Biomedical subjects

S Takashima

Publications and source records attributed to S Takashima.

At least 289 records · Page 16Linked to original sources

PubMed1997

Tuberin immunohistochemistry in brain, kidneys and heart with or without tuberous sclerosis.

We have studied immunohistochemically the expression of tuberin, the protein product of the TSC2 gene, in cerebral, renal and cardiac tissues obtained from patients with tuberous sclerosis and from control patients. Tuberin immunoreactivity was moderate to strong in neurons and reactive astrocytes of control brains, but was reduced in brains with tuberous sclerosis. Staining intensity of abnormal giant cells varied from negative to moderate in cortical tubers, subependymal nodules and subependymal giant cell astrocytomas. In control kidneys, uriniferous and collecting tubules showed positive immunoreactivity, whereas a focal decrease in their staining intensity was noted in kidneys with tuberous sclerosis. Renal angiomyolipomas were negative for tuberin. In the heart, cardiac muscles in both control and tuberous sclerosis patients were strongly immunoreactive. Cardiac rhabdomyomas in the latter were stained less intensely. These results provide histological evidence for the loss of tuberin in tuberous sclerosis tissues, which is associated with the development of hamartomas in an organ-specific manner.

Adolescent↗

PubMed1997

Developmental changes of glutamate receptors in the rat cerebral cortex and hippocampus.

We studied the immunohistochemical localization of the glutamate receptors (GluR-1, -2, and -3,) in the developing rat cerebral cortex and hippocampus using antibodies to GluR1 and to an epitope common to GluR2 and GluR3 (GluR2/3) subunits. In the cerebral cortex, GluR1 immunoreactivity appeared in the neurons from postnatal day (PND) 0, increased with maturation, was highest at PND 10, decreased until PND 30, and thereafter remained at the same level as on PND 0. GluR2/3 immunoreactivity appeared earlier in scattered neurons on embryonal day (ED) 18, increased with maturation and reached a peak between PND 10 and PND 15, after which the immunoreactivity gradually decreased and reached a plateau at PND 30. For both GluR1 and GluR2/3, some of the pyramidal neurons showed intense staining. In the pyramidal layers of the hippocampus, GluR1 and GluR2/3 immunoreactivity was found in all the pyramidal neurons of the CA1-4 area from ED 20. In the dentate gyrus of the hippocampus, GluR1 and GluR2/3 immunoreactivity was found in the neurons of the granule cells after PND 0. Immunoreactivity in the neurons of the subiculum was found after PND 5 and that of the polymorphic cell layers was found after PND 15-20. Our results indicate that the development of glutamate receptor subunits in the rat cerebral cortex and hippocampus is expressed in different spatial patterns and distinct temporal patterns throughout development and is scheduled during the early postnatal period, when synaptic plasticity or synaptic connection occurs in these regions.

Animals↗

PubMed1997

A comparison of hepatic cytochrome P450 protein expression between infancy and postinfancy.

We immunochemically measured the contents of 9 different cytochrome P450 (CYP) isoenzymes expressed in the liver and compared them between two groups: one group of 6 infant and 4 perinatal patients and one group of 10 patients after infancy (over 1 year old). CYP protein expressed in human liver can be divided into three groups on the basis of expression pattern: (a) CYP2A6, 2C9, 2D6, 2E1, and 3A were present in all samples and no difference was observed between the two groups; (b) CYP1A2, 2B6, and 2C8 were expressed more after infancy than during infancy; and (c) CYP3A7, which has been considered a major CYP enzyme in fetal liver microsomes, was expressed in all infants as well as the four perinatal patients, whereas it was detected in only 2 patients after infancy. These results implied that CYP2A6, 2C9, 2D6, 2E1, and 3A are already expressed during perinatal and infant period, while CYP1A2, 2B6, and 2C8 are expressed highly in subjects over 1 year old, and CYP3A7 disappeared after infancy.

Adolescent↗

PubMed1997

Neuropathological findings in the cerebro-oculo-facio-skeletal (Pena-Shokeir II) syndrome.

An autopsy case is described of an infant with cerebro-oculo-facio-skeletal (COFS) (Pena-Shokeir II) syndrome who died of pneumonia at the age of 5 months, and the pathology of the CNS in this case and the cases in literature were reviewed. Neuropathological examination revealed a partial defect of the corpus callosum, lobulation of the caudate nucleus and putamen, polymicrogyria in the parietal lobes and neuronal heterotopia in the cerebral and cerebellar white matter. The migration disorders suggest that the onset starts in the early fetal period.

Agenesis of Corpus Callosum↗

PubMed1997

Neuronal maturation and N-acetyl-L-aspartic acid development in human fetal and child brains.

The developmental changes in N-acetyl-L-aspartic acid (NAA) were assessed in human fetal and child brains by means of high resolution proton magnetic resonance spectroscopy (MRS). NAA was detected in the cerebral cortex and white matter of fetuses of 16 weeks' gestation. NAA increased gradually from 24 weeks' gestation and remarkably from 40 weeks' gestation to 1 year of age. The developmental changes in tissue NAA in postnatal brains were found to be similar to those of NAA/Cr on clinical proton MRS. As the neuronal cell density in the cerebral cortex decreases with dendritic maturation, an increase in NAA with age may reflect the normal and abnormal development of axons, dendrites and synapses as well as neuronal soma.

Adolescent↗

PubMed1997

A developmental expression of AMPA-selective glutamate receptor subunits in human basal ganglia.

The development of AMPA-selective glutamate receptors (GluR1 and GluR2-3) in human basal ganglia (BG) was investigated in 23 normal brains by means of an immunohistochemical method. Immunoreactivity to GluR1 and 2-3 was detected in the cytoplasm and dendrites of small and large neurons in the BG. GluR2-3 immunoreactivity-positive neurons were clearly observed at 23-24 gestational weeks (GW) in the globus pallidus and at 32 GW in the neostriatum, and reached a peak at 32 GW and 39 GW, respectively. GluR2-3 positive neurons in the BG began to decrease at 1-4 months of age, reaching the low level of adults by 7 months of age. The developmental pattern of GluR1 was similar to that of GluR2-3 in the BG, but the immunoreactivity to GluR1 was a little weaker than that of GluR2-3 in the neostriatum. Furthermore, GluR1 and 2-3 subunit Western blotting confirmed the specificity of the immunohistochemistry. Our results suggest that the development of GluR1 and 2-3 in the BG is consistent with neuronal development in the BG, which supports further that GluR1 and 2-3 play an important role in neuronal differentiation and maturation of the BG.

Adolescent↗

PubMed1997

Early detection of axonal and neuronal lesions in prenatal-onset periventricular leukomalacia.

The expression of beta-amyloid precursor protein (beta-APP) immunoreactivity was investigated in 16 cases of prenatal-onset periventricular leukomalacia (PVL). beta-APP positive axons were found in the early stage of prenatal PVL, which included coagulation necrosis, microglial activation, axonal swelling or astrogliosis, but were not detectable in the late stage of prenatal PVL. Furthermore, beta-APP immunoreactive neurons were also observed in the fifth layer of pyramidal neurons of the cerebral cortex, corresponding to the beta-APP positive axons in PVL. Thus, beta-APP is detected as an early sign of axonal and neuronal lesions in prenatal-onset PVL, and neuronal beta-APP in the cerebral cortex may function to repair cell damage. In addition, prenatal PVL occurred at various stages before birth.

Amyloid beta-Protein Precursor↗

PubMed1997

Immunohistochemical study of microtubule-associated protein 5 (MAP5) expression in the developing human brain.

The expression of microtubule-associated protein 5 (MAP5) in the developing human brain was studied by means of an immunohistochemical method. In the cerebellum, MAP5 immunoreactivity appeared in the molecular layer and subcortical white matter from the early fetal age of 13 gestational weeks (GW), and temporally increased in the outer halves of the molecular layer and subcortical white matter at 36 GW to 2 months of age and 20 to 22 GW, respectively. In the cerebrum, it already appeared in the molecular layer and subcortical white matter from 13 GW, and was marked at 20 to 26 GW and 24 to 32 GW, respectively. Cortical pyramidal neurons gradually became immunoreactive from 28 GW to adolescence. Ependymal cilia were markedly positive in ventricular wall in all ages. In Western blot analyses, MAP5 showed two separate molecular weight bands. In the fetal period 320 kDa protein was prominent, but 300 kDa protein could be detected only at 11 years of age. Thus MAP5 was markedly expressed in growing axon in the fetal period and may be essential for the elongation and maturation as well as the function maintenance of axons and dendrites in developing human brain.

Adolescent↗

PubMed1997

Peroxisomal bifunctional enzyme deficiency: serial neurophysiological examinations of a case.

We report on a case of 21-month-old girl with peroxisomal bifunctional enzyme deficiency, which was diagnosed by means of complementation analysis. Serial neurophysiological examinations were also carried out. The motor and sensory nerve conduction velocities of the median nerve showed lower borderline values at 3 months of age and were within range at 11 months of age. Later, those velocities gradually decreased. The electrically elicited blink reflex at 3 months of age showed the prolongation of latencies of R1, R2 and R2' and the interpeak latencies of R1-R2 and R1-R2'. Furthermore, R1, R2 and R2' showed prolonged latencies at 11 months of age and were absent at 15 months of age. The auditory brainstem response (ABR) showed, bilaterally, normal latency of wave I, prolonged interpeak latencies of waves I-V. At 11 months of age, waves III and IV-V of ABR were detected, but their amplitude was very low. At the age of 15 months ABR was absent. These results and the following report are valuable for understanding the pathogenesis of neurological symptoms.

3-Hydroxyacyl CoA Dehydrogenases↗

PubMed1997

Developmental and aging changes in the expression of amyloid precursor protein in Down syndrome brains.

We studied immunohistochemically the expression of beta-amyloid precursor protein (APP) in the frontal lobes of 18 Down syndrome (DS) patients (20 gestation weeks (GW) to 50 years) and 15 controls (17 GW to 50 years) using six purified antibodies against the secretory forms (N-terminal, N-Amy and Amy540), the Kunitz-type protease inhibitor (KPI) domain, residues 1-28 of beta protein (Affi28), and the carboxyl-terminal fragment (Ac) of APP. In the cortex of fetuses, neonates and infants, immunoreactivity for N-Amy and Ac was observed in both neurons and glial cells, and that for Affi28 in glial cells in the subpial layer in both DS patients and controls suggesting the functioning role of APP was a growth factor. This immunoreactivity disappeared in childhood and reappeared in adulthood in only DS patients. The earlier reappearance of those in DS patients from a young adult age than in normal controls may result from a gene dosage effect, since APP is encoded on chromosome 21. The N-Amy, Amy540, Affi28 and Ac immunoreactivity in glial cells in the developing white matter in the both DS patients and controls may be associated with myelination glia. Immunoreactivity for KPI was noted on the tunica media of the arteries from the neonatal period to adulthood in only DS patients. In senile plaques in DS patients, N-terminal and Affi28 immunoreactivity became detectable at the age of 32 years. N-terminal immunoreactivity in the senile plaques was noted along the periphery of the senile plaques, while that for Affi28 was around the amyloid core. Thus, each fragment of APP exhibited a different localization and time course of immunohistochemical expression. The results indicated that APP plays a role in neuronal development and that its earlier reappearance in adult DS patients is associated with the regeneration process related to aging.

Adolescent↗

PubMed1997

Differential development of the human cerebellar vermis: immunohistochemical and morphometrical evaluation.

Differential development of regions of the human cerebellar vermis was evaluated immunohistochemically and morphometrically between 18 weeks of gestation and 10 years of age. The density of Purkinje cells in the cerebellar vermis decreased rapidly until 38 weeks of gestation and slowly thereafter. At all stages of development, the density was higher in the posterior (lobules VI-IX) than the anterior vermis (lobules I-V). The area of cut sections of the anterior and posterior vermis in the mid-sagittal section increased rapidly before 40 weeks of gestation and gradually after birth, whereas growth was slower in the nodules. These developmental characteristics may be related to the selective susceptibility of cerebellar regions to environmental insults.

Cell Count↗

PubMed1997

Warthin's tumor of the parotid gland with extension into the parapharyngeal space.

A case of Warthin's tumor of the parotid gland which extensively extended into the parapharyngeal space is presented. The tumor border against the parotid gland was ill-defined but the border towards the parapharyngeal structures was clear. Solid portions of the tumor appeared hypointense relative to the gland on both unenhanced T1- and T2-weighted MR images without fat suppression, whereas cystic portions appeared hypointense on T2-weighted images and hyperintense on unenhanced T1-weighted images. Pathologic study showed that the ill-defined margin was caused by inflammation and cystic material consisted of highly proteinaceous material. We concluded that the atypical extension into the parapharyngeal space of the tumor was caused by its location in the deep lobe of the parotid gland and its bulky size.

Adenolymphoma↗

PubMed1997

Assessment of parotid masses: which MR pulse sequences are optimal?

The objective of this paper is to determine which MR pulse sequences are optimal for delineation of lesion and predicting pathologic nature of lesion with signal intensity. A prospective study was performed in 53 parotid masses (39 benign and 14 malignant lesions) in 53 patients. Signal intensity of lesion was visually assessed and lesion/parotid contrast-to-noise ratios were measured. On visual assessment, detection sensitivity was 100% for nonenhanced nonfat-suppressed T1-weighted images, 91% for nonfat-suppressed fast spin-echo (FSE) T2-weighted images, 83% for gadolinium-enhanced fat-suppressed T1-weighted images, and 75% for fat-suppressed FSE T2-weighted images. The highest contrast-to-noise ratios were obtained with nonenhanced T1-weighted images. Hypointensity of lesion relative to the parotid gland on nonfat-suppressed FSE T2-weighted images was seen in 11 of 14 malignancies, 12 of 15 Warthin tumors, and two of 18 pleomorphic adenomas. Cystic portion of hyperintensity on nonenhanced T1-weighted images was solely seen in benign tumors (n = 11). Thus, the highest accuracy (81%) (79% sensitivity and 82% specificity) for predicting malignancy was obtained with a criterion of hypointensity on nonfat-suppressed FSE T2-weighted images plus absence of cystic portion of hyperintensity on nonenhanced T1-weighted images. Nonenhanced T1-weighted images combined with nonfat-suppressed FSE T2-weighted images is optimal for delineation of lesion and prediction of pathologic nature of parotid masses.

Adolescent↗

PubMed1997

Expression of the LIS-1 gene product in brain anomalies with a migration disorder.

Miller-Dieker syndrome (MDS) is a prototype of brain malformations characterized by abnormal neuronal migration. To clarify the pathomechanisms underlying these anomalies, we performed immunohistochemical studies using specific antibodies against the protein product of LIS-1, the candidate gene responsible for the MDS phenotype. The LIS-1 protein was present abundantly and ubiquitously in normally developing brains. Loss of LIS-1 immunoreactivity was observed in brains with MDS, but not in brains with other malformations, such as isolated lissencephaly, holoprosencephaly, Fukuyama-type congenital muscular dystrophy, and Zellweger syndrome. These results suggest that the pathomechanism underlying abnormal neuronal migration in MDS may be specific to this particular type of malformation.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

PubMed1997

Immunohistochemical expression of cell adhesion molecule L1 in hemimegalencephaly.

We demonstrated immunohistochemically an abnormal expression of the neural cell adhesion molecule L1 in 10 developing brains of children with hemimegalencephaly (HM) aged from 36 weeks gestation to 10 years of age, comparing them with 23 controls aged from 13 weeks of gestation to 14 years. There was dense L1 expression in focal regions of the molecular layer beneath leptomeningeal glioneuronal heterotopia, in areas of cerebral cortex with large neurons, and in the disorganized or neuronal heterotopic sites in the white matter in HM. L1 was also heterogeneously enhanced in the abnormal cortex after 1 year of age, suggesting that axonal growth was delayed. These changes persisted into the older age group in the abnormal areas of cortex in HM. The cell bodies of many enlarged neurons in HM were immunopositive for L1, whereas L1 was usually localized to the processes of normal neurons. The delayed L1 immunoreactivity and enlarged L1-immunopositive neurons may be closely related to the pathogenesis of unilateral megalencephaly with cortical dysplasia and heterotopia.

Adolescent↗

PubMed1997

Cu, Zn-superoxide dismutase reaction in neonatal pontosubicular neuron necrosis.

The immunohistochemical localization and changes in copper/zinc superoxide dismutase (Cu, Zn-SOD) were examined in 14 neonates with pontosubicular neuron necrosis (PSN), as compared with those in 15 controls in which the cytoplasm of neurons and glial cells showed SOD immunoreactivity. In the temporal lobes and hippocampus with PSN, Cu, Zn-SOD reactivity was negative in neurons at 0 and 1 days after birth, but was positive after 5 days of age in 8 of 10 cases. In the pons and cerebellum, SOD-positive neurons appeared soon after birth, but eosinophilic or karyorrhectic neurons were SOD negative. On the other hand, glial cells were positive after birth in all cases of PSN, and their reactivity was increased in the cases of reactive astrogliosis. Early loss of the scavenging system directed at free radicals may lead to neuronal damage, and the induction of Cu, Zn-SOD may act as a defense mechanism against damage of neurons in neonates with PSN. Therefore, oxygen-derived free radicals may be one of the pathogenetic factors of PSN with characteristics of apoptosis in neonates.

Case-Control Studies↗

PubMed1997

Evidence of abnormal differentiation in giant cells of tuberous sclerosis.

To characterize the giant cells in tuberous sclerosis, we examined immunoreactivity for nestin, vimentin, microtubule-associated protein 1B (MAP1B), MAP2, neurofilament, and glial fibrillary acidic protein (GFAP) in cortical tubers detected in brain specimens from 6 patients with tuberous sclerosis who had undergone surgical resection for treatment of intractable epilepsy. Giant cells with a neuronal appearance, "neuron-like giant cells," had a round centrally-placed nucleus with a single, prominent nucleolus, and Nissl substance was commonly present in cortex. These neuron-like giant cells demonstrated consistently strong immunoreactivity for neurofilament and MAP1B and occasional immunopositivity for nestin and vimentin and were rarely positive for GFAP. "Indeterminate giant cells," characterized by abundant cytoplasm, an absence of Nissl substance, and one or more eccentric nuclei, demonstrated consistent immunoreactivity for nestin, vimentin, and MAP1B and were rarely positive for neurofilament, but more than half displayed immunoreactivity for GFAP. These observations suggest that the indeterminate giant cells exhibit limited neuronal and inconsistent astroglial characteristics, implying aberrant cellular differentiation in tuberous sclerosis.

Cell Differentiation↗

PubMed1997

Characteristic neuropathology of leukomalacia in extremely low birth weight infants.

Extremely low birth weight (ELBW) infants with periventricular leukomalacia (PVL) were examined by neuropathological and immunohistochemical methods. Thirteen ELBW infants of 85 infants with PVL, born at 23 to 27 weeks of gestation, showed a widespread type of distribution of PVL from the deep to intermediate white matter. Immunohistochemistry demonstrated glial fibrillary acidic protein (GFAP)-positive astrocytes to be increased in the deep white matter, often spreading to the intermediate white matter, in all cases of PVL. Tumor necrosis factor-alpha (TNF-alpha)-positive cells were found in the deep to intermediate white matter in 69% of PVL cases and appeared earlier, from 23 weeks of gestation, than in controls. beta-Amyloid precursor protein (beta APP)-positive axons were found around PVL in the deep to intermediate white matter in 85% of the cases. In age-matched control ELBW infants, GFAP-, TNF-alpha-, or beta APP-positive cells were never found. Therefore, in ELBW infants, widespread axonal damage and glial activation with cytokine production occur in the progression in characteristic PVL lesions.

Amyloid beta-Protein Precursor↗