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Biomedical subjects

T Wei

Publications and source records attributed to T Wei.

At least 19 recordsLinked to original sources
PubMed2002

Chemokine expression in the central nervous system of mice with a viral disease resembling multiple sclerosis: roles of CD4+ and CD8+ T cells and viral persistence.

During the first 45 days after intracerebral infection with Theiler's murine encephalomyelitis virus (TMEV), the levels of mRNAs encoding chemokines MCP-1/CCL2, RANTES/CCL5, and IP-10/CXCL10 in the central nervous system (CNS) are closely related to the sites of virus gene expression and tissue inflammation. In the present study, these chemokines were monitored during the latter 135 days of a 6-month course of TMEV-induced disease in susceptible (PLJ) or resistant (C57BL/6) mice that possessed or lacked either CD4+ or CD8+ T cells. These data were additionally correlated to mouse genotype, virus persistence in the CNS, antiviral antibody titers, mortality, and the severity of neurological disease. Surprisingly, the major determinant of chemokine expression was virus persistence: the factors of susceptible or resistant genotype, severity of neuropathology, and presence or absence of regulatory T cells exerted minimal effects. Our observations indicated that chemokine expression in the CNS in this chronic viral disorder was intrinsic to the CNS innate immune response to infection and was not governed by elements of the adaptive immune system.

Animals↗
PubMed2001

P2X7-like receptor activation in astrocytes increases chemokine monocyte chemoattractant protein-1 expression via mitogen-activated protein kinase.

Leukocyte infiltration in the CNS after trauma or inflammation is triggered in part by upregulation of the chemokine, monocyte chemoattractant protein-1 (MCP-1), in astrocytes. However the signals that induce the upregulation of MCP-1 in astrocytes are unknown. We have investigated the roles for ATP P2X7 receptor activation because ATP is an intercellular signaling transmitter that is released in both trauma and inflammation and P2X7 receptors are involved in immune system signaling. Astrocytes in primary cell culture and acutely isolated from the hippocampus were immunopositive for P2X7 receptors. In astrocyte cultures, application of the selective P2X7 agonist, benzoyl-benzoyl ATP (Bz-ATP), activated MAP kinases extracellular signal receptor-activated kinase 1 (ERK1), ERK2, and p38. Purinergic antagonists depressed this activation with a profile suggesting P2X7 receptors. Bz-ATP also increased MCP-1 expression in cultured astrocytes, and again P2X7 antagonists prevented this increase. Blocking either the ERK1/ERK2 or the p38 pathway (with PD98059 or SB203580, respectively) significantly inhibited Bz-ATP-induced MCP-1 expression. Coapplication of both antagonists caused a greater depression. We also tested the roles for ATP receptor activation in inducing MCP-1 upregulation in corticectomy, an in vivo model of trauma. This model of cortical trauma was previously shown to increase MCP-1 expression in vivo principally in astrocytes. Suramin, a wide-spectrum purinergic receptor antagonist, significantly depressed the rapid (3 hr) trauma-induced increase in MCP-1 mRNA. These data indicate that purinergic transmitter receptors in astrocytes are important in regulating chemokine synthesis. The regulation of MCP-1 in astrocytes by ATP may be important in mediating communication with hematopoietic inflammatory cells.

Adenosine Triphosphate↗
PubMed2001

Temporal lobe volume determined by magnetic resonance imaging in schizotypal personality disorder and schizophrenia.

The volumes of the whole temporal lobe, the superior temporal gyrus and the corpus callosum were measured on magnetic resonance images from 13 patients with schizotypal personality disorder (SPD), 27 patients with schizophrenia, and 31 age- and sex-matched controls. Temporal lobe structures were traced on consecutive 1.2mm thick SPGR images. Both patient groups had smaller temporal lobes than normal volunteers, a difference that was more marked for the area outside the superior temporal gyrus than for the STG. Correcting for brain volume diminished differences between normal subjects and schizophrenia patients, but the differences between normal subjects and SPD patients remained. Normal volunteers and SPD patients showed significant correlations between the sagittal section area of the posterior portion of the corpus callosum, which carries temporal interhemispheric connections, and the white matter volume of the temporal lobe. While the sample size is modest, taken together, these results suggest that the psychopathological symptoms of SPD may be related to temporal gray matter loss with relatively intact white matter connectivity, while the cognitive and psychotic symptoms of schizophrenia may be related to temporal gray loss combined with disruption of normal patterns of white matter development.

Adult↗
PubMed2001

Monocyte chemoattractant protein (MCP)-1 is rapidly expressed by sympathetic ganglion neurons following axonal injury.

EDI-immunoreactive macrophages, absent from the superior cervical ganglia (SCG) of normal rats, appear in these ganglia within 48h after postganglionic axotomy. Further, resident macrophages show changes after axotomy. Since chemokines function as chemoattractants and activators of leukocytes, the effects of axotomy on chemokine expression in the SCG were examined. Within 6 h after nerve transection, increases were seen in mRNA levels for monocyte chemoattractant protein (MCP)-1. MCP-1 mRNA was concentrated in a population of neurons, while MCP-1 protein was localized to endothelial cells. This axotomy-induced neuronal MCP-1 expression may trigger the infiltration and/or activation of macrophages in SCG after injury.

Animals↗
PubMed2001

Tears contain the complement regulator CD59 as well as decay-accelerating factor (DAF).

Previous studies have shown that DAF (or CD55), a cell surface inhibitor of autologous C3 activation, is present in tears and that > 90% of the C3 convertase regulatory activity in tear fluid resides in this protein (Lass JH et al., Invest Ophth Vis Sci 1990; 31:1136-48). This study investigated whether (i) the membrane cofactor protein (MCP or CD46), an additional factor that regulates C3 activation, and (ii) the membrane inhibitor of reactive lysis (MIRL or CD59), a cell surface regulator that acts to prevent formation of the membrane attack complex, are also present in tears, and if so, are functional. Two-site immunoradiometric assays showed that MCP is present in tears at low levels (42 + 8 ng/ml, n = 8) while CD59 is present at levels (222 + 78 ng/ml, n = 14) comparable to those of DAF (325 + 289 ng/ml, n = 12). The concentrations of CD59 (i) were increased two-fold or more in closed eye tears, and (ii) were decreased in reflex tears. Western blotting showed that CD59 protein in tears migrates with an apparent mol. wt similar to membrane CD59 protein. Phenyl-Sepharose adsorption and Triton X-114 partitioning of tear CD59 as well as of tear DAF however, showed that both proteins are devoid of GPI anchors. Assays using cobra venom factor-activated human serum and guinea pig erythrocytes showed that CD59 is functionally active in inhibiting autologous C5b-9-mediated lysis and, under constitutive conditions, accounts for > 85% of the C9 inhibitory activity in tear fluid.

CD55 Antigens↗
PubMed2001

Regulation of monocyte chemoattractant protein (MCP)-1 transcription by interferon-gamma (IFN-gamma) in human astrocytoma cells: postinduction refractory state of the gene, governed by its upstream elements.

Monocyte chemoattractant protein (MCP)-1 is expressed by astrocytes in diverse inflammatory states and is a key regulator of monocyte recruitment to the central nervous system (CNS). In the current study, we addressed mechanisms by which transcription of the human MCP-1 gene (hMCP-1) was terminated, after induction by interferon (IFN)-gamma. Our results demonstrated that IFN-gamma-induced transcription of hMCP-1 was followed by a refractory state, during which hMCP-1 was resistant to restimulation by either IFN-gamma or heterologous activators such as TNF-alpha. This refractory state affected the hMCP-1 gene selectively, as other IFN-gamma-inducible genes remained responsive to restimulation. The IFN-gamma-induced hMCP-1 refractory state was governed at the transcriptional level and was sensitive to protein synthesis inhibitors, suggesting a requirement for newly expressed components. A minimal 213 base pair hMCP-1 regulatory element directed both IFN-gamma-mediated transcription and the subsequent refractory state. We previously demonstrated that IFN-gamma treatment resulted in coordinate protein occupancy in vivo of two hMCP-1 promoter elements, a gamma-activated site (GAS) and a GC-rich element. During the refractory state, IFN-gamma treatment failed to induce protection of either the hMCP-1 GAS element or the GC box. These results furnish insight into the expression of hMCP-1 during CNS inflammation and provide the first delineation of an IFN-gamma-induced transcriptional refractory state.

Astrocytoma↗
PubMed2001

[Relationship between water supply and consumption of main planting tree species of protection forests in loess area of western Shanxi Province].

Based on three years point-fixed observation, this paper analyzed the relationship between water supply and consumption of black locust(Robinia pseudoscacia L.) and Chinese pine(Pinus tabulaeformis Carr.), the main tree species of protection forests in the loess area of the western Shanxi Province. In April, May and June, the water supply was less than water consumption, while in raining season, the water supply was abundant, and the water storage in soil was increased. During dry seasons and years, more water consumption and less available water supply occurred in high-density stand, showing a serious water deficiency. The water deficiency was in order of south-facing slope > semi-south-facing slope > north-facing slope. The study shows that water consumption characters coefficient could be used as an index to indicate the growth pattern of trees, and the relationship between water supply and consumption.

Trees↗
PubMed2000

Nitric oxide induces oxidative stress and apoptosis in neuronal cells.

Within the central nervous system and under normal conditions, nitric oxide (NO) is an important physiological signaling molecule. When produced in large excess, NO also displays neurotoxicity. In our previous report, we have demonstrated that the exposure of neuronal cells to NO donors induced apoptotic cell death, while pretreatment with free radical scavengers L-ascorbic acid 2-[3, 4-dihydro-2,5,7,8-tetramethyl-2-(4,8, 12-trimethyltridecyl)-2H-1-benzopyran-6-yl-hydrogen phosphate] potassium salt (EPC-K1) or superoxide dismutase attenuated apoptosis effectively, suggesting that reactive oxygen species (ROS) may be involved in the cascade of events leading to apoptosis. In the present investigation, we directly studied the kinetic generation of ROS in NO-treated neuronal cells by flow cytometry using 2', 7'-dichloro-fluorescein diacetate and dihydrorhodamine 123 as redox-sensitive fluorescence probes. The results indicated that exposure of cerebellar granule cells to the NO donor S-nitroso-N-acetylpenicillamine (SNAP) induced oxidative stress, which was characterized by the accumulation of cytosolic and mitochondrial ROS, the increase in the extracellular hydrogen peroxide level, and the formation of lipid peroxidation products. SNAP treatment also induced apoptotic cell death as confirmed by the formation of cytosolic mono- and oligonucleosomes. Pretreating cells with the novel antioxidant EPC-K1 effectively prevented oxidative stress induced by SNAP, and attenuated cells from apoptosis.

Animals↗
PubMed2000

Mechanisms of apoptosis in rat cerebellar granule cells induced by hydroxyl radicals and the effects of EGb761 and its constituents.

In this study investigation is made on whether oxidative stress produced by treatment with hydroxyl radicals can induce apoptosis in rat cerebellar granule cells. The protective effects of Ginkgo biloba extract (EGb761) and its active constituents against apoptosis are also examined. The results show that hydroxyl radicals generated by the Fenton reaction induced apoptosis in cerebellar granule cells, which was associated with the decrease in the Bcl-2 mRNA level and the increase in the protein levels of the transcription factors Fos and Jun. Moreover, hydroxyl radicals induced time-dependent lipid peroxidation in cells and caused the changes in the sulfhydryl group binding sites on the membrane proteins. Hydroxyl radicals may induce apoptosis via different signaling pathways. EGb761 attenuated these changes and its different constituents showed different effects. The total flavonoid component of EGb761 and a mixture of flavonoids and terpenes protected cerebellar granule cells from oxidative damage and apoptosis induced by hydroxyl radicals. Total terpenes of EGb761 did not protect against apoptosis. Flavonoids and terpenes did not show a synergistic effect in this regard.

Animals↗
PubMed2000

Shape and size of the corpus callosum in schizophrenia and schizotypal personality disorder.

The size and shape of the corpus callosum were assessed on sagittal section magnetic resonance images in 27 patients with schizophrenia, 13 patients with schizotypal personality disorder (SPD), and 30 healthy volunteers. High-resolution 1.2mm axial SPGR images were acquired and resectioned so that the sagittal plane passed through the anterior and posterior commissures and was parallel to the interhemispheric fissure. The corpus callosum and the whole brain were traced on midsagittal section slices of each brain, and the callosum was divided into 30 anteroposterior sectors. Pixel-by-pixel chi-square and thin-plate spline analyses were used to assess between-group shape differences. Size of the corpus callosum was smaller anteriorly in the genu of the corpus callosum and posteriorly in the splenium in schizophrenic patients than in normal controls. The genu of the corpus callosum was larger in SPD patients than in schizophrenic patients or normal controls. The posterior corpus callosum was largest in normal controls, smaller in SPD patients, and smallest in schizophrenic patients. Shape analysis was consistent with these size comparisons, and suggested a downward bowing of the corpus callosum in schizophrenic and SPD patients. SPD patients also had a region of the callosum just posterior to the genu that was narrower than in the other two groups. The decreases in corpus callosal size in schizophrenia varied directly with length of illness, perhaps indicative of a progressive process. The patient-control differences in callosal size and shape are consistent with a hypothesis of decreased connectivity between the left and the right hemispheres in schizophrenia and SPD.

Adult↗
PubMed2000

Whole-brain diffusion MR histograms differ between MS subtypes.

OBJECTIVE: To determine whether quantitative whole-brain MR diffusion histograms in patients with MS differ from those of normal control subjects. BACKGROUND: MRI detects macroscopic cerebral lesions in MS, but the white matter lesion burden on MRI correlates imperfectly to clinical disability. Previous reports have further suggested abnormalities in white matter of MS patients with no visible lesions on conventional MRI. METHODS: A total of 25 subjects (13 with MS [9 relapsing-remitting, 4 secondary progressive] and 12 healthy control subjects) underwent diffusion-weighted echoplanar MRI encompassing the entire brain. The average apparent diffusion coefficient (ADCave, or diffusion trace) was calculated on a pixel-by-pixel basis after segmentation of intracranial space from calvarium and extracranial soft tissues. Whole-brain ADCave histograms were calculated and plotted for statistical comparison. RESULTS: Mean whole-brain MR ADCave in MS patients was elevated and histograms were shifted to higher values compared with normal control subjects. Mean whole-brain ADCave of secondary progressive patients was shifted to higher values compared with relapsing-remitting patients. Whole-brain ADCave histograms of relapsing-remitting patients showed no significant difference from normal control subjects. CONCLUSION: Whole-brain MR diffusion histograms may quantitate overall cerebral lesion load in patients with MS and may be able to discern differences between clinical subgroups.

Adolescent↗
PubMed2000

Absent or reduced expression of the caspase 8 gene occurs frequently in neuroblastoma, but not commonly in Ewing sarcoma or rhabdomyosarcoma.

PROCEDURE: To clarify whether the caspase 8 gene is involved in the pathogenesis of neuroblastoma (NB), we examined alterations of the caspase 8 gene in 15 NB, seven Ewing sarcoma (ES), and eight rhabdomyosarcoma (RMS) cell lines, using reverse transcription-polymerase chain reaction (RT-PCR) and RT-PCR single-strand conformation polymorphism (SSCP) analyses. RESULTS: The caspase 8 gene was not expressed in 11 (73%) of 15 NB cell lines, it was absent in only one of seven ES cell lines, but was present in all eight RMS cell lines examined. No mutations were detected in any cell lines examined. CONCLUSIONS: Inactivation of the caspase 8 gene is considered to be involved in the pathogenesis of NB, but not ES or RMS.

Caspase 8↗
PubMed2000

Hydrogen peroxide-induced oxidative damage and apoptosis in cerebellar granule cells: protection by Ginkgo biloba extract.

The ability of oxidative stress to induce apoptosis and the protective effects of Ginkgo biloba extract (EGb761) against this induction were studied in cultures of rat cerebellar granule cells. Cells were exposed to oxidative stress by treatment with 50 microm hydrogen peroxide+100 microm ferrous sulphate which generates hydroxyl radicals by Fenton reaction. Both morphological observation and biochemical analysis revealed that H(2)O(2)/FeSO(4)treatment induced apoptotic cell death in cerebellar granule cells, which was characterized by chromatin condensation and DNA fragmentation. During this process, the fluidity of the cell membrane decreased markedly, and the conformation of membrane proteins altered significantly. Pretreating cerebellar granule cells with the antioxidant EGb761 (Ginkgo biloba extract) effectively attenuated oxidative damage induced by H(2)O(2)/FeSO(4), and prevented cells from apoptotic cell death. The results suggested that EGb761 might be used as a potential drug for neuronal diseases associated with the excessive production of reactive oxygen species.

Animals↗
PubMed2000

Unique chromosome identification and sequence-specific structural analysis with short PNA oligomers.

We have extended our earlier work to show that individual 14-20mer peptide nucleic acid probes directed against interspersed alpha-satellite sequences can specifically identify chromosomes. Peptide nucleic acid (PNA) probes were used to detect chromosomal abnormalities and repeat structure in the human genome by fluorescence in situ hybridization (FISH). The hybridization of a single PNA probe species directed against a highly abundant alpha-satellite DNA repeat sequence was sufficient to absolutely identify a chromosome. Selection of highly repetitive or region-specific DNA repeats involved DNA database analysis. Distribution of a specific repeat sequence in human genome was estimated through two means: a computer program "whole genome" approach based on approximately 400 Mb (12%) human genomic sequence. The other method involved directed search for alpha satellite sequences. In total, approximately 240 unique DNA repeat candidates were found. Forty-two PNA probes were designed for screening chromosome-specific probes. Ten chromosome-specific PNA probes for human Chromosomes (Chrs) 1, 2, 7, 9, 11, 17, 18, X, and Y have been identified. Interphase and metaphase results demonstrate that chromosome-specific PNA probes are capable of detecting simple aneuploidies (trisomies) in human. Another set of PNA probes showed distinct banding-like patterns and could be used as sequence-specific stains for chromosome "bar coding". Potential application of PNA probes for investigating repeat structure and function is also discussed.

Base Sequence↗
PubMed2000

Hemispheric asymmetry for selective attention.

A letter-identification task, previously demonstrated to show activation of the pulvinar nucleus of the thalamus with fluodeoxyglucose position emission tomography, was administered to 20 normal volunteers. The letter to be detected could appear alone as a big stimulus or as a small one stimulus surrounded by flanking letters. To test for a hemispheric specialization for filtering processes, the stimuli were displayed horizontally, either in the left or in the right hemifield, or vertically, either above or below the fixation point. In addition, to study the effect of cognitive processes on selective attention resources, we varied the feedback conditions, by delivering or not delivering a blue flash in cases of misses or mistakes. The results show a significant interaction between the type of stimulus (alone or surrounded by flankers) and the hemifield of presentation (left or right) only in the condition where the subjects were presented stimuli horizontally without any feedback. In this condition, reaction times (RTs) were shorter in the left hemifield than in the right hemifield for single stimuli, whereas for stimuli surrounded by flankers, the opposite pattern was observed, that is, shorter RT in the right hemifield than in the left one. The present findings suggest a hemispheric specialization for selective attention, in particular at the subcortical level.

Adult↗
PubMed2000

Visual target detection paradigm for the study of selective attention.

The current protocol can be used to examine selective attention. It has been used to acquire behavioral performance data in neurologically healthy normal control subjects and schizophrenic patients. A modified version, also described here, has been used to acquire functional neuroimaging data in normal subjects using positron emission tomography. Subject response accuracy and reaction times are recorded while subjects detect visual stimuli in either hemifield (left vs. right of a fixation point) or along the vertical meridian (above or below fixation). The lateralized presentation of stimuli permits the study of hemispheric specialization for selective attentional processes. Attentional load is manipulated by presenting larger-sized target stimuli alone (i.e., the letter 'O') or smaller-sized target stimuli surrounded by flanking letters. This protocol report includes a description of subject exclusion criteria, procedural details, relevant experimental conditions and variables, suggestions for data analysis, expected results, and a discussion of the protocol's significance for attentional research along with suggestions for future research.

Attention↗
PubMed2000

Caspase 8 is deleted or silenced preferentially in childhood neuroblastomas with amplification of MYCN.

Caspase 8 is a cysteine protease regulated in both a death-receptor-dependent and -independent manner during apoptosis. Here, we report that the gene for caspase 8 is frequently inactivated in neuroblastoma, a childhood tumor of the peripheral nervous system. The gene is silenced through DNA methylation as well as through gene deletion. Complete inactivation of CASP8 occurred almost exclusively in neuroblastomas with amplification of the oncogene MYCN. Caspase 8-null neuroblastoma cells were resistant to death receptor- and doxorubicin-mediated apoptosis, deficits that were corrected by programmed expression of the enzyme. Thus, caspase 8 acts as a tumor suppressor in neuroblastomas with amplification of MYCN.

Antineoplastic Agents↗