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Biomedical subjects

T Mano

Publications and source records attributed to T Mano.

At least 19 recordsLinked to original sources

Reversal of GATA-6 downregulation promotes smooth muscle differentiation and inhibits intimal hyperplasia in balloon-injured rat carotid artery.

The GATA-6 transcription factor is expressed in quiescent vascular smooth muscle cells (VSMCs) in culture, and levels of its transcript are rapidly downregulated on mitogen stimulation. In this study, we demonstrate that the GATA-6 transcript, protein, and DNA-binding activity are downregulated in rat carotid arteries on balloon injury. Downregulation was detected at 1 and 3 days after injury and recovered by 7 days. To assess the role of GATA-6 downregulation in injury-induced vascular lesion formation, adenoviral vectors were used to express wild-type human GATA-6 cDNA (Ad-GATA6) or an inactive mutant cDNA that lacks a portion of the zinc-finger domain (Ad-GATA6DeltaZF). Adenovirus-mediated GATA-6 gene transfer to the vessel wall after balloon injury partially restored the levels of GATA-6 protein and DNA-binding activity to before injury levels. The local delivery of Ad-GATA6 but not Ad-GATA6DeltaZF inhibited lesion formation by 46% relative to saline control and 50% relative to a control adenovirus that expressed lacZ. Local delivery of Ad-GATA6 also reversed changes in the expression patterns of smooth muscle myosin heavy chain, smooth muscle alpha-actin, calponin, vinculin, metavinculin, and proliferating cell nuclear antigen that are associated with injury-induced VSMC phenotypic modulation. These data indicate that the injury-induced downregulation of GATA-6 is an essential feature of VSMC phenotypic modulation that contributes to vessel lesion formation.

Adenoviridae

Mechanisms of fine-surface-texture discrimination in human tactile sensation.

The purpose of this study was to evaluate the ability of touch to discriminate fine-surface textures and to suggest possible mechanisms of the discriminations. Two experiments were performed. In experiment 1, aluminum-oxide abrasive papers were adopted as stimuli, and psychometric functions and difference thresholds were determined in fine-surface-texture discrimination tasks. The grit values of abrasive papers were 400, 600, 1200, 2000, 3000, 4000, and 8000; corresponding average particle sizes were 40, 30, 12, 9, 5, 3, and 1 micron, respectively. Ten subjects participated in experiment 1. The difference thresholds obtained in experiment 1 were between 2.4 and 3.3 microns. In experiment 2, the tasks were discriminations of ridge height. The cross sections of the etched ridges were rectangular and the ridge heights were 6.3, 7.0, 8.6, 10.8, 12.3, 18.5, and 25.0 microns. Six subjects participated in experiment 2. The difference thresholds in experiment 2 were between 0.95 and 2.0 microns. It was reasoned, based on the Weber fraction values calculated from the difference thresholds and on the limit of neural information-processing ability of humans, that the subjects discriminate fine roughness only from the amplitude information presented in surface unevenness.

Adult

Responses of sympathetic outflow to skin during caloric stimulation in humans.

We previously showed that caloric vestibular stimulation elicits increases in sympathetic outflow to muscle (MSNA) in humans. The present study was conducted to determine the effect of this stimulation on sympathetic outflow to skin (SSNA). The SSNA in the tibial and peroneal nerves and nystagmus was recorded in nine subjects when the external meatus was irrigated with 50 ml of cold (10 degrees C) or warm (44 degrees C) water. During nystagmus, the SSNA in tibial and peroneal nerves decreased to 50 +/- 4% (with baseline value set as 100%) and 61 +/- 4%, respectively. The degree of SSNA suppression in both nerves was proportional to the maximum slow-phase velocity of nystagmus. After nystagmus, the SSNA increased to 166 +/- 7 and 168 +/- 6%, respectively, and the degree of motion sickness symptoms was correlated with this SSNA increase. These results suggest that the SSNA response differs from the MSNA response during caloric vestibular stimulation and that the SSNA response elicited in the initial period of caloric vestibular stimulation is different from that observed during the period of motion sickness symptoms.

Adult

[Connatal type of Pelizaeus-Merzbacher disease: a case report].

Pelizaeus-Merzbacher disease (PMD) is a hereditary disorder with myelin dysplasia in the central nervous system. The connatal type is a more severe form compared to the classical type and shows developmental arrest or deterioration, nystagmus, spasticity, and/or convulsions in the neonatal period. A 1 1/4-year-old Japanese boy diagnosed as connatal type PMD is reported here. Soon after his birth, he demonstrated horizontal and rotatory nystagmus and opisthotonic posture. At the age of 10 months, he had difficulty in feeding. At the age of 1 year, he presented more severe opisthotonic posture and frequent vomiting. He showed deterioration in gross motor development. His chromosome analysis showed a normal male karyotype. Electroencephalogram did not show a sleep spindle. Auditory evoked brainstem responses (ABR) showed only wave I on both sides. Visual evoked potentials (VEP) showed prolongation of latencies. These results were compatible with PMD. Nuclear magnetic resonance imaging (MRI) demonstrated in the white matter of cerebrum and brainstem no high intensities on T1-weighted images and diffuse high intensities on T2-weighted images. Such absence of myelination including the brainstem was characteristic to the connatal type PMD. The diffuse disturbance of myelination appeared to correlate with the severity of clinical symptoms.

Brain

Attenuation of regional differentiation of sympathetic nerve activity during sleep in humans.

The purpose of the present study was to clarify how the regional differentiation of sympathetic nerve activity (SNA) is modified during natural sleep in humans. In humans, muscle and skin sympathetic nerve activities (MSNA, SSNA) have been reported to discharge independently according to a regional differentiation of SNA during wakefulness. However, in natural sleep, MSNA and SSNA have been documented to synchronize during sleep stage 2 (Rechtschaffen and Kales). In the present study, we measured MSNA and SSNA simultaneously using a double recording technique of microneurography in eight healthy volunteers during natural sleep, and analyzed how MSNA and SSNA can be synchronized. We found that the synchronicity of MSNA and SSNA was accelerated in correlation with the deepening of the non-rapid eye movement (nonREM) sleep stages. We also documented that the burst properties of MSNA different from those of SSNA in wakefulness become similar to those of SSNA in the sleep stage, and MSNA synchronizes with SSNA. The synchronicity of MSNA and SSNA is presumably caused by a reduced effect of central inhibitory baroreflex pathways on MSNA during nonREM sleep. The present findings suggest that the regional differentiation of sympathetic nerve activity is attenuated with the deepening of nonREM sleep stages.

Adult

Effects of thyroid hormone on the sorbitol pathway in streptozotocin-induced diabetic rats.

Sorbitol accumulation plays an important role in diabetic complications involving the kidney, nerves, retina, lens and cardiac muscle. To investigate the influence of thyroid hormone on the sorbitol pathway, we studied the effects of thyroid hormone on polyol metabolism in normal and diabetic rats. Rats were divided into three groups: controls, streptozotocin (STZ)-induced diabetic euthyroid rats (DM) and STZ-induced diabetic hyperthyroid (thyroxine-injected) rats (DM+HT). The sorbitol (Sor) concentrations in the kidney, liver and sciatic nerve (2.53+/-0.74, 0.97+/-0.16 and 24.0+/-5.1 nmol/mg protein, respectively) of the DM rats were significantly higher than those (1.48+/-0.31, 0.58+/-0.13 and 3. 1+/-0.6 nmol/mg protein) of the control rats. The Sor concentrations in the kidney and sciatic nerve of the DM+HT rats (1.26+/-0.29 and 9. 40+/-1.2 nmol/mg protein) were significantly lower than those in the DM rats. These values were reduced in the liver, unchanged in the kidney, and increased in the sciatic nerve from the hyperthyroid rats without diabetes. Thyroid hormone reduced the aldose reductase (AR) activities in the kidney, liver and sciatic nerve of the DM rats, and similarly reduced AR in the kidney and liver, but not in the sciatic nerve, of the non-diabetic rats. The sorbitol dehydrogenase (SDH) activities were decreased by thyroid hormone in the kidney and liver but not the sciatic nerve of DM rats. In the non-diabetic rats, this enzyme activity was decreased in liver, but not in kidney or sciatic nerve. A positive correlation between the Sor concentration and AR activity was observed in the kidney and liver but not in the sciatic nerve from control, DM and DM+HT rats. A negative correlation was observed between the Sor concentration and SDH activities in the same organs. These data suggest that thyroid hormone affects the sorbitol pathway, but the detailed mechanism whereby this hormone reduces the sorbitol content (especially in diabetic rats) remains to be clarified.

Aldehyde Reductase

Baroreflex control of muscle sympathetic nerve activity is attenuated in the elderly.

To determine whether the baroreflex control of sympathetic nerve activity is attenuated in the elderly, muscle sympathetic nerve activity (MSNA) from the tibial nerve was monitored using microneurography, and heart rate and blood pressure were recorded during the depressor (phase II) or pressor (phase IV) period to Valsalva's maneuver in 10 younger subjects and 7 aged subjects. The baroreflex slope for heart rate showed attenuation in the aged subjects during the pressor phase but not during the depressor phase, the baroreflex slope for MSNA was also attenuated in the aged subjects during the pressor and tended to be attenuated during the depressor phases. These data suggest impaired baroreflex function for both heart rate and sympathetic nerve activity in the elderly.

Adult

Vasodilator component in sympathetic nerve activity destined for the skin of the dorsal foot of mildly heated humans.

1. Skin sympathetic nerve activity (SSNA) was recorded in seven male subjects from the peroneal nerve by microneurography, and the temporal correspondence of spontaneously occurring SSNA bursts with vasodilatation and sweating responses on the dorsal foot was studied during a mild body heating at rest. 2. Some SSNA bursts were followed by a sweat expulsion with a latency of 2.4 +/- 0.4 s, and some bursts by a transient vasodilatation with a latency of 2.2 +/- 0.4 s (means +/- S.D.). SSNA bursts followed both by a sweat expulsion and by a vasodilatation response (Type 1), those followed only by a sweat expulsion (Type 2) and those followed only by a vasodilatation, response (Type 3) were 70%, 10% and 1% of the total bursts examined, respectively. 3. For Type 1 bursts, there was a significant, but weak linear relationship among the burst amplitude, the amplitude of the corresponding vasodilatation and the amplitude of the corresponding sweat expulsion. 4. It was concluded that SSNA contains vasodilatory activity which is synchronous with sudomotor nerve activity. The results suggest that such vasodilatory activity contributes to sustaining the sweat gland function by supplying sufficient blood.

Adult

Characteristic MR features of encephalitis caused by Epstein-Barr virus: a case report.

An 8-year-old girl showed symptoms of encephalitis during acute Epstein-Barr virus (EBV) infection. The diagnosis of EB virus infection was made by changes in the titres of EB virus-specific antibody. Cranial MRI demonstrated abnormal low and high signal intensities in the striatal body (putamen and caudate nucleus) on T1-weighted and T2-weighted images, respectively, during the acute phase. These abnormal findings had almost completely resolved 1 month later. EBV infection should be considered when lesions are localised to the basal ganglia.

Caudate Nucleus

Isolated lissencephaly sequence with balanced chromosome translocation involving 17p13.3.

We describe a patient with isolated lissencephaly sequence (ILS) who had a de novo balanced translocation with breakpoint at 8p11.23 and 17p13.3. She developed infantile spasms and had severe developmental delay. There was no apparent deletion of 17p13.3 on fluorescence in situ hybridization (FISH) analysis. The breakpoint was located centromeric to the Miller-Dieker syndrome (MDS) marker (D17S379), and telomeric to the marker D17S1566, which is located centromeric to the LIS1 gene. This is the second reported case of ILS with balanced translocation. It is suspected that the breakpoint of 17p13.3 in this patient is located in the responsible gene for ILS.

Brain

Effects of thyroid hormone on catecholamine and its metabolite concentrations in rat cardiac muscle and cerebral cortex.

Clinical and experimental data suggest that thyroid hormone affects the actions of catecholamine (CA). However, the serum or tissue levels of CA during thyroid disorders have not been well defined. Accordingly, we investigated the levels of CA and their metabolites in the cardiac muscle, the cerebral cortex, and the plasma of rats with hyperthyroidism and hypothyroidism versus euthyroid animals. The Neurochem analyzer system (ESA, Inc., Bedford, MA) was used in such determinations. The cardiac muscles of hyperthyroid rats exhibited a 16% decrease in the levels of 1-dopa, 3-methoxytyramine (3-MT) and homovanillic acid (HVA) as compared with those in euthyroid rats. The levels of norepinephrine (NE) in cardiac muscle of these rats increased significantly (5.2-fold) relative to the levels in euthyroid rats. NE was undetectable in the cardiac muscles of the hypothyroid rats. Epinephrine (E) and dopamine (DA) were not detected in the cardiac muscles of the rats with either thyroid disorder. Levels of E and 3,4-dihydroxymandelic acid (DOPEG) were detected only in the cerebral cortex of hyperthyroid rats. The cerebral cortex levels of 3-methyoxytyramine (3-MT), 3,4-dihydroxyphenylacetic acid (DOPAC), metanephrine (MN), and homovanillic acid (HVA) were all significantly increased in the hyperthyroid versus the euthyroid rats. The cerebral cortex levels of DA, NE, normetanephrine (NMN), and VMA in the hyperthyroid rats all showed a significant decrease. Levels of NE, NMN, and DOPAC in the cerebral cortex increased significantly in the hypothyroid rats. The level of VMA was undetectable in cerebral cortex of such animals. Data from studies on cardiac muscle and cerebral cortex indicate that the changes in CA and CA metabolites are responsible in part for the cardiovascular and the central nervous system symptoms observed in hyperthyroidism and hypothyroidism.

Animals

Vitamin E and coenzyme Q concentrations in the thyroid tissues of patients with various thyroid disorders.

To clarify the different roles of free radical scavenging systems in various thyroid disorders, we measured the levels of alpha-, beta-, and gamma-tocopherols and coenzyme Q in the thyroid tissues of patients with thyroid tumors and Graves' disease using high-performance liquid chromatography. The levels of alpha-tocopherols and gamma-tocopherols in the thyroid tissue of patients with papillary carcinoma and the level of gamma-tocopherol in the thyroid tissue of patients with malignant lymphoma were elevated compared with those in normal thyroid tissues. The level of coenzyme Q was reduced in the thyroid tissue of patients with Graves' disease and follicular and papillary thyroid carcinomas. These findings imply that vitamin E and coenzyme Q as scavengers play some role in thyroid follicular cell hyperfunction or dysfunction.

Graves Disease

Responses of muscle sympathetic nerve activity to lower body positive pressure.

To evaluate the response of vasomotor sympathetic nerve activity to lower body positive pressure (LBPP), muscle sympathetic nerve activity (MSNA) was microneurographically recorded from the tibial nerve in 10 healthy young men, along with hemodynamic variables and echocardiogram, during exposure to incremental LBPP at 10, 20, and 30 mmHg in the supine position. MSNA was suppressed to a similar extent (27%) at 10- and 20-mmHg LBPP. However, at 30-mmHg LBPP, MSNA tended to increase but was still nearly at the control value. Mean arterial pressure was elevated (11%), total peripheral resistance markedly increased (36%), and stroke volume and cardiac output tended to decrease at 30-mmHg LBPP. Heart rate remained unchanged throughout the procedures. Left atrial dimension significantly increased during 10- and 30-mmHg LBPP, indicating an increased cardiac filling. These results suggest that the inhibitory effect of the cardiopulmonary baroreflex on MSNA at 10- and 20-mmHg LBPP could be counteracted by the sympathoexcitatory effect of the intramuscular pressure-sensitive mechanoreflex at 30-mmHg LBPP. However, the increment of total peripheral resistance at 30-mmHg LBPP may not depend exclusively on this small enhancement of MSNA.

Adult

Gender difference in age-related changes in muscle sympathetic nerve activity in healthy subjects.

Muscle sympathetic nerve activity (MSNA) was measured directly along with blood pressure at rest in 69 healthy women (20-79 yr old) and 76 age-matched healthy men (16-80 yr old). All were nonobese and normotensive. In the women and men the MSNA was positively correlated with age (women: y = 0.788x - 5.418, r = 0.846, P < 0. 0001; men: y = 0.452x + 12.565, r = 0.751, P < 0.0001). The regression intercept of y was significantly lower (P < 0.0001) in the women than in the men, and the regression slope was significantly steeper (P < 0.0001) in the women. The MSNA was lower in women than in men among those <30 (P = 0.0012), 30-39 (P = 0. 0126), and 40-49 yr old (P = 0.0462) but was similar in women and men among those 50-59 (P = 0.1911, NS) and >/=60 yr old (P = 0.1739, NS). The results suggest that MSNA increases with age in women and men and that the activity is markedly lower in young women than in men but is markedly accelerated with age.

Adolescent

Head-up suspension in humans: effects on sympathetic vasomotor activity and cardiovascular responses.

We hypothesized that muscle sympathetic nerve activity (MSNA) and cardiovascular responses to the conventional head-up tilt (HUT) are different from those to head-up suspension (HUS) because of antigravity muscle activity. The MSNA from the tibial nerve, heart rate, blood pressure, stroke volume, cardiac output, and calf blood flow were measured in 13 healthy young subjects. Left atrial diameter was measured by two-dimensional echocardiography in another nine subjects. The resting MSNA and cardiovascular responses at a low level (20 degrees) of orthostasis were similar during both modes. At higher levels (40 and 60 degrees), the responses of MSNA, heart rate, stroke volume, and cardiac output were significantly stronger and there was a smaller reduction in calf blood flow during HUT than during HUS (P < 0.05). Left atrial diameter was decreased significantly from the resting values during HUT and HUS without any significant difference between the modes of orthostasis. The results provide evidence that the engagement of antigravity muscles during HUT may have additive effects on sympathetic vasoconstrictor and cardiovascular responses to orthostatic stress.

Adult

Microneurographic research on sympathetic nerve responses to environmental stimuli in humans.

The sympathetic nervous system plays an important role to maintain the homeostasis of vital functions in humans against environmental stimuli. Sympathetic nerve responses to environmental stimuli in humans have been assessed conventionally using rather indirect methods by analyzing the responses of effector organs or by measuring the changes in plasma norepinephrine level. Meanwhile, the microneurography technique has enabled us to approach the sympathetic nervous system in humans more directly. By applying this technique, it has become possible to investigate how the human sympathetic nervous system responds to different kinds of environmental stimuli. In this paper, the usefulness of microneurography as a research tool in environmental physiology is shown together with a review of microneurographic findings on sympathetic nerve responses to environmental stimuli in humans.

Aging

[A case of juvenile type dentatorubral-pallidoluysian atrophy (DRPLA) with psychomotor retardation since infancy].

We report here a case of an 11-year-old boy with juvenile type of dentatorubral-pallidoluysian atrophy (DRPLA). His psychomotor development has been delayed since infancy and cerebellar ataxia was noted at the age of 2 years, indicating an early onset. At the age of 6 years, he had progressive myoclonus epilepsy (PME) and underwent a series of neuroradiological, electrophysiological and pathological examinations, which failed to reveal the etiology. Gene analysis performed at the age of 11 years revealed an expanded CAG repeat at the DRPLA locus in both the patient and his asymptomatic father. In the absence of a positive family history, a diagnosis of DRPLA may be difficult due to its clinical variability. We conclude that DRPLA should be taken into account in the differential diagnosis of childhood PME and that gene analysis should be performed to confirm a diagnosis of DRPLA.

Anticipation, Genetic