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Biomedical subjects

Y Shigematsu

Publications and source records attributed to Y Shigematsu.

At least 37 records · Page 2Linked to original sources

Renin-dependent cardiovascular functions and renin-independent blood-brain barrier functions revealed by renin-deficient mice.

Renin plays a key role in controlling blood pressure through its specific cleavage of angiotensinogen to generate angiotensin I (AI). Although possible existence of the other angiotensin forming enzymes has been discussed to date, its in vivo function remains to be elucidated. To address the contribution of renin, we generated renin knockout mice. Homozygous mutant mice show neither detectable levels of plasma renin activity nor plasma AI, lowered blood pressure 20-30 mm Hg less than normal, increased urine and drinking volume, and altered renal morphology as those observed in angiotensinogen-deficient mice. We recently found the decreased density in granular layer cells of hippocampus and the impaired blood-brain barrier function in angiotensinogen-deficient mice. Surprisingly, however, such brain phenotypes were not observed in renin-deficient mice. Our results demonstrate an indispensable role for renin in the circulating angiotensin generation and in the maintenance of blood pressure, but suggest a dispensable role for renin in the blood-brain barrier function.

Angiotensin I↗

Evaluation of syringomyelia with three-dimensional constructive interference in a steady state (CISS) sequence.

The purpose of this study was to evaluate a three-dimensional (3D) constructive interference in steady state (CISS) sequence in the assessment of syringomyelia. Eleven patients with syringomyelia were prospectively studied with magnetic resonance imaging. All patients underwent sagittal imaging with T1- and T2-weighted spin-echo (SE), and 3D-CISS sequences. The SE and 3D-CISS images, as well as multiplanar reconstruction (MPR) images of the 3D-CISS sequence, were analyzed with regard to image quality, degree of artifacts, visualization of the extent and internal structure of the syringomyelia, and contrast-to-noise ratio (CNR) of the fluid within the syringomyelia. Contrast between the spinal cord and cerebrospinal fluid (CSF), as well as delineation was significantly poorer for the T1-weighted SE sequence than for the 3D-CISS sequence (P < 0.01), while there was no significant difference between the T2-weighted SE sequence and the 3D-CISS sequence. Artifacts induced by CSF flow were significantly more for the T2-weighted SE sequence than for the 3D-CISS sequence (P < 0.01). Although the extent of syringomyelia was delineated equally among the three sequences in 9 of 11 patients, it was better for the 3D-CISS sequence than for the SE sequences in the remaining two. Septation and communication between the cavities were best detected by the 3D-CISS MPR images. The CNR of the 3D-CISS sequence was significantly higher than that of the SE sequence (P < 0.01). The 3D-CISS sequence demonstrates the extent and internal structures of syringomyelia better than conventional SE sequences and should be added to SE sequences in the evaluation of syringomyelia.

Adult↗

Three cases of spinal dural AVF: evaluation with first-pass, gadolinium-enhanced, three-dimensional MR angiography.

A first-pass, contrast-enhanced three-dimensional (3D) magnetic resonance (MR) angiography with short acquisition time was performed for three consecutive cases with suspected spinal arteriovenous fistula (AVF). This MR technique demonstrated the feeding arteries and draining veins of the spinal dural AVF, and was very useful for the definite diagnosis of the lesions as a disease with arteriovenous shunt. With this MR technique, we could localize the feeding artery and shunt before conventional angiography. J. Magn. Reson. Imaging 2000;12:949-952.

Aged↗

Molecular and clinical analysis of Japanese patients with 3-hydroxy-3-methylglutaryl CoA lyase (HL) deficiency.

Deficiency of mitochondrial 3-hydroxy-3-methylglutaryl CoA lyase (HL, EC4.1.3.4.) is an autosomal recessive genetic disorder characterized by acute episodes of vomiting, hypotonia, and lethargy in the neonatal period or in infancy. Except in Saudi Arabia, where HL deficiency is the most common organic acidemia, the disorder is quite rare with only 41 cases being reported in the English literature, and only five known cases among Japanese. In this study, we present the results of a molecular analysis of all five Japanese patients together with their clinical phenotypes. Five different mutations in the HL gene were identified: one large deletion, one nonsense mutation, one missense mutation, and two splice mutations. Except for G835A (E279K) with its relatively common occurrence among Japanese, these mutations were unique to each family. The results of expression studies with mutated HL cDNAs confirmed the pathogenicity of these mutations and supported the importance of previously identified functional domains of the HL molecule, i.e., the putative catalytic site or dimerization site. In addition, we identified an alternative splicing event that resulted in the skipping of exons 5 and 6. This alternatively spliced product did not show HL activity and was present in various tissues of normal subjects. Clinically, all patients presented with similar symptoms, except that the timing of the initial presentation varied considerably, from 1 day to 1 year 3 months. In general, patients with null-activity mutations presented earlier in life, whereas those with residual activities presented later.

Age of Onset↗

Left ventricular mass and atrial volume determined by cine magnetic resonance imaging in essential hypertension.

To evaluate the relationship between left atrial volume determined by cine magnetic resonance imaging and progression of left ventricular hypertrophy (LVH), left atrial volume and echocardiographic left ventricular mass (LVM) were measured in 30 hypertensive patients (15 without LVH and 15 with LVH) and 10 normotensive control subjects. We also evaluated the effects of antihypertensive therapy on the cardiac chamber volumes and LVM in hypertensive patients. The cardiac chamber volumes and LVM were indexed by body surface area. Although there were no significant differences in left ventricular chamber volumes among the three groups, both maximum and minimum left atrial volume indexes, and the LVM index were greater in hypertensive patients with LVH than in the other two groups. The LVM index was correlated with maximum left atrial volume index (r = 0.74, P < .0001), and minimum left atrial volume index (r = 0.76, P < .0001), respectively. Furthermore, in multivariate models, the LVM index was significantly correlated with maximum left atrial volume index. In hypertensive patients with LVH, both maximum and minimum left atrial volume indexes, and the LVM index significantly reduced after treatment. The percent of changes in maximum left atrial volume index after treatment was significantly correlated with the percent of changes in LVM index after treatment. In conclusion, our data indicate that LVH is an independent determinant of left atrial enlargement, and both LVH and left atrial enlargement may be reversed by some effective therapeutic interventions.

Antihypertensive Agents↗

Accumulation of N-acetyl-L-aspartate in the brain of the tremor rat, a mutant exhibiting absence-like seizure and spongiform degeneration in the central nervous system.

The tremor rat is a mutant that exhibits absence-like seizure and spongiform degeneration in the CNS. By positional cloning, a genomic deletion was found within the critical region in which the aspartoacylase gene is located. Accordingly, no aspartoacylase expression was detected in any of the tissues examined, and abnormal accumulation of N-acetyl-L-aspartate (NAA) was shown in the mutant brain, in correlation with the severity of the vacuole formation. Therefore, the tremor rat may be regarded as a suitable animal model of human Canavan disease, characterized by spongy leukodystrophy that is caused by aspartoacylase deficiency. Interestingly, direct injection of NAA into normal rat cerebroventricle induced 4- to 10-Hz polyspikes or spikewave-like complexes in cortical and hippocampal EEG, concomitantly with behavior characterized by sudden immobility and staring. These results suggested that accumulated NAA in the CNS would induce neuroexcitation and neurodegeneration directly or indirectly.

Amidohydrolases↗

Dynamic MR imaging of neurohypophyseal germ cell tumors for differential diagnosis of infundibular diseases.

PURPOSE: To investigate the MR dynamic patterns of neurohypophyseal germ cell tumors (GCTs) for differential diagnosis of infundibular diseases affecting young people. MATERIAL AND METHODS: Eleven patients with neurohypophyseal GCTs underwent dynamic MR studies with Tl-weighted spin-echo (SE) or turbo SE techniques. Other infundibular lesions, including adenohypophysitis (n=3), Langerhans' cell histiocytosis (LCH, n=2), and 1 hemangioblastoma from von Hippel-Lindau disease, were also evaluated. Serial images were obtained every 15 s (turbo SE) or 30 s (SE technique) for 240 s after rapid injection of contrast medium. The dynamic patterns were analyzed quantitatively with the contrast medium enhancement ratio. RESULTS: On dynamic MR images, GCTs typically showed a gradual enhancement increase with a peak between 105 s and 180 s, while two showed a relatively rapid increase. LCH and hemangioblastoma showed a dynamic pattern similar to GCTs, while adenohypophysitis demonstrated a sharp rise and a steeper wash-out with an obvious peak before 90 s. CONCLUSION: Typical dynamic pattern of GCTs was the gradual enhancement increase without wash-out. Dynamic MR imaging can distinguish GCTs from adenohypophysitis, but is not useful for differentiation from LCH.

Adolescent↗

Identification of a response element for vitamin D3 and retinoic acid in the promoter region of the human fructose-1,6-bisphosphatase gene.

Fructose-1,6-bisphosphatase (FBPase) is a key gluconeogenic enzyme. The data herein show that both the enzyme activity and mRNA level of the human FBPase gene are enhanced by 9-cis retinoic acid (9cRA) and all-trans retinoic acid (atRA) as well as by 1,25-dihydroxyvitamin D3 (VD3) in human promyelocytic HL60 cells and normal monocytes in peripheral blood, which were used as an alternative source to liver for the DNA diagnosis of FBPase deficiency. To understand the molecular mechanism of this enhancing action, the 2.4 kb 5'-regulatory region of the human FBPase gene was isolated and sequenced. Using luciferase reporter gene assays, a 0.5 kb FBPase basal promoter fragment was found to confer induction by VD3, 9cRA, and atRA that was mediated by the vitamin D3 receptor (VDR), retinoid X receptor (RXR), and retinoic acid receptor (RAR). Within this region, a direct repeat sequence, 5'-TAACCTttcTGAACT-3' (-340 to -326), which functions as a common response element for VD3, 9cRA, and atRA, was identified. The results of electrophoretic mobility shift assays indicated that VDR-RXR and RAR-RXR heterodimers bind this response element. Collectively, these observations indicate that VD3 and RA are important modulators of the expression of the human FBPase gene in monocytic cells.

Blotting, Northern↗

Limbic lobe of the human brain: evaluation with turbo fluid-attenuated inversion-recovery MR imaging.

PURPOSE: To determine whether brain cortices have different signal intensities on turbo fluid-attenuated inversion-recovery (FLAIR) magnetic resonance (MR) images. MATERIALS AND METHODS: Coronal 5-mm-thick turbo FLAIR MR images in 56 neurologically normal patients (27 male and 29 female patients; age range, 12-73 years; mean age, 47 years) were evaluated retrospectively. Cortical signal intensities in the amygdala, hippocampus, cingulate gyrus, subcallosal area, insula, temporal lobe, parietal lobe, and occipital lobe were graded relative to cortical signal intensity in the frontal lobe. Contrast-to-noise ratios were compared for each cortical area. RESULTS: Increased signal intensity was frequently seen in the amygdala, hippocampus, cingulate gyrus, and subcallosal area, regardless of patient age. Signal intensities of temporal, parietal, and occipital cortices were similar to that of frontal cortex, and signal intensity of the insula was slightly higher than that of frontal cortex. There were no significant differences with respect to sex and laterality, whereas significant differences were found among cortical regions (P <.01). The contrast-to-noise ratios of the amygdala, hippocampus, cingulate gyrus, and subcallosal area were significantly greater than those of all other gray matter structures (P <.05). CONCLUSION: On turbo FLAIR images, high signal intensities of cortices of the limbic lobe are frequently seen in neurologically normal brain. These findings should not be considered abnormal.

Adolescent↗

Transient U wave inversion during treadmill exercise testing in patients with left anterior descending coronary artery disease.

The transient U wave inversion during exercise is specific for detecting left anterior descending coronary artery (LAD) disease. In a homogeneous patient group restricted to LAD disease, however, the significance of the electrocardiographic finding has not yet been clarified. Thus, clinical characteristics in patients with angiographically documented one-vessel disease of the LAD and exercise-induced U wave inversion were delineated. Symptom-limited treadmill exercise testing was performed in 60 patients (43 men, 17 women; mean age 64 +/- 8 years) with angina pectoris whose culprit lesion was located only in the LAD. U wave polarity and amplitude were determined before, during, and after exercise with the P-Q segment as the isoelectric line. Exercise-induced transient U wave inversion was defined as positive when there was a discrete negative deflection > or = 0.05 mV within the T-P segment. Of all patients, 16 (27%) had exercise-induced U wave inversion. There were no differences in age, male gender, antianginal medication use, and coronary angiographic data between the two patients groups: patients with and without U wave inversion. Heart rate and double product of heart rate and systemic systolic blood pressure at peak exercise were also similar. Prevalence of abnormal exercise-induced S-T segment shift was 94% (15 of 16 patients) and 61% (27 of 44 patients) of patients with and without U wave inversion, respectively. The difference was statistically significant (p = 0.02). Among patients with exercise-induced S-T segment shift, the proportion of patients with S-T segment elevation to all the patients was larger in patients with U wave inversion than in patients without U wave inversion [3 (20%) of 15 patients vs 0 (0%) of 27 patients, p = 0.03)]. In conclusion, the exercise-induced U wave inversion in patients with one-vessel disease of the LAD indicates the severe degree of myocardial ischemia induced in the territory perfused by the LAD. However, the electrocardiographic finding does not appear to have independent significance since it closely correlates with the presence of S-T segment shift.

Aged↗

A 25-year-old patient with low cardiac risk factors having a combination of variant angina and severe coronary arterial lesions--a case report.

A 25-year-old man with low cardiac risks underwent coronary arteriography because of chest pain at rest. His only risk factors for coronary artery disease was smoking. Both right and left coronary arteries were ectatic and the left anterior descending artery was obstructed. In the acetylcholine provocation test, the left circumflex coronary artery showed severe constriction. Thus, this patient was diagnosed as having a combination of variant angina and occlusive coronary artery disease.

Adult↗

Coronary spastic angina induced by anticholinesterase medication for myasthenia gravis--a case report.

Myasthenia gravis (MG) is characterized by weakness of skeletal muscles because of a decrease in the number of available acetylcholine receptors at neuromuscular junctions. Anticholinesterase medication is widely used to treat MG, but muscarinic side effects sometimes appear and limit the drug usage. To their knowledge, the authors present the first case of coronary spastic angina quite possibly induced by anticholinesterase medication to treat MG. The appearance of coronary spastic angina in the present case is likely mediated through the increase of acethylcholine by anticholinesterase medication.

Aged↗

Apical hypertrophic cardiomyopathy associated with life-threatening paroxysmal atrial flutter with a slow ventricular response: a case report.

A 58-year-old male patient had apical hypertrophic cardiomyopathy (HCM) associated with a life-threatening tachycardia due to atrial flutter. Following palpitation and dyspnea for 2-3 h, he became unconscious because of circulatory catastrophe, but was fully resuscitated. An electrocardiogram recorded just before the loss of consciousness revealed atrial flutter at a rate of 260 beats/min with a 2:1 ventricular response. He was diagnosed as having apical HCM based on the echocardiographic and left ventriculographic findings. Atrial stimulation at a rate of 150 pacings/min for 1 min caused a marked drop in systemic systolic blood pressure from 170 to 120 mmHg. The patient was treated with 150 mg of cibenzoline per day to prevent supraventricular tachyarrhythmias and to improve left ventricular diastolic function. At the time of the recent follow-up at 2 and a half years, he felt quite well.

Atrial Flutter↗

Effect of beta-blocker on left ventricular function and natriuretic peptides in patients with chronic heart failure treated with angiotensin-converting enzyme inhibitor.

To evaluate whether or not beta-blockers can improve the condition of patients with heart failure treated with a combination of diuretics, digitalis and angiotensin-converting enzyme inhibitor (ACEI), 52 patients with chronic heart failure who have been treated with ACEI for more than 6 months were enrolled. They were divided into 2 groups: 26 patients continued the same therapy another 6 months or more (group A), and 26 patients were given oral metoprolol for 6 months or more, in addition to the ACEI (group B). Echocardiographic parameters and atrial and brain natriuretic peptides (ANP, BNP) were measured. The left ventricular dimensions at end-diastole and end-systole were significantly decreased and fractional shortening was significantly increased in group B after 6 months' treatment with the beta-blocker, but these parameters remained unchanged in group A. Plasma levels of both ANP and BNP were significantly decreased in group B, but remained unchanged in group A. These results indicate that concomitant beta-blocker therapy can improve left ventricular function and attenuate plasma ANP and BNP levels in patients with chronic heart failure treated with ACEI.

Adrenergic beta-Antagonists↗

Time-course changes in left ventricular geometry and function during the development of hypertension in Dahl salt-sensitive rats.

Serial changes of left ventricular (LV) geometry and function during the development of hypertension were studied in 50 Dahl salt-resistant (DR) and 88 Dahl salt-sensitive (DS) rats fed an 8% NaCl diet beginning at the age of 6 weeks. Echocardiography at 6, 8, 11, 13, 14, 15, and 18 weeks and in vivo invasive hemodynamic determination at 6, 8, 11, 14, and 18 weeks were performed. After 11 weeks, 33 DS rats were observed for survival analysis. The survival analyses showed that the incidence of death was 57.6% due to heart failure, 27.3% due to stroke, and 15.2% due to sudden death. However, death in the early stages of hypertension was due almost entirely to sudden death or stroke. A high value of relative wall thickness (RWT) and a small end-diastolic dimension were predictive of sudden death and stroke, but LV mass (LVM) was not. Concerning the change in LV geometric patterns, LVM continued to increase to 18 weeks. The RWT increased or remained at a plateau up to 13 weeks, and then progressively decreased after 13 weeks. In contrast, LV function was hyperdynamic between 8 and 11 weeks when compared to DR rats. However, after 13 weeks, all hemodynamic variables of DS rats deteriorated progressively, and all DS rats died of heart failure. Thus, our study indicates that the cardiovascular events associated with the progression of hypertension vary widely according to the stage of hypertension and that RWT is more sensitive in predicting LV conditions than LVM in hypertension.

Animals↗

The effect of coronary vasospasm on the direction of ST-segment deviation in patients with both hypertrophic cardiomyopathy and vasospastic angina.

BACKGROUND: There has been no report of ECG changes during anginal attacks in patients with coexistent hypertrophic cardiomyopathy (HCM) and vasospastic angina. STUDY OBJECTIVES: To elucidate the change in ST-segment during anginal attacks in patients with coexistent HCM and vasospastic angina (the HCM group) in comparison with that of patients with vasospastic angina and no left ventricular hypertrophy (the non-HCM group). DESIGN: Retrospective study. PATIENTS: Twelve patients in the HCM group, and 28 patients in the non-HCM group. MEASUREMENTS: The direction of ST segment shift, either ST-segment elevation or depression, on the ECGs recorded during vasospastic anginal attacks with severe vasoconstriction in the epicardial coronary artery after intracoronary injection of acetylcholine. RESULTS: Age, male gender, and distribution of coronary arteries in which the vasospasm occurred were similar between the two groups. Collateral circulation to the affected arteries was absent in all the study patients. The prevalence of anginal attacks associated with ST-segment elevation was 2.7 times higher in the non-HCM group than in the HCM group (51. 5% [17 of 33 attacks] vs 18.8% [3 of 16 attacks], respectively; p = 0.03). CONCLUSIONS: In the HCM group, myocardial ischemia associated with a transmural injury pattern seen on the ECG, which is represented as ST-segment elevation, seldom develops during vasospastic anginal attacks because of marked left ventricular hypertrophy.

Acetylcholine↗

Evaluation of dural sinus invasion and extension of extra-axial intracranial tumors. The advantages of a high-resolution postcontrast 3-D gradient-echo technique.

OBJECTIVE: To assess the usefulness of a postcontrast 3-D Fourier transform (3DFT) gradient-echo (GRE) technique in dural sinus invasion and extension of extraaxial intracranial tumors in comparison with a conventional spin-echo (SE) technique. MATERIAL AND METHODS: Fourteen consecutive patients with 15 extra-axial tumors in contiguity with the dural sinus, including 14 meningiomas and 1 adenoid cystic carcinoma, underwent postcontrast T1-weighted SE and GRE MR studies. Detectability of dural sinus invasion and extension was evaluated using two sequences by two neuroradiologists in a blinded manner and compared with surgical results. Quantitative analysis was also performed to calculate the contrast-to-noise ratio (CNR) between lesion and dural sinus on SE and GRE images. The data were analyzed statistically using a matched paired t-test. RESULTS: In the qualitative evaluation, the detectability of dural sinus invasion in 3DFT-GRE images was superior to that using SE images. The mean CNR for all lesions was 3.86 on SE images and 5.63 on 3DFT-GRE images (p = 0.03). CONCLUSION: For evaluation of dural sinus invasion and the extension of extra-axial tumors, postcontrast 3DFT-GRE MR images were superior to conventional SE images.

Adult↗