follow-up study. RESULTS: Synovial proliferations showed marked enhancement in all the wrists. In addition, contrast enhancement in the bone marrow and tenosynovium was seen in 36 and eight wrists respectively. Fat-suppressed Gd-enhanced T1-weighted images demonstrated these abnormalities better than other techniques. The J-scores correlated well with values of CRP (P = 0.0034), but not with radiographic stages and ESR. CONCLUSION: Fat-suppressed Gd-enhanced T1-weighted SE images can clearly demonstrate most of the essential lesions in RA including the proliferative synovium, bone erosion, bone marrow inflammatory change, and tenosynovitis. Scoring based on the extent of Gd-enhancement of synovium can be useful in the assessment of the inflammatory status.

Adult↗
PubMed1995

[Magnetic resonance imaging of sacral insufficiency fractures: characteristic features and differentiation from sacral metastasis].

Seven patients with sacral insufficiency fractures and seven patients with sacral metastasis were studied with MR imaging. The diagnoses were confirmed with other imaging modalities and clinical follow-up. The insufficiency fractures appeared as bands of abnormal signal: low signal intensity on T1-weighted images and slightly low to iso signal intensity on T2-weighted images. The lesions were delineated better on T1-weighted images than on T2-weighted images. The sacral alae were involved in all patients; five patients had bilateral lesions. The lesions that run across the sacral body were seen in three cases. Inclined coronal images were useful in demonstrating the pattern of distribution of the sacral insufficiency fractures. In three patients with follow-up MR studies, the lesions were markedly reduced or disappeared. The sacral metastatic tumors were of low signal in density on T1-weighted images and iso to high signal in density on T2-weighted images. The extent and distribution patterns of the lesions were various. It is possible to differentiate sacral insufficiency fractures from sacral metastases based on their distribution patterns on MRI. However, if the diagnosis is uncertain or if the symptoms persist or become worse, follow-up MR studies may be necessary.

Aged↗
PubMed1994

Atypical appearance of adrenal pseudocysts.

We report 2 cases of adrenal pseudocysts that resulted from hemorrhage into a normal adrenal gland and that showed atypical imaging features on computerized tomography and ultrasonography. The presence of a solid component within the mass and/or central calcification, which is unlike the typical features of adrenal pseudocyst, suggested a diagnosis of adrenal tumor. The solid component diminished on computerized tomography in 26 days in case 1 and in 16 days in case 2, which seemed to represent resolving hematoma. The atypical appearance of these adrenal pseudocysts, especially the changeable pattern of the solid component within the mass, should be kept in mind to ensure a correct preoperative diagnosis.

Adrenal Gland Diseases↗
PubMed1994

Relationship between cytosolic Ca2+ level and contractile tension in canine basilar artery of chronic vasospasm.

In order to study the role of the Ca2+/calmodulin/myosin light chain kinase system in the development of chronic vasospasm caused by subarachnoid hemorrhage, the cytosolic Ca2+ level ([Ca2+]i), measured with fura-2, a fluorescent Ca2+ indicator, and contractile tension were measured simultaneously, and their quantitative correlation was examined in basilar arterial tissue obtained from the canine "two-hemorrhage" model. Sixteen adult mongrel dogs were divided into two groups, control (n = 8) and vasospasm (n = 8), and were killed 7 days after the first experimental subarachnoid hemorrhage. In basilar arterial tissue loaded with fura-2, 1) [Ca2+]i in the resting condition was not significantly different between the two groups; 2) the increment in [Ca2+]i induced by 40 mmol/L K+ stimulation was significantly smaller in vasospastic tissue (P < 0.01); and 3) 40 mmol/L K(+)-induced tension development per cross-sectional area for a fixed increment in [Ca2+]i was significantly greater in vasospastic tissue (P < 0.01). In tissue not loaded with fura-2, active myogenic tone, which was tentatively represented by the ratio of tonus relaxed with 10(-4) mol/L papaverine to initial resting tone, was significantly greater in vasospastic tissue (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Lymphocytic adenohypophysitis: an immunohistochemical study.

Lymphocytic adenohypophysitis is a rare inflammatory disorder of the anterior pituitary gland. In some cases, there is evidence of concurrent autoimmune disease. We present the case of a 39-year-old woman who developed visual disturbance during the early postpartum period. Magnetic resonance imaging revealed an intrasellar mass with suprasellar extension. Study of the tumor tissue showed diffuse infiltration of the entire pituitary gland by lymphocytes and plasma cells. Immunohistochemical examination revealed that the majority of the infiltrating lymphocytes were T cells that might have modulated the immunoreaction to the anterior pituitary gland. We suggest that the disorder is related to cell-mediated immunity as well as humoral immunity.

Adult↗
PubMed1990

Central muscarinic activities of an M1-selective agonist: preferential effect on reversal of amnesia.

Effects of FKS-508 (AF102B; cis-2-methylspiro (1,3-oxathiolane-5,3')-quinuclidine), a novel M1-selective agonist, on central muscarinic responses in mice were examined in comparison with oxotremorine. FKS-508 was slightly less potent (6 times) in reversal of scopolamine-induced amnesia (passive avoidance failure), but far less potent (260 and 55 times) in producing hypothermia and tremor than oxotremorine. These results show that the selective M1 agonist FKS-508 differentiates highly between the central muscarinic effects.

Animals↗
PubMed1989

Beneficial effects of FKS-508 (AF102B), a selective M1 agonist, on the impaired working memory in AF64A-treated rats.

The effects of FKS-508 [AF102B; cis-2-methylspiro(1,3-oxathiolane-5,3')quinuclidine], a selective M1 muscarinic receptor agonist, were examined to predict the possible activity on memory disorders using a T-maze and radial-arm maze task in experimental amnesia models. The amnesia models were produced by bilateral intracerebroventricular injection of ethylcholine aziridinium ion (AF64A), a selective cholinotoxin, in rats. Repeated administrations of FKS-508 (5 mg/kg/day, i.p.) for 5 weeks significantly ameliorated impaired performance of AF64A-treated rats (AF64A-rats) in a delayed alternation task in the T-maze. Repeated administrations of FKS-508 (1 and 5 mg/kg/day, p.o.) for 5 weeks significantly ameliorated acquisition failures of AF64A-rats in a radial-arm maze task. Single administration of FKS-508 (1 and 5 mg/kg, p.o.) significantly reduced the incorrect choices of AF64A-rats in a radial-arm maze task with 6 hr-delay time. No abnormalities in general behaviors, such as loss of appetite and ataxia, were observed in rats treated with FKS-508 repeatedly during 5 weeks. Our present results showed that FKS-508 can ameliorate memory impairments in AF64A-rats with central cholinergic hypofunction without causing any behavioral abnormalities. FKS-508 may be considered as a candidate for the clinical examination of the cholinergic hypothesis of senile dementia of the Alzheimer type.

Animals↗
PubMed1989

Chondrosarcoma of the posterior fossa--case report.

The authors describe a case of well differentiated (grade I) chondrosarcoma in a 52-year-old male. The tumor originated in the posteromedial wall of the left petrous bone and extended into the posterior fossa and cervical spine. He showed impaired functions of the left VII to XII cranial nerves. Plain skull x-rays demonstrated erosion of the left petrous and occipital bones, with speckled calcifications. Computed tomography showed a huge mass of slightly high density with mushroom-like calcifications, which was poorly enhanced by contrast medium. Inversion recovery magnetic resonance imaging clearly defined the low-intensity lesion, while the long spin-echo image depicted the tumor as mixed-intensity. On electron microscopic examination, the tumor cells were rich in Golgi apparatus, endoplasmic reticulum, glycogen granules and mitochondria in the cytoplasm, and formed many vacuoles crossing the cell membrane. These vacuoles were suggested to play an important role in matrix formation. Thirty nine other reported cases of chondrosarcoma are reviewed, and the two reported posterior fossa chondrosarcomas are compared with that of ours.

Chondrosarcoma↗