Biomedical subjects

R Kawashima

Publications and source records attributed to R Kawashima.

At least 55 records · Page 3Linked to original sources

PubMed1999

Effect of 5-fluorouracil on cell cycle regulatory proteins in human colon cancer cell line.

We investigated the effects of 5-fluorouracil (5-FU) on cell cycle-regulating proteins in RPMI 4788 cells. 5-FU inhibited cell growth dose-dependently and this growth inhibition was accompanied with cell cycle accumulation in early S phase and increased expression of cyclin A. When cells were released from short-term treatment (3 or 24 h) with 5-FU, the cell cycle started to progress again and cyclin A protein levels decreased. Cyclin A-associated kinase activity assay showed that cyclin A-cyclin-dependent kinase (Cdk) 2 kinase activity was altered by 5-FU treatment concomitantly with the changes in cell cycle state seen in flow cytometric analysis. Furthermore, the elevation of cyclin A protein level by 5-FU treatment was observed in three other human cancer cell lines, DLD-1, H226Br and T.Tn. These results suggest that cyclin A protein levels in cancer cells are increased by 5-FU, and the cyclin A function and degradation mechanism remain normal.

Antimetabolites, Antineoplastic↗

PubMed1999

Tc-99m HMPAO SPECT in the evaluation of Alzheimer's disease: correlation between neuropsychiatric evaluation and CBF images.

The purpose of this study was to evaluate the effects of various covariants on the distribution pattern of Tc-99m HMPAO in patients with Alzheimer's disease by correlation analysis. Twenty patients with Alzheimer's disease and 15 age matched normal subjects participated. Tc-99m HMPAO brain SPECT and x ray computed tomography (CT) were acquired for each subject. SPECT images were transformed to a standard size and shape by automated image registration (AIR) and were used for group comparison by means of SPM96. Voxel based covariance analysis was performed on standardised images taking the age of patients, severity of disease (clinical dementia rating scale, mini mental state examination, physical self maintenance scale), and atrophy indices as variables. There was significantly decreased regional cerebral blood flow (rCBF) in the frontal, parietal, and temporal regions in the patient group (p<0.001), more marked in those patients having severe dementia. Covariance analysis disclosed that aging and severity of disease have a pronounced effect on rCBF, especially that of the left parietal region.

Aged↗

PubMed1999

Activation of the right inferior frontal cortex during assessment of facial emotion.

We measured regional cerebral blood flow (rCBF) using positron emission tomography (PET) to determine which brain regions are involved in the assessment of facial emotion. We asked right-handed normal subjects to assess the signalers' emotional state based on facial gestures and to assess the facial attractiveness, as well as to discriminate the background color of the facial stimuli, and compared the activity produced by each condition. The right inferior frontal cortex showed significant activation during the assessment of facial emotion in comparison with the other two tests. The activated area was located within a triangular area of the inferior frontal cortex in the right cerebral hemisphere. These results, together with those of previous imaging and clinical studies, suggest that the right inferior frontal cortex processes emotional communicative signals that could be visual or auditory and that there is a hemispheric asymmetry in the inferior frontal cortex in relation to the processing of emotional communicative signals.

Adult↗

PubMed1999

Parametric mapping of cerebral blood flow deficits in Alzheimer's disease: a SPECT study using HMPAO and image standardization technique.

UNLABELLED: This study assessed the accuracy and reliability of Automated Image Registration (AIR) for standardization of brain SPECT images of patients with Alzheimer's disease (AD). Standardized cerebral blood flow (CBF) images of patients with AD and control subjects were then used for group comparison and covariance analyses. METHODS: Thirteen patients with AD at an early stage (age 69.8+/-7.1 y, Clinical Dementia Rating Score 0.5-1.0, Mini-Mental State Examination score 19-23) and 20 age-matched normal subjects (age 69.5+/-8.3 y) participated in this study. 99mTc-hexamethyl propylenamine oxime (HMPAO) brain SPECT and CT scans were acquired for each subject. SPECT images were transformed to a standard size and shape with the help of AIR. Accuracy of AIR for spatial normalization was evaluated by an index calculated on SPECT images. Anatomical variability of standardized target images was evaluated by measurements on corresponding CT scans, spatially normalized using transformations established by the SPECT images. Realigned brain SPECT images of patients and controls were used for group comparison with the help of statistical parameter mapping. Significant differences were displayed on the respective voxel to generate three-dimensional Z maps. CT scans of individual subjects were evaluated by a computer program for brain atrophy. Voxel-based covariance analysis was performed on standardized images with ages and atrophy indices as independent variables. RESULTS: Inaccuracy assessed by functional data was 2.3%. The maximum anatomical variability was 4.9 mm after standardization. Z maps showed significantly decreased regional CBF (rCBF) in the frontal, parietal and temporal regions in the patient group (P < 0.001). Covariance analysis revealed that the effects of aging on rCBF were more pronounced compared with atrophy, especially in intact cortical areas at an early stage of AD. Decrease in rCBF was partly due to senility and atrophy, however these two factors cannot explain all the deficits. CONCLUSION: AIR can transform SPECT images of AD patients with acceptable accuracy without any need for corresponding structural images. The frontal regions of the brain, in addition to parietal and temporal lobes, may show reduced CBF in patients with AD even at an early stage of dementia. The reduced rCBF in the cortical regions cannot be explained entirely by advanced atrophy and fast aging process.

Aged↗

PubMed1999

Anatomic validation of spatial normalization methods for PET.

UNLABELLED: Spatial normalization methods, which are indispensable for intersubject analysis in current PET studies, have been improved in many aspects. These methods have not necessarily been evaluated as anatomic normalization methods because PET images are functional images. However, in view of the close relation between brain function and morphology, it is very intriguing how precisely normalized brains coincide with each other. In this report, the anatomic precision of spatial normalization is validated with three different methods. METHODS: Four PET centers in Japan participated in this study. In each center, six normal subjects were recruited for both H2(15)O-PET and high-resolution MRI studies. Variations in the location of the anterior commissure (AC) and size and contours of the brain and the courses of major sulci were measured in spatially normalized MR images for each method. Spatial normalization was performed as follows. (a) Linear: The AC-posterior commissure and midsagittal plane were identified on MRI and the size of the brain was adjusted to the Talairach space in each axis using linear parameters. (b) Human brain atlas (HBA): Atlas structures were manually adjusted to MRI to determine linear and nonlinear transformation parameters and then MRI was transformed with the inverse of these parameters. (c) Statistical parametric mapping (SPM) 95: PET images were transformed into the template PET image with linear and nonlinear parameters in a least-squares manner. Then, coregistered MR images were transformed with the same parameters used for the PET transformation. RESULTS: The AC was well registered in all methods. The size of the brain normalized with SPM95 varied to a greater extent than with other approaches. Larger variance in contours was observed with the linear method. Only SPM95 showed significant superiority to the linear method when the courses of major sulci were compared. CONCLUSION: The results of this study indicate that SPM95 is as effective a spatial normalization as HBA, although it does not use anatomic images. Large variance in structures other than the AC and size of the brain in the linear method suggests the necessity of nonlinear transformations for effective spatial normalization. Operator dependency of HBA also must be considered.

Brain↗

PubMed1998

Participation of the prefrontal cortices in prospective memory: evidence from a PET study in humans.

Prospective memory is a memory feature in humans which involves activities for remembering to do something in the future. The present study provides functional neuroanatomy of prospective memory for the first time. We used positron emission tomography (PET) and found several localized brain activations in relation to a prospective memory task required to retain and remember a planned action while performing an ongoing routine activity. Activations were identified in the right dorsolateral and ventrolateral prefrontal cortices, the left frontal pole and anterior cingulate gyrus, the left parahippocampal gyrus, and midline medial frontal lobe. We attributed these activations to several cognitive processes involved in prospective memory, such as holding an intention toward future behavior, checking target items within presented stimuli, and dividing attention between the planned action and the routine activity.

Adult↗

PubMed1998

The role of the left inferior temporal cortex for visual pattern discrimination--a PET study.

We measured regional cerebral blood flow using positron emission tomography in seven normal volunteers during discrimination tasks for visual patterns. For the 'attention to right or left' tasks, the subjects were instructed to press a key when sample and test stimuli presented in the right or left visual fields, respectively, were identical. In the control task, subjects were instructed to press a key on every second presentation of the test stimulus. Both discrimination tasks activated the same area in the inferior temporal sulcus of the left hemisphere. The results indicate that the left inferior temporal cortex plays a dominant role in the discrimination of visual pattern in right handed subjects.

Adult↗

PubMed1998

Shape and roughness activate different somatosensory areas in the human brain.

Somatosensory stimuli are known to activate the postcentral gyrus, and neurons there fire when the skin is in contact with objects. Also neurons in the lateral fissure, the parietal operculum, fire when rough surfaces are felt. However the localization of somatosensory association areas in humans is largely unknown and differences in functional contributions between somatosensory association areas has not been previously demonstrated. For these reasons the regional cerebral blood flow was measured with 15O-butanol and positron-emission tomography in two groups of young volunteers discriminating the lengths, shapes, and roughness of objects with their right hand. Roughness discrimination activated the lateral parietal opercular cortex significantly more than did length or shape discrimination. A Boolean intersection of the cluster images showing the statistical significant increases of length and shape discrimination demonstrated that shape and length discrimination activated the same cortical field lining the anterior part of the intraparietal sulcus (IPA). Shape and length discrimination activated IPA significantly more than did roughness discriminaton. These findings demonstrate a separation in functional contributions of lateral parietal opercular cortex and IPA. The results indicate different cortical processing streams for the somatosensory submodalities microgeometry and macrogeometry.

Adult↗

PubMed1998

Neuroanatomical correlates of the assessment of facial attractiveness.

Frontal cortical damage can lead to changes in affective aspects of personality. However, the difficulty of dissociating such abnormalities from cognitive disorders has overshadowed most previous findings. Regional cerebral blood flow (rCBF) was measured with positron emission tomography (PET) while normal subjects were assessing facial attractiveness. Two left frontal regions showed a significant increase in rCBF while assessing facial attractiveness. The increased rCBF in the left anterior frontal cortex correlated with the overall percentage of assessments of a face as unattractive, while that in the left fronto-temporal junction correlated with the percentage of assessments of a face as attractive. These findings provide direct evidence that the left frontal regions are engaged in the assessment of facial attractiveness.

Adult↗

PubMed1998

A PET study of axis orientation discrimination.

We examined the cortical areas showing increased activation related to axis orientation discrimination in hand movement and perception by positron emission tomography (PET) in right-handed normal human subjects while they performed a hand orientation (HO) task and an orientation discrimination (OD) task. In the OD task, fields in the parietal cortex and a field in the inferior frontal gyrus showed increased activation relative to the control task. In the HO task, fields in the intraparietal sulcus, the inferior and middle frontal gyri, the fusiform gyrus and the middle temporal gyrus showed increased activation relative to the control task. The results indicate that areas involved in axis orientation discrimination seemed to be segregated in the parietal cortex, with one field in the left intraparietal sulcus related to hand movement and another field in the right intraparietal sulcus related to perception.

Adult↗

PubMed1998

Influence of ANOVA design and anatomical standardization on statistical mapping for PET activation.

We have created images of z value, error, and variation components for a PET activation study using various ANOVA designs and anatomical standardization methods. Data were acquired in four PET centers. In each center, CBF was measured on six normal male subjects under resting and covert verb generation, three times for each. The images were anatomically standardized with LINEAR transformation, SPM (Ver. 95), HBA (Karolinska/Tohoku), or MICHIGAN (Minoshima). ANOVA was performed pixel by pixel to compute t (and z) for the task main effect (Verb vs Rest) in four different designs: (i) two way (subject and task) (2W), (ii) two-way with interaction (2WI), (iii) subject considered a random factor (2WI-MX), and (iv) three-way (subject, task, and replication) (3W). A large area extending from the Broca to the left premotor cortex was activated. The localization of the highest peak depended both on the anatomical standardization and on the ANOVA design, the variation ranging 3-4 cm. Smoothing reduced the variation while erasing possible subfoci. The z images of 2W, 2WI, and 3W looked alike, whereas 2WI-MX presented lower peak z values. SPM tended to present higher z values than the other methods. The error was high in the gray and low in the white matter. The root mean square for the subject effect was high on the border of gray matter especially in LINEAR and HBA, revealing intersubject mismatch in the gray matter distribution. The root mean square for the subject-by-task interaction effect revealed individual variation in activation.

Adult↗

PubMed1998

Use of automated image registration to generate mean brain SPECT image of Alzheimer's patients.

UNLABELLED: The purpose of this study was to compute and compare the group mean HMPAO brain SPECT images of patients with senile dementia of Alzheimer's type (SDAT) and age matched control subjects after transformation of the individual images to a standard size and shape. METHODS: Ten patients with Alzheimer's disease (age 71.6 +/- 5.0 yr) and ten age matched normal subjects (age 71.0 +/- 6.1 yr) participated in this study. Tc-99m HMPAO brain SPECT and X-ray CT scans were acquired for each subject. SPECT images were normalized to an average activity of 100 counts/pixel. Individual brain images were transformed to a standard size and shape with the help of Automated Image Registration (AIR). Realigned brain SPECT images of both groups were used to generate mean and standard deviation images by arithmetic operations on voxel based numerical values. Mean images of both groups were compared by applying the unpaired t-test on a voxel by voxel basis to generate three dimensional T-maps. X-ray CT images of individual subjects were evaluated by means of a computer program for brain atrophy. RESULTS: A significant decrease in relative radioisotope (RI) uptake was present in the bilateral superior and inferior parietal lobules (p < 0.05), bilateral inferior temporal gyri, and the bilateral superior and middle frontal gyri (p < 0.001). The mean brain atrophy indices for patients and normal subjects were 0.853 +/- 0.042 and 0.933 +/- 0.017 respectively, the difference being statistically significant (p < 0.001). CONCLUSION: The use of a brain image standardization procedure increases the accuracy of voxel based group comparisons. Thus, intersubject averaging enhances the capacity for detection of abnormalities in functional brain images by minimizing the influence of individual variation.

Aged↗

PubMed1998

A comparison of Tc-99m HMPAO brain SPECT images of young and aged normal individuals.

The purpose of this study was to examine the normal distribution patterns of 99mTc-HMPAO (HMPAO) in young and aged normal individuals and to clarify differences between the distribution patterns of the two groups by means of an anatomical standardization technique. The tracer distribution was measured with HMPAO and SPECT in 18 normal subjects; age range 20-81 yrs. SPECT images were globally normalized by averaging whole brain radioactivity counts to 100 counts/voxel. The SPECT images for each subject were transformed into the standard brain anatomy by means of a computerized brain atlas, together with each subject's CT images. Mean and SD images for young (28.8 +/- 6.4 yrs) and aged groups (62.3 +/- 10.2 yrs) were then calculated on a voxel-by-voxel basis. Statistically significant differences between young and aged groups were observed in the relative tracer distribution patterns. In the aged group, relative decreases were found in the cortical areas of the frontal and temporal lobes, limbic areas and basal ganglia regions. The results, as visualized changes in tracer distribution patterns with aging, may contribute to more accurate clinical diagnosis.

Adult↗

PubMed1998

Oculomotor sequence learning: a positron emission tomography study.

The purpose of this study was to identify the brain regions activated in relation to oculomotor sequence learning. Nine healthy subjects participated in the study, which consisted of three positron emission tomography scans. In the initial learning task, subjects were instructed to track a sequence of seven successive positions of visual targets and to memorize the order of the targets as well as their spatial locations. In the saccade task, subjects were instructed to track visual targets presented at random locations. In the control task, subjects were instructed to gaze at a fixation point. Fields showing significant regional cerebral blood flow change were determined from task-minus-control subtraction images. We determined that fields in the pre-supplementary motor area (pre-SMA), the intraparietal cortex, and the prefrontal cortex were activated not only in the learning-minus-control images but also in the learning-minus-saccade images. Although prefrontal and parietal activations were bilateral, pre-SMA activation was confined to the left hemisphere. The results indicate that these fields function as a part of the neural network involved in the learning of sequential saccadic eye movements.

Adolescent↗

PubMed1998

Regional cerebral blood flow changes in human brain related to ipsilateral and contralateral complex hand movements--a PET study.

The purpose of this study was to investigate the cortical motor areas activated in relation to unilateral complex hand movements of either hand, and the motor area related to motor skill learning. Regional cerebral blood flow (rCBF) was measured in eight right-handed healthy male volunteers using positron emission tomography during a two-ball-rotation task using the right hand, the same task using the left hand and two control tasks. In the two-ball-rotation tasks, subjects were required to rotate the same two iron balls either with the right or left hand. In the control task, they were required to hold two balls in each hand without movement. The primary motor area, premotor area and cerebellum were activated bilaterally with each unilateral hand movement. In contrast, the supplementary motor area proper was activated only by contralateral hand movements. In addition, we found a positive correlation between the rCBF to the premotor area and the degree of improvement in skill during motor task training. The results indicate that complex hand movements are organized bilaterally in the primary motor areas, premotor areas and cerebellum, that functional asymmetry in the motor cortices is not evident during complex finger movements, and that the premotor area may play an important role in motor skill learning.

Adult↗

PubMed1998

Follow-up of improvement in regional cerebral blood flow and mental status in Alzheimer's disease: a case report.

Cerebral SPECT imaging has the potential to make important contributions in the follow-up care of patients with Alzheimer's disease. An unusual case of a patient who showed a follow-up cerebral blood flow pattern different from that routinely seen in Alzheimer's disease patients is reported here. Qualitative and voxel-based objective evaluation of follow-up scans revealed improvement in parietotemporal deficits that had been observed on a baseline study. This change was observed without significant further deterioration in ratings by dementia batteries. This case shows that a baseline regional cerebral blood flow study might be necessary for reference and comparison in the proper follow-up care of Alzheimer's disease patients.

Aged↗

PubMed1998

Regional cerebral blood flow abnormalities in late-life depression: relation to refractoriness and chronification.

We examined patterns of regional cerebral blood flow (rCBF) abnormalities in 18 patients with major depressive disorder in late life using single photon emission computed tomography (SPECT) and 99mTc-hexamethylpropylenamine oxime (99mTc-HMPAO). Compared with 13 age-matched controls, relative rCBF was significantly decreased bilaterally in the anterior cingulate gyrus, the prefrontal cortex, the temporal cortex, the parietal cortex, the hippocampus and the caudate nucleus. However, it was not correlated with the severity of depression or global cognitive dysfunction. In 10 patients with a prolonged depressive episode or prolonged residual symptoms (the refractory subgroup), robust and extensive decreases in rCBF were found compared with controls and the rCBF decreased significantly in the anterior cingulate gyrus and the prefrontal cortex compared with that in the non-refractory subgroup. In the non-refractory subgroup, rCBF decreased significantly in the caudate nucleus and tended to decrease in the anterior cingulate gyrus compared with controls. These findings indicate that dysfunction of the limbic system, the cerebral association cortex and the caudate nucleus may be implicated in late-life depression and that robust and extensive hypoperfusion, especially in the anterior cingulate and the prefrontal regions, may relate to refractoriness or chronification of depression.

Aged↗

PubMed1998

Menstrual disorders in patients undergoing chronic hemodialysis.

OBJECTIVE: To investigate the etiology of menstrual disorders in patients undergoing chronic hemodialysis (CHD). METHODS: The menstrual histories, along with hormonal, biochemical, and hematological data, were investigated in 25 reproductive-aged CHD patients. RESULTS: All subjects had had regular menstrual cycles before entering CHD therapy. Of the 20 women who developed amenorrhea after beginning CHD therapy, 8 showed a return to their regular cycles and 6 improved to oligomenorrhea, 3 months to 66 months later, while 6 remained amenorrheic. The serum prolactin (PRL) levels were significantly higher in the patients (n = 9) with normogonadotropic amenorrhea or oligomenorrhea than in patients (n = 13) with regular cycles (53.6 +/- 36.2 vs 27.8 + 15.2 ng/ml, p < 0.05). The serum LH levels were high in both groups. In a cross-sectional study, the serum PRL levels gradually decreased with longer duration of dialysis. CONCLUSIONS: Patients undergoing CHD are likely to develop menstrual disorders. Hyperprolactinemia in part contributes to these menstrual disorders. However, menstrual disorders in CHD patients tend to improve during long-term follow-up, because of the gradual decrease in serum PRL levels during long-term CHD therapy.

Adult↗