Biomedical subjects

H Fukuyama

Publications and source records attributed to H Fukuyama.

At least 91 records · Page 5Linked to original sources

PubMed1998

Diurnal change of the cold-inducible RNA-binding protein (Cirp) expression in mouse brain.

RNA-binding proteins are believed to play important roles in regulation of neural functions. Recently, a mouse cDNA encoding the cold-inducible RNA-binding protein, Cirp, has been isolated, the amino acid sequence of which showed similarity to plant circadian rhythm proteins. In the present study, diurnal expression of Cirp in the mouse nervous system was examined. Northern blot analysis showed that the level of Cirp mRNA was diurnally regulated in the brain but not in the testis and liver. The level increased during the daytime and decreased during the nighttime. Immunohistochemistry using an anti-Cirp antibody showed that Cirp was expressed in the nucleus of neurons and that the level of Cirp was diurnally regulated in the suprachiasmatic nucleus and the cerebral cortex. The diurnal regulation was not observed in the brain of adult mice kept in constant darkness nor that of 3-day-old mice. These findings suggest that Cirp plays a role in biological rhythms as known for plant proteins and that expression of Cirp is regulated differentially in discrete brain regions.

Animals↗

PubMed1998

Transgenic expression of Fas in T cells blocks lymphoproliferation but not autoimmune disease in MRL-lpr mice.

Fas is a member of the TNF receptor family. Binding of Fas ligand to Fas induces apoptosis in Fas-bearing cells. Fas is expressed in various cells, including thymocytes, peripheral T cells, and activated B cells. The mouse lpr mutation is a loss of function mutation of Fas. MRL-lpr/lpr mice develop lymphadenopathy and splenomegaly, and produce multiple autoantibodies, which results in autoimmune disease. In this report, we describe the establishment of a line of Fas transgenic MRL-lpr mice in which mouse Fas cDNA was expressed using the T cell-specific murine lck promoter. The transgenic mice expressed functional Fas in thymocytes and peripheral T cells, but not in B cells. The transgenic mice did not accumulate abnormal T cells (Thy-1+ B220+), but still accumulated B cells (Thy-1- B220+); they produced a large quantity of Igs (IgG1 and IgG2a), including anti-DNA Abs, and developed glomerulonephritis. These results suggest that autoreactive or activated B cells must be killed through Fas expressed in the B cells by the Fas ligand expressed in activated T cells.

Animals↗

PubMed1998

Atrophy of the corpus callosum, cortical hypometabolism, and cognitive impairment in corticobasal degeneration.

OBJECTIVE: To investigate whether atrophy of the corpus callosum is associated with cognitive impairment and cerebral cortical hypometabolism in corticobasal degeneration. DESIGN: Prospective clinicoradiological correlation with magnetic resonance imaging and positron emission tomography. SETTING: A university hospital. PATIENTS: Eight right-handed patients with clinically diagnosed corticobasal degeneration (mean+/-SD age, 64+/-8 years). MAIN OUTCOME MEASURES: Midsagittal corpus callosum area-skull area ratio (on T1-weighted magnetic resonance images), the sum of the scaled scores of the 6 subtests on the Wechsler Adult Intelligence Scale-Revised (Digit Span, Arithmetic, Picture Arrangement, Object Assembly, Block Design, and Digit Symbol), and cerebral metabolic rate of glucose (measured with positron emission tomography by using fludeoxyglucose F 18 as a tracer). RESULTS: Compared with 36 age-matched right-handed control subjects, the patients had significantly decreased callosal area-skull area ratio. The reduction in this ratio was greatest in the middle half of the corpus callosum. The atrophy of the corpus callosum was accompanied by a decreased mean cortical glucose metabolic rate with hemispheric asymmetry and a decrease in the sum of the scaled subtest scores of the Wechsler Adult Intelligence Scale-Revised. CONCLUSIONS: Atrophy of the corpus callosum with middle predominance is present in corticobasal degeneration, and this atrophy is associated with cognitive impairment and cerebral cortical hypometabolism with hemispheric asymmetry. Atrophy of the corpus callosum might reflect the severity of the disconnection between cortical regions, and this may be an important factor in the development of cerebral cortical dysfunction in corticobasal degeneration.

Aged↗

PubMed1998

Electrophysiological studies of early stage corticobasal degeneration.

We conducted electrophysiological studies in two Asian patients with probable corticobasal degeneration (CBD). The duration of illness from onset was 16 and 20 months, respectively. The clinical manifestations were markedly asymmetric and characterized by cortical sensory loss, apraxia, action myoclonus, action tremor, and akinetic-rigid parkinsonism. Neither patient responded to levodopa therapy. Simple photon-emission computed tomography (SPECT) study showed significantly decreased regional cerebral blood flow in the frontoparietal areas and thalamus opposite to the predominantly affected limb. A series of electrophysiological studies failed to identify giant somatosensory evoked potentials (SEPs), enhanced long latency electromyography (EMG) reflex, and cortical spikes preceding myoclonic jerk. However, the earliest cortical component of the median nerve SEP was exclusively enlarged in one patient and preserved with depression of the subsequent components in the other patient. Significantly shorter postmotor-evoked potential (MEP) silent period was found after the transcranial magnetic stimulation of the motor cortex in both patients. CBD is a unique clinical entity characterized by action myoclonus probably the result of the pathologic hyperexcitability of the motor cortex, based on a loss of inhibitory input from the sensory cortex.

Aged↗

PubMed1998

Retroperitoneal leiomyosarcoma of a male centenarian.

An autopsy case of retroperitoneal leiomyosarcoma of a centenarial male is described. He complained of abdominal pain in his left side 1 month before his death. Ultrasonography and computed tomography revealed a large mass in the left abdominal cavity. At autopsy, a circumscribed mass, 15 cm in diameter, was found in the left-upper abdominal cavity, and seemed to be derived from the retroperitoneum in an exophytic manner. Histologically, spindle cells with slight eosinophilic cytoplasm and blunt-ended nuclei showed interwoven fascicular growth, and mitotic figures were easily encountered. Immunohistochemically, the tumor cells were labeled by alpha-smooth muscle actin and vimentin. To our knowledge, this case of leiomyosarcoma has presented in the oldest patient ever reported. The rarity of soft tissue sarcomas in the extremely elderly is also discussed.

Aged↗

PubMed1998

Clinical usefulness of the dipole tracing method for localizing interictal spikes in partial epilepsy.

PURPOSE: To clarify the clinical usefulness of the dipole tracing method in evaluation of interictal EEG spikes in patients with partial epilepsy. METHODS: Eight patients with partial epilepsy were studied. We compared the generator source of interictal spikes detected by the dipole tracing method with the results of magnetic resonance imaging (MRI), interictal/ictal measurement of cerebral blood flow (CBF) by single photon emission computed tomography (SPECT), interictal measurement of glucose metabolism by positron emission tomography (PET) and invasive electrocorticogram (ECoG). RESULTS: In 5 patients with mesial temporal lobe epilepsy (TLE), including 3 patients who underwent standard temporal lobectomy, the dipole tracing method showed results consistent with those of other examinations and better correlation with ECoG than with other noninvasive examinations. In a patient with mesial TLE who had defects in the skull due to previous surgery, the dipoles were located more laterally than expected. In a patient with frontal lobe epilepsy (FLE) who was finally proved to have an epileptogenic area in the lateral frontal area, the spike dipoles were identified in the medial side of the frontal lobe. CONCLUSIONS: The dipole tracing method used in the present study is useful for localizing epileptogenic areas in patients with mesial TLE. However, in patients with partial skull defects and in those with FLE, the reliability of this method is still in accuracy of the lobe level.

Adolescent↗

PubMed1998

Cerebral hematocrit decreases with hemodynamic compromise in carotid artery occlusion: a PET study.

BACKGROUND AND PURPOSE: This study investigated whether in patients with internal carotid artery occlusion the regional cerebral hematocrit correlates with cerebral hemodynamics or metabolic state and, if so, how the regional cerebral hematocrit changes in the hemodynamically compromised region. METHODS: We used positron emission tomography to study seven patients with unilateral internal carotid artery occlusion and no cortical infarction in the chronic stage. The distributions of red blood cell and plasma volumes were assessed using oxygen-15-labeled carbon monoxide and copper-62-labeled human serum albumin-dithiosemicarbazone tracers, respectively. The calculated hematocrit value was compared with the hemodynamic and metabolic parameters measured with the oxygen-15 steady-state technique. RESULTS: In the cerebral cortex, the value of the cerebral hematocrit varied but was correlated with the hemodynamic and metabolic status. Stepwise regression analysis revealed that the large vessel hematocrit, the cerebral metabolic rate of oxygen, and the cerebral blood flow or the oxygen extraction fraction accounted for a significant proportion of variance of the cerebral hematocrit. The oxygen extraction fraction and the cerebral metabolic rate of oxygen negatively correlated with the cerebral hematocrit, whereas the cerebral blood flow correlated positively: patients with reduced blood supply relative to metabolic demand (decreased blood flow with increased oxygen extraction fraction) showed low hematocrit values. CONCLUSIONS: In carotid artery occlusion in the chronic stage, regional cerebral hematocrit may vary according to cerebral hemodynamics and metabolic status. Regional cerebral hematocrit may decrease with hemodynamic compromise unless oxygen metabolism concomitantly decreases.

Aged↗

PubMed1998

Cortical myoclonus: sensorimotor hyperexcitability.

Cortical or cortical reflex myoclonus is characterized by abnormally enlarged cortical somatosensory evoked potentials (giant SEPs), which most likely reflect pathologically hyperexcitable sensorimotor cortex. To clarify the pathogenesis of myoclonus of cortical origin, we simultaneously recorded SEPs and whole head somatosensory evoked magnetic fields (SEFs) following electric stimulation of the median nerve at the wrist in six patients with cortical myoclonus. N20m and enlarged P30m were observed in all patients and were localized at the posterior bank of the central sulcus (Brodmann area 3b of the primary somatosensory cortex). In addition, P25m and N35m components of SEFs were recognized in five and four patients, respectively. P25m component, that is, the magnetic counterpart of P25 in EEG, was the earliest cortical component showing enhancement in patients. Multidipole analysis combined with magnetic resonance imaging (MRI) coregistration revealed that the generators of P25m were in the precentral gyrus in four patients and in the postcentral gyrus in one patient. The second SEFs around 200 msec after the single stimulus were recorded in three patients at area 3b (repetitive SEFs); two of whom showed negative as well as positive myoclonus. The importance of motor cortex for the generation of cortical reflex myoclonus was thus demonstrated. The pathologic features of SEFs suggest abnormal excitability of primary sensorimotor cortex.

Adult↗

PubMed1997

Cortical processing mechanism for vocalization with auditory verbal feedback.

To investigate the relationship between motor and sensory speech center, cortical activity was examined using PET while normal subjects perceived their own voice which sounded different to the articulated one. The results showed significant activation in the superior temporal gyri with absence of activity in the supplementary motor area (SMA). In a previous study we found significant activation in SMA with no activity in the superior temporal gyrus when normal subjects simply vocalized. Thus, two different cortical pathways for vocalization were delineated: programmed pathway in SMA, and pathway with auditory verbal feedback. The former is thought to be the mature system in the adult, and the latter may be related to speech acquisition.

Adult↗

PubMed1997

The role of the temporal coding system in the auditory cortex on speech recognition.

To elucidate the temporal coding system for speech recognition, we synthesized stimulation sounds which do not contain formant information but do contain temporal information by transforming original sound wave to click sequences. Using this stimulation sound, we performed a recognition test and used PET to examine the cortical activities in normal subjects listening to this sound. The results of the recognition test showed a good perception of the sounds made from sequential speech. The PET study demonstrated significant activation of the superior temporal gyri while listening to the stimulation speech sounds. Our results imply that these stimulation sounds were processed semantically in the auditory cortices. The temporal processing system is thought to make an important contribution to speech recognition.

Adult↗

PubMed1997

Brain functional activity during gait in normal subjects: a SPECT study.

The purpose of this study was to evaluate changes in brain activity during voluntary walking in normal subjects using technetium-99m-hexamethyl-propyleneamine oxime single photon emission computed tomography. This study included 14 normal subjects. Statistical parametric mapping analysis revealed that the supplementary motor area, medial primary sensorimotor area, the striatum, the cerebellar vermis and the visual cortex were activated. These results suggested that the cerebral cortices controlling motor functions, visual cortex, basal ganglia and the cerebellum might be involved in the bipedal locomotor activities in humans.

Adult↗

PubMed1997

Movement-related cortical potentials and regional cerebral blood flow change in patients with stroke after motor recovery.

We investigated brain activity during the self-initiated, simple, repetitive hand movement in two patients with hemiparesis due to stroke, who showed relatively good motor recovery, using movement-related cortical potential (MRCP) and regional cerebral blood flow (rCBF) measurements with positron emission tomography (PET). One patient had cortical lesions in the left premotor and left parietal cortices due to cerebral thrombosis, and the other had lesions in the right Rolandic area and several subcortical areas due to the occlusion of the right internal carotid artery. MRCPs in both patients showed lack of the contralateral predominance in amplitude of the late component of slow negative shift prior to the movement of the recovered hand. PET activation study showed increased rCBF in the ipsilateral hemisphere during the movement of the recovered hand. These findings suggest that the ipsilateral hemisphere to the recovered hand may play an important role in the process of motor recovery in patients with cortical infarction, especially within the time period of several hundred ms before the onset of each movement.

Aged↗

PubMed1997

Functional localization of pain perception in the human brain studied by PET.

To elucidate the functional localization and somatotopic organization of pain perception in the human cerebral cortex, we studied the regional cerebral blood flow using positron emission tomography during selective painful stimulation in six normal subjects. Response to a painful stimulus was elicited using a special CO2 laser, which selectively activates nociceptive receptors, to the hand and foot. Multiple brain areas, including bilateral secondary somatosensory cortices (SII) and insula, and the frontal lobe and thalamus contralateral to the stimulus side, were found to be involved in the response to painful stimulation. While our data indicate that the bilateral SII play an important role in pain perception, they also indicate that there is no pain-related somatotopic organization in the human SII or insula.

Adult↗

PubMed1997

Atrophy of the corpus callosum, cognitive impairment, and cortical hypometabolism in progressive supranuclear palsy.

Recent studies disclosed neurofibrillary degeneration in layer 3 of the association cortex in patients with progressive supranuclear palsy. This lesion may be associated with corpus callosum atrophy and may impair the function of cortical regions indispensable for complex cognitive activity. To investigate whether corpus callosum atrophy is associated with cognitive impairment and cerebral cortical hypometabolism, we studied 10 patients with progressive supranuclear palsy using magnetic resonance imaging and positron emission tomography with fluorodeoxyglucose as a tracer. Compared with 23 age-matched control subjects, the patients had significantly decreased callosal area-skull area ratios, with anterior predominance of the degree of atrophy. The corpus callosum atrophy was accompanied by a decreased mean cortical glucose metabolic rate, predominantly in the frontal region of the cortex, and poor performance on the picture arrangement subtest of the Wechsler Adult Intelligence Scale and the verbal fluency task. We conclude that corpus callosum atrophy with anterior predominance is present in progressive supranuclear palsy, and that this atrophy is associated with cognitive impairment and cerebral cortical hypometabolism, especially in the frontal cortical region. Corpus callosum atrophy may reflect the pathological changes in the cerebral cortex, accentuated in the frontal region, that contribute to the development of frontal lobe dysfunction in this disease.

Aged↗

PubMed1997

Cerebral glucose metabolism in corticobasal degeneration: comparison with progressive supranuclear palsy and normal controls.

The regional metabolic rate of glucose was estimated using 18F-labeled 2-deoxyglucose and positron-emission tomography (PET) in eight patients with corticobasal degeneration (CBD). Measures of cerebral glucose metabolism in these patients were compared with those for nine age-matched normal controls and eight patients with progressive supranuclear palsy (PSP). Compared with that in the normal controls, the CBD patients showed significantly reduced cerebral glucose metabolism in the contralateral hemisphere to the clinically most affected side in the dorsolateral frontal, medial frontal, inferior parietal, sensorimotor, and lateral temporal cortex, as well as in the corpus striatum and the thalamus. In comparison with that in PSP, in CBD the glucose metabolism in the contralateral hemisphere was significantly decreased in the inferior parietal, sensorimotor, lateral temporal cortex, and the corpus striatum. These results confirm the marked asymmetric cerebral involvement in CBD and suggest that there are significant differences between CBD and PSP in the cerebral metabolism in some cerebral regions such as the inferior parietal cortex and sensorimotor cortex, which might reflect the differences in their clinical characteristics.

Aged↗

PubMed1997

Cortical activation by monaural speech sound stimulation demonstrated by positron emission tomography.

To investigate how auditory input from each ear contributes to spoken language processing, cortical activation by monaural speech sound stimulation was examined in 12 normal subjects using 15O-labeled water positron emission tomography. Regional cerebral blood flow (rCBF) was measured under four different sound stimulation conditions: (1) silence, (2) white noise, (3) sequential Japanese sentences ("speech"), and (4) Japanese sentences played backward ("reversed speech"), and the results were evaluated by statistical parametric mapping (SPM). Noise induced significant rCBF increase in the contralateral Heschl's gyrus. Speech and reversed speech stimuli caused significant rCBF increase in the contralateral Heschl's gyrus and the bilateral superior temporal gyri, with contralateral activation broader than that in the ipsilateral hemisphere. Monaurally input speech sound signals that reach the contralateral Heschl's gyrus may be processed chiefly and phonologically in the surrounding superior temporal gyrus in the same hemisphere. Comparison of speech activation with reversed speech activation failed to demonstrate a significant difference, which made it difficult to identify the area for lexical and semantic processing.

Acoustic Stimulation↗

PubMed1997

Age-related changes in cerebral blood flow activation during a Card Sorting Test.

To determine the age-related changes in the neural processing involved in the Modified Card Sorting Test (MCST), we measured cerebral blood flow (CBF) during performance of the MCST and of the number-matching task in young and elderly subjects using positron emission tomography. Compared with that during the number-matching task, CBF during the MCST was increased in the left dorsolateral prefrontal cortex (DLPFC), left inferior parietal lobule, and left striate and prestriate cortices in both age groups. However, CBF activation in these areas was significantly lower in the elderly subjects than the young subjects. Furthermore, CBF activation was reduced in the left DLPFC, right parahippocampal gyrus, and prestriate cortex in proportion to the increase in the number of perseverative errors with aging. These results suggest that the impaired MCST performance in elderly subjects may be due, in part, to dysfunction of the network involving certain cortical areas such as the prefrontal and parahippocampal cortices, although the essential neural circuits for MCST performance were still preserved even in the elderly subjects.

Adult↗

PubMed1997

Adult onset globoid cell leukodystrophy (Krabbe disease): analysis of galactosylceramidase cDNA from four Japanese patients.

We examined galactosylceramidase (GALC) cDNA in four Japanese patients with adult onset globoid cell leukodystrophy (Krabbe disease; AO-GLD) by polymerase chain reaction/single-strand conformation polymorphism (PCR-SSCP) analysis, subsequent sequence determination, and restriction enzyme digestion of PCR products, initial symptoms were the onset of slowly progressive spastic paraplegia from the middle of the second decade, and all patients had diminished GALC activity in their leukocytes. We identified three missense mutations (I66M, G270D, L618S) and one exon-6 skipping (535-573del). Two of the patients had only the I66M mutant mRNA, and one only the G27OD mutant mRNA. The fourth patient carried a compound heterozygous mutation of 535-573del and L618S. To determine the enzymatic activities produced by these mutations, we constructed mutated GALC cDNAs and expressed them in COS-1 cells. Three mutations, viz., G270D, L618S, and exon-6 skipping (535-573del), produced diminished GALC activity as expected. The I66M mutation in the wild-type GALC cDNA(I289) had normal activity, but when this mutation and the V289 polymorphism were introduced into the same allele, it had decreased activity. Thus, the combination of a unique mutation and polymorphism causes conformational change in the GALC enzyme, resulting in low enzymatic activity. AO-GLD mutations, including those found here, are located in the N-terminus (I66M, G270D, 535-573del) or C-terminus (L618S) of the GALC enzyme, whereas the reported mutations in the infantile form (IF-GLD) are in the central domain. This difference in mutation sites may affect the clinical features of GLD.

Adult↗