Biomedical subjects

David T Yew

Publications and source records attributed to David T Yew.

30 records · Page 2Linked to original sources

PubMed2004

Fas and activated caspase 8 in normal, Alzheimer and multiple infarct brains.

Using immunohistochemistry, Fas and caspase 8 positive sites were localized in the brains of Alzheimer patients and those with multiple infarcts as well as age-matched normal. The frontal, occipital and hippocampal regions were dissected out from these patients and normal individuals shortly after death. Positive Fas neurons were found in all these regions of normal individuals and Alzheimer patients, but not in the brains of patients with multiple infarct. Activated caspase 8 protein was found only in the brains of Alzheimer patients and not in the other groups. Plaques in the Alzheimer patients were positive for Fas and activated caspase 8. The former was localized in the membrane and the inside of the plaque whereas activated caspase 8 was only present in the interior of the plaque, as revealed by confocal microscopy. Our study shows that caspase 8 was activated in the Alzheimer brain and the presence of Fas and activated caspase 8 points to a possibility that at least some plaques were of intracellular origin as Fas was a cell membrane receptor and caspase 8 was a intracellular enzyme downstream to Fas. Furthermore, we had confirmed that in most neurons Fas and caspase 8 did not exist concomitantly and that the glial cells (astrocytes) did not express caspase 8 in Alzheimer patients.

Aged↗

PubMed2004

Age-related alterations in cytochrome c-mediated caspase activation in rhesus macaque monkey (Macaca mulatta) brains.

Age-related changes and regional differences in caspase expression were determined in the primate brain. Using immunoblot analysis, the levels of endogenous caspase-3, caspase-9 and cytochrome c-triggered activated caspase-3 were examined in brain homogenates from the prefrontal, motor and visual cortices, cerebellum, hippocampus and amygdala of 4-year-old and 20-year-old rhesus macaques. Procaspase-3 was detected in similar quantities in all brain regions of both young and aging macaques. Being found in all brain regions, caspase-9 was significantly elevated in old macaques as compared to young ones. After incubation with cytochrome c, active forms of caspase-3 were detected in all brain regions of young and old macaques. In almost all brain regions of old monkeys, the levels of cytochrome c-dependent caspase-3 activation were higher than those of young macaques. These results suggest that the aging rhesus macaque brain has a lower threshold to apoptotic stimuli.

Adenosine Triphosphate↗

PubMed2004

The complexity of the visual cells and visual pathways of the sturgeon.

The visual cells in the retinae of the sturgeon were studied by scanning electron microscopy and transmission electron microscopy. Our investigations revealed the presence of rods, two types of single cones, one type of double cone (two nonidentical cone components adhered together), and one type of twin cone (two identical cone components adhered together). In some of the cones, large glycogen bodies were present in the inner segments and all cones contained oil droplets. Such cone morphology was very similar to that described in the retinae of higher vertebrates, for example the chicken. DiI tracing of retinofugal pathways following uniocular injection demonstrated their bilateral localization and extensive termination in the diencephalon and mesencephalon of both sides. Fibers also crossed over from one side to another through commissures, including the posterior commissure. The complexity of the pathway surpassed that of the teleosts and further indicated the evolutionary importance of this fish.

Animals↗

PubMed2004

Distribution of neuropeptide Y-immunoreactive neurons in the human brainstem, cerebellum, and cortex during development.

1. Neuropeptide Y is found throughout the central nervous system where it appears to play a wide range of often poorly understood functions. In this study, the distribution of neuropeptide Y immunoreactive (NPY-ir) neurons in the brainstem, cerebellum, and cerebral cortex of human fetuses ranging in age from 11 gestational weeks to term was investigated by immunohistochemistry. 2. The NPY-ir cells were detected in the dorsal and ventral rostral midbrain and the interpeduncular nucleus by 21 weeks and 32 weeks of gestation, respectively. Although no positive cells were found in the pons, the NPY-ir fibers were detected there at 32 gestational weeks. 3. The vagal, hypoglossal, and olivary nuclei of the medulla oblongata contained immunoreactive cells by week 21 and the medullary reticular formation by week 25 of gestation. In most of these locations, both the number and size of neuropeptide Y positive cells were greater at birth and reached maximal values of 100-400 cells per 1 mm2 and 2-5 microm in diameter, respectively. 4. In the cerebellum, numerous NPY-ir horizontal and granule cells, as well as the cells within the dentate nucleus were observed as early as 21 weeks of gestation. 5. The NPY-ir cells were also detected in the developing cerebral cortex, with the earliest activity observed within the temporal cortex at 14 weeks of gestation. By week 21, positive cells appeared in the visual, frontal, sensory, and motor cortices. Most of these cells were bipolar or multipolar in morphology but their numbers at birth were relatively low. 6. Our results show a wide distribution of the NPY-ir cells in the developing human brain and offer supporting evidence for the important modulatory role of NPY in both the fetus and adult.

Brain Stem↗

PubMed2003

Development of catecholaminergic neurons in the human medulla oblongata.

Distribution and maturation of catecholaminergic (CA) neurons have been studied by tyrosine hydroxylase immunohistochemistry in the medulla oblongata of human fetuses aged 14.5-25 weeks of gestation. Already at 14.5 weeks, CA neurons were observed in two longitudinally oriented cell clusters, one located ventrolaterally in the area of the lateral reticular and ambiguous nuclei, the other one dorsomedially forming 4 groups related to the dorsal vagal nucleus, the commissural nucleus of the vagus, the nucleus of the tractus solitarius and the area postrema. CA neurons in the area postrema were often found close to blood vessels. Scattered intermediate CA neurons were seen between these two larger clusters. CA neurons still appeared immature exhibiting bipolar morphology with only one or two short stout processes, which hardly branched. At 21 weeks, CA neurons occupied essentially the same location, but had a more mature morphology. Though still bipolar in shape, they had thinner and much longer processes which frequently branched. Both in the ventrolateral and the dorsomedial cell clusters, these processes were frequently lying close to blood vessels. At 25 weeks, CA cells had matured into multipolar neurons with long thin processes forming fine fiber networks in the ventrolateral medulla as well as around and within the dorsal vagal and solitarius nuclei. Only at this stage, a distinct CA fiber tract was seen located in the region of the tractus solitarius. Our results indicate that CA neurons in the human medulla, which are presumably involved in the control of ventilation and blood pressure, though generated rather early during development, mature relatively late.

Adult↗

PubMed2003

Differential expression of S100 proteins in the developing human hippocampus and temporal cortex.

S100 calcium binding proteins have long been known to express in the adult nervous system, but their distribution in the developing brain, especially the human fetal brain, is largely unknown. We used an immunohistochemical method to determine the expression of three S100 proteins, namely S100A4, S100A5, and S100A13, in the human fetal hippocampus and temporal cortex from 12 to 33 weeks of gestation. At 12 weeks, S100A5 was strongly expressed in the cells and fibers of the polymorphic, pyramidal, and molecular layers of the hippocampus. Thereafter, its expression decreased with age. In the temporal cortex, S100A5 expression was detected from 12 weeks onwards, peaked at 20 to 24 weeks, and then decreased with age. The horizontal fibers of the marginal zone were immunoreactive at all stages examined. S100A13 immunoreactivity was also detected in both cells and fibers of the hippocampus at 12 weeks, became slightly stronger at 20 weeks, and then decreased with age. In the temporal cortex, S100A13 immunoreactivity was also strong in all cellular layers at 12 to 24 weeks before it declined with age from 28 weeks onwards. Among the three proteins examined, S100A4 showed the weakest expression, which was detected in the cells and fibers of the hippocampus and the temporal cortex at all stages examined. Our results have demonstrated for the first time, in the human fetal hippocampus and temporal cortex, specific spatio-temporal patterns of expression of these proteins, all of which are likely to have different roles to play during development despite their pronounced sequence homology.

Fetus↗

PubMed2003

Development of the human cerebral cortex: a histochemical study.

In recent years, improvement in diagnostic techniques has led to better recognition of "disorders of cortical development". These disorders constitute a significant cause of epilepsy, mental retardation, developmental delay and neurological deficits in childhood, and may also contribute to the pathogenesis of psychological and neurodegenerative diseases in adults. Hitherto, however, few systematic studies of the human fetal cortex have been performed, and little is known about the ontogenetic processes of the neocortex in man. The aim of the study is to establish an understanding of the developmental events that occur in the second and third trimesters of gestation, by investigating the biochemical patterns of development of the human neocortex during this period. The temporal and spatial patterns of expression of the neuronal markers gamma-aminobutyric acid (GABA), choline acetyltransferase (ChAT), dopamine beta hydroxylase (DBH), dopamine receptor DR1 and synaptophysin, as well as the glial cell markers glial fibrillary acidic protein (GFAP), S100B and excitatory amino acid transporter protein GLT-1 are delineated in the fetal cortex using immunohistochemistry. Results of this study showed that different neuronal and glial cell proteins follow different developmental patterns and many show inter- or intra-regional variations in expression. Details of these patterns are described and discussed. The early expression of these proteins suggests that they play important roles in the developmental processes of cell proliferation, migration and differentiation. Both neurotransmitters and glial cell proteins probably function outside the confines of synapses in the fetal brain, as paracrine/autocrine factors. Early developmental events seem to be dictated by an innate programme, whereas late events may be more susceptible to extrinsic influences. It is hoped that knowledge of the normal developmental process can lead to better understanding of the causes and mechanisms of "disorders of cortical development", and to better treatments.

Acetylcholine↗

PubMed2002

Proliferation and apoptosis in the developing human neocortex.

The cell kinetics of the developing central nervous system (CNS) is determined by both proliferation and apoptosis. In the human neocortex at week 6 of gestation, proliferation is confined to the ventricular zone, where mitotic figures and nuclear immunoreactivity for proliferating cell nuclear antigen (PCNA) are detectable. Cell division is symmetric, with both daughter cells reentering mitosis. At week 7, the subventricular zone, a secondary proliferative zone, appears. It mainly gives rise to local circuit neurons and glial cells. Around week 12, the ventricular and subventricular zones are thickest, and the nuclear PCNA label is strongest, indicating that proliferation peaks at this stage. Thereafter, asymmetric division becomes the predominant mode of proliferation, with one daughter cell reentering mitosis and the other one migrating out. Towards late gestation, the ventricular and subventricular zones almost completely disappear and proliferation shifts towards the intermediate and subplate zones, where mainly glial cells are generated. A remnant of the subventricular zone with proliferative activity persists into adulthood. In general, proliferation follows a latero-medial gradient in the neocortex lasting longer in its lateral parts. Apoptotic nuclei have been detected around week 5, occurring in low numbers in the ventricular zone at this stage. Apoptotic cell death increases around midgestation and then spreads throughout all cortical layers, with most dying cells located in the ventricular and subventricular zones. This spatial distribution of apoptosis extends into late gestation. During the early postnatal period, most apoptotic cells are still located in the subcortical layers. During early embryonic development, proliferation and apoptosis are closely related, and are probably regulated by common regulators. In the late fetal and early postnatal periods, when proliferation has considerably declined in all cortical layers, apoptosis may occur in neurons whose sprouting axons do not find their targets.

Apoptosis↗

PubMed2002

A cytological study on the development of the different types of visual cells in the chicken (Gallus domesticus).

The formation of visual cells and their intracellular organelles was studied in the embryonic chicken (Gallus domesticus) between stage 36 and hatching. Cilia formation was observed at stage 30 and by stage 42, outer segment formation from the cilia was evident. The inner segments appeared as buddings at stage 36. By stage 37, the buddings of double cones were observed clearly and such buddings elongated by stage 42. Both the single cones and rods appeared as buddings by stage 38 and elongation of the buddings was seen by stage 42. Oil droplets initially appeared by stage 39 in accessory cones and were observed in other cones by stage 42. Glycogen bodies were demonstrated firstly in rods and accessory cones at stage 43 and their development was completed by stage 45. In essence, all the essential elements of the visual cells were fully developed by hatching.

Aging↗

PubMed2002

Novel identification of the different types of cones in the retina of the chicken.

1. Although single cones and double cones in the chicken retina had been documented for more than 30 years, the exact morphology of these cells had never been studied by the scanning electronmicroscopy. In this brief report, we present the evidence for the first time the existence of two types of single cones and three types of double cones (termed as types A, B. and C), each with distinct morphology. 2. The proportion of type A:type B:type C double cones, as estimated from the midperipheral and central regions of our scanning specimens, was about 30%:50%:20%. 3. Based on the literature data that red oil droplets reside in single cones and yellow oil droplets in chief cones of the double cones, the proportion of single to double cones was deciphered and the relative proportion was estimated to be 1:0.91 in the central region, 1:0.92 in the midperiphery, and 1:0.84 in the periphery.

Animals↗

PubMed2002

Pien Tze Huang protects the liver against carbon tetrachloride-induced damage.

Pien Tze Huang, a traditional Chinese medicine, has been extensively used as a therapeutic drug in the treatment of liver diseases. In this study, we have examined its ability to protect the liver from carbon tetrachloride (CCl4)-induced damage in the mouse. Histological observations revealed that CCl4 treatment induced extensive degenerative changes in the hepatocytes surrounding the central veins of the liver. However, these changes were much reduced by more than 28% in mice fed with 0.5 mg of Pien Tze Huang/g body weight/dose (3 doses over 36 hr) prior to CCl4 treatment. The effects of Pien Tze Huang were then further investigated in a hepatoma cell line. Flow analysis showed that it had no significant effects on cell proliferation. When the ability of Pien Tze Huang to influence various response elements of important signal transduction pathways was examined in the hepatoma cell line, it was found that Pien Tze Huang stimulated an increase in the response of AP1, CRE and NFkappaB responsive elements. The transcriptional factors of these responsive elements are known to play important roles in regulating cell death and survival. We thus postulate that the ability of Pien Tze Huang to protect the liver from damage is attained through its ability to modulate the activity of these important signal transduction pathways.

Animals↗

PubMedDate not supplied

Three-dimensional reconstruction of brain surface anatomy based on magnetic resonance imaging diffusion-weighted imaging: a new approach.

Fifty normal noninfarct patients and 12 cases with infarcts of the cerebrum were examined with routine magnetic resonance imaging and echo-planar diffusion-weighted imaging. The diffusion-weighted three-dimensional images were reconstructed with volume-rendering processing on workstation. Precentral gyrus, postcentral gyrus, superior parietal lobule, superior frontal gyrus, precentral sulcus, central sulcus, postcentral sulcus, intraparietal sulcus and superior frontal sulcus were best shown of all structures with an arbitrary score of 2.61-2.77. Supramarginal gyrus, middle frontal gyrus, inferior frontal gyrus and lateral sulcus were clearly shown in the majority of the cerebra with average scores of 2.0-2.49; angular gyrus, inferior frontal sulcus and superior temporal gyrus were not demonstrated satisfactorily and their average scores were 1.67-1.89. Middle temporal gyrus, inferior temporal gyrus, superior temporal sulcus and inferior temporal sulcus were difficult to identify, and thus had average scores of 0.87-1.26. Brain surface structures were better displayed in the older group of individuals than in the younger group. The structures in the 12 cases with acute or chronic cerebrum infarcts were also satisfactorily demonstrated with this new technique.

Aged↗