PubMed Health⌕ Search

Biomedical subjects

J She

Publications and source records attributed to J She.

At least 19 recordsLinked to original sources
PubMed2002

Early chronic aluminium exposure impairs long-term potentiation and depression to the rat dentate gyrus in vivo.

As an important neurotoxin, aluminium can cause cognitive dysfunctions and mental diseases. Previous studies have reported that aluminium impaired long-term potentiation (LTP) in vivo and in vitro. Here, we utilise two models of synaptic plasticity, LTP and long-term depression (LTD) to study the effects of aluminium on synaptic plasticity in vivo. Neonatal Wistar rats were chronically exposed to aluminium from birth to weaning via the milk of dams fed with 0.3% aluminium chloride solution. Excitatory postsynaptic potential (EPSP) and population spikes (PS) were recorded from the dentate gyrus (DG) of adult rats by electrically stimulating the perforant path. THE FOLLOWING RESULTS WERE OBTAINED: (1) The input/output function indicated that, as compared to controls, aluminium increased the baseline amplitude of the PS, but decreased the baseline slope of EPSP. (2) Aluminium significantly prevented LTD in PS (controls: 77.36+/-6.7%, n=7; aluminium-exposed: 102.01+/-9.1%, n=7; P<0.05) and decreased the LTD amplitude in EPSP (controls: 76.61+/-4.1%, n=7; aluminium-exposed: 94.31+/-7.9% n=7, P<0.05). (3) Aluminium reduced the amplitude of LTP in both PS (controls: 190+/-16.1%, n=7; aluminium-exposed: 135+/-9.7%, n=7; P<0.05) and EPSP (control: 132+/-9.3%, n=7; aluminium-exposed: 115+/-10.6%, n=7; P<0.05). As for LTD and LTP, PS was impaired more seriously than EPSP in aluminium-exposed rats. (4) Aluminium exposure decreased the paired-pulse facilitation (PPF) of PS at 30-150 ms interpulse interval (IPI), and reduced 93.5% of PPF at 80 ms IPI in PS (controls: 243.4+/-39.8%, n=7; aluminium-exposed: 149.9+/-12.3%, n=7). There was no significant difference in EPSP of PPF. From these results we conclude that aluminium exposure in neonatal rats thus reduces the amplitude of LTP and PPF and blocks the induction of LTD in the DG. We suggest that aluminium affects both presynaptic and postsynaptic mechanisms of synaptic transmission.

Aluminum↗
PubMed1999

T lymphocyte development in the absence of CD3 epsilon or CD3 gamma delta epsilon zeta.

CD3 gamma, delta, epsilon, and zeta proteins together with the pre-TCR alpha-chain (pT alpha) and a rearranged TCR beta-chain assemble to form the pre-TCR that controls the double negative (DN) to double positive (DP) stages of thymopoiesis. The CD3 proteins are expressed before pT alpha and TCR beta-chains in prothymocytes and are expressed intracellularly in precursor NK cells, suggesting that the CD3 complex may function independent of pT alpha and TCR beta. In this report, both the role of CD3 epsilon exclusively, and the role of CD3 proteins collectively, in thymocyte and NK cell development were examined. In a mouse strain termed E delta P, a neomycin cassette inserted within the CD3 epsilon promoter abolishes CD3 epsilon and delta expression and also abolishes CD3 gamma expression in all but a small minority (< or =1%) of prothymocytes. These prothymocytes became deficient in CD3 epsilon alone upon reconstitution of CD3 delta expression and were severely, but not completely, arrested at the DN stage, as small numbers of double positive thymocytes were detected. In de facto CD3 gamma delta epsilon zeta(null) mice generated by crossing the epsilon delta P mice with CD3 zeta-/- mice, thymopoiesis were arrested at the CD44-CD25+ DN stage as observed in RAG-/- mice, DJ and VDJ recombination at the TCR beta locus was functional, and normal numbers of NK cells were detected. Together, the findings demonstrate that during thymocyte development, the CD3 complex collectively is not essential until the critical CD44-CD25+ DN stage in which pre-TCR begins to function, whereas CD3 epsilon is critical for the assembly of pre-TCR. Moreover, CD3 proteins are dispensable for NK cell development.

Animals↗
PubMed1999

Generation of antigen-specific cytotoxic T lymphocytes and regulation of cytokine production takes place in the absence of CD3zeta.

The TCR-associated protein CD3zeta plays a major role in regulating the state of responsiveness to peptide-MHC complexes on the surface of antigen-presenting cells. In this paper the requirement of CD3zeta in the generation of cytotoxic T cells was compared with its requirement in cytokine gene activation in two mutant mice: ZKO mice with a disrupted CD3zeta gene and ZTG mice in which a truncated CD3zeta segment was expressed as a transgene on the ZKO background. Upon infection of ZTG mice with lymphocytic choriomeningitis virus (LCMV), antigen-specific cytotoxic T lymphocyte (CTL) responses were detected, identical to responses in wild-type mice. In addition, antigen-specific CTL responses to allogeneic class I and class II MHC in ZTG animals were indistinguishable from those in wild-type animals. However, CTL responses to the same major antigens were not detectable in ZKO mice. We conclude that the signal transduction pathways leading to CTL development and cytokine production can be triggered through TCR in the absence of functional CD3zeta, provided the remainder of the TCR-CD3 complex is expressed at high levels on the cell surface. Surprisingly, IFN-gamma production in response to LCMV followed the same kinetics in ZKO, ZTG and wild-type mice. However, in vitro studies showed that cytokine production in general was abnormally regulated in T lymphocytes from ZKO mice, in contrast to ZTG T cells. Taken together, these studies support the hypothesis that development of CTL can take place in the absence of functional CD3zeta. However, CTL development requires stronger TCR-initiated signal transduction events than induction of cytokine genes.

Abatacept↗
PubMed1999

Inhibitory effects of sodium quercetin monosulfate on pig platelet aggregation induced by thrombin.

AIM: To study the inhibitory effects of sodium quercetin monosulfate (SQMS) on pig platelet aggregation induced by thrombin. METHODS: Platelet aggregation was analyzed by turbidimetry. Cytosolic free calcium concentration ([Ca2+]i) was determined by Fura-2 fluorescence. Activity of protein kinase C (PKC) was assayed by incubating PKC with histone III S and [gamma-32 P] ATP. The cytoskeletal proteins were precipitated by Triton X-100 and separated by SDS-PAGE. RESULTS: SQMS inhibited the platelet aggregation induced by thrombin 500 U.L-1 with IC50 132 (50-347) mumol.L-1. SQMS inhibited Ca2+ influx in blood platelets induced by thrombin 500 U.L-1 in the presence of extracellular Ca2+ 1 mmol.L-1 with IC50 20 (9-46) mumol.L-1; SQMS inhibited the internal Ca2+ release in the absence of extracellular Ca2+. SQMS also decreased [Ca2+]i level in quiescent blood platelets. SQMS (10-160 mumol.L-1) inhibited the activity of cytosolic PKC from blood platelets in a concentration-dependent manner, but had no effect on membrane PKC. SQMS (20-80 mumol.L-1) inhibited the actin polymerization induced by thrombin 500 U.L-1 inblood platelets in a concentration-dependent manner. CONCLUSION: SQMS inhibited pig platelet aggregation induced by thrombin and its mechanism might be due to its inhibitions of Ca2+ influx, internal Ca2- release, PKC activity, and actin polymerization.

Actins↗
PubMed1998

Essential and partially overlapping role of CD3gamma and CD3delta for development of alphabeta and gammadelta T lymphocytes.

CD3gamma and CD3delta are two highly related components of the T cell receptor (TCR)-CD3 complex which is essential for the assembly and signal transduction of the T cell receptor on mature T cells. In gene knockout mice deficient in either CD3delta or CD3gamma, early thymic development mediated by pre-TCR was either undisturbed or severely blocked, respectively, and small numbers of TCR-alphabeta+ T cells were detected in the periphery of both mice. gammadelta T cell development was either normal in CD3delta-/- mice or partially blocked in CD3gamma-/- mice. To examine the collective role of CD3gamma and CD3delta in the assembly and function of pre-TCR and in the development of gammadelta T cells, we generated a mouse strain with a disruption in both CD3gamma and CD3delta genes (CD3gammadelta-/-). In contrast to mice deficient in either CD3gamma or CD3delta chains, early thymic development mediated by pre-TCR is completely blocked, and TCR-alphabeta+ or TCR-gammadelta+ T cells were absent in the CD3gammadelta-/- mice. Taken together, these studies demonstrated that CD3gamma and CD3delta play an essential, yet partially overlapping, role in the development of both alphabeta and gammadelta T cell lineages.

Animals↗
PubMed1998

Congener-specific analysis of PCBs in human milk from Kazakhstan.

We have characterized the spectrum of PCB contaminants in human milk samples from 95 women in Kazakhstan using GC/MS congener specific analysis. In these samples, 12 PCBs comprised 83% of total PCB concentration, and were similar to the major PCBs reported in other published human milk studies. By summing concentration levels of 80 PCB congeners in the Kazakhstan samples, a mean total PCB concentration of 368 ng/g fat was obtained. This is lower than levels reported in human milk samples from Western Europe. Six indicator PCBs were summed in Kazakh milk samples; their aggregate value was similar to literature values published for human milk from the former Soviet Union. Using WHO's recent TEF scheme, the mean sum of PCDD/F, coplanar PCB, mono-ortho PCB, and di-ortho PCB TEQ is 42 pg TEQ/g fat.

Benzofurans↗
PubMed1998

Activation-induced apoptosis of mature T cells is dependent upon the level of surface TCR but not on the presence of the CD3 zeta ITAM.

Activation-induced cell death (AICD) occurs primarily in recently activated T cells after a second TCR triggering. Since a threshold in the activation status may be critical for AICD, it is likely that the CD3 ITAM, docking sites for tyrosine kinases, regulate AICD. A 'threshold model' for AICD was tested by using two targeted mutant mouse strains lacking either the zeta chain (CD3zeta-/-) or the ITAM of the zeta chain (CD3zeta-/-:Tgzetadelta67-150). Although the T cells from the CD3zeta-/- mice express extremely low levels of surface TCR, a subpopulation (approximately 18%) of activated T cells could be induced to express TCR/FcepsilonRI gamma by using a powerful polyclonal activation protocol. These activated TCR/FcRI gamma T cells were capable of undergoing AICD, but its induction required 10 times as much anti-CD3epsilon mAb as that required for AICD of wild-type T cells. Thus, the intensity of AICD correlated with the level of CD3 expression and was less efficient with activated, CD3zeta(-/-)-derived T cells. By contrast, AICD of T cells from the CD3zeta-/-:Tgzetadelta67-150 mice could be induced with low doses of anti-CD3epsilon mAb and the extent of AICD was comparable to T cells from wild-type mice. The AICD induced in T cells from CD3-/-, CD3zeta-/-:Tgzetadelta67-150 and normal controls was specifically inhibited by Fas-Ig fusion proteins. Our data support the 'threshold model' of AICD by demonstrating that AICD is controlled by the strength of T cell activation.

Animals↗
PubMed1998

Expression of a CD3 epsilon transgene in CD3 epsilon(null) mice does not restore CD3 gamma and delta expression but efficiently rescues T cell development from a subpopulation of prothymocytes.

The TCR-associated CD3 complex consists of four subunits, i.e. CD3 gamma, delta, epsilon and zeta, which are expressed very early in T cell development prior to the expression of the TCR and the pre-TCR alpha chain. It is unclear whether the expression of each CD3 protein is independent of, or is influenced by, other CD3 subunits. To study whether CD3 epsilon regulates expression of CD3 gamma and delta genes, we generated a strain of CD3 epsilon-deficient mice termed CD3 epsilon(delta P/delta P) (epsilon(delta P)), in which the promoter of CD3E was disrupted, and subsequently reconstituted these mice with a CD3 epsilon transgene. In the epsilon(delta P) mice, T cell development is arrested at the double-negative stage and targeting the CD3 epsilon gene caused severe inhibition of CD3 gamma and delta gene expression. Introduction of the CD3 epsilon transgene did not restore CD3 gamma and delta expression. However, a very small fraction of prothymocytes that expressed CD3 gamma and delta was rescued upon reconstitution of the CD3 epsilon transgene. Remarkably, this rescue led to a very efficient differentiation and maturation of thymocytes, resulting in a significant T cell population in the periphery. These results demonstrate that CD3 epsilon does not regulate expression of CD3 gamma and delta genes, and underscore the capacity of each prothymocyte to give rise to a large number of mature peripheral T cells.

Animals↗
PubMed1998

Analysis of breast milk to assess exposure to chlorinated contaminants in Kazakstan: high levels of 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD) in agricultural villages of southern Kazakstan.

To assess levels of chlorinated contaminants in breast milk, we measured organochlorine pesticides, polychlorinated biphenyls, polychlorinated dibenzo-p-dioxins (PCDDs), and polychlorinated dibenzofurans (PCDFs) in breast milk samples collected in 1994 according to the World Health Organization protocol from 92 donors that were representative of regional populations in southern Kazakstan. High levels (10-120 pg/g fat) of 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD), the most toxic of the PCDD/PCDF congeners, were found in breast milk samples from an agricultural region. TCDD was the major contributor (75%) to the international toxicity equivalents of these samples. The same distinctive PCDD/PCDF congener pattern was found in 15 breast milk samples and 4 serum samples collected in 1996 in a follow-up study, and has now been confirmed by three analytical laboratories.

Adolescent↗
PubMed1997

CD16-expressing CD8alpha alpha+ T lymphocytes in the intestinal epithelium: possible precursors of Fc gammaR-CD8alpha alpha+ T cells.

T lymphocytes normally express their Ag receptors in association with the CD3 proteins, which include CD3zeta. In CD3zeta eta(null) mice thymic and peripheral T lymphocytes do not express the TCR/CD3 complex on their surface due to retention in the endoplasmic reticulum of the remaining polypeptide chains. However, intestinal intraepithelial lymphocytes (iIEL) of CD3zeta eta(null) mice do express surface TCR, because the Fc epsilonRI gamma chain replaced the CD3zeta chain in the TCR/CD3 complex. Here we report that in a subset of CD8alpha alpha+ iIEL the presence of the Fc epsilonRI gamma chain could be accounted for by the surface expression of the Fc gammaRIII(CD16) complex. Because in wild-type (wt) mice only CD16+ iIEL coexpressed Fc epsilonRI gamma and CD3zeta, we concluded that the presence of Fc epsilonRI gamma was dictated by its required participation of CD16 complex. CD8alpha alpha+ iIEL bearing CD16 and B220 were also detected in the intestinal mucosa of RAG-2(null) mice from 12 days after birth onward. Two independent experimental settings were used in an attempt to demonstrate that CD16+ iIEL matured into CD16- T cells. First, in the RAG-2(null) mice, iIEL responded to in vivo administration of an anti-CD3epsilon mAb by progression to a more mature stage of development, characterized by a loss of CD16 and B220. Secondly, a conversion to CD16- iIEL occurred upon transfer of wt CD16+ iIEL into RAG-2(null) mice. We conclude from these experiments that in both RAG-2(null) and wt mice, a precursor/progeny relationship may exists between CD16+ B220+ CD8alpha alpha+ and CD16- B220- CD8alpha alpha+ iIEL.

Animals↗
PubMed1997

Analysis of breast milk to assess exposure to chlorinated contaminants in Kazakstan: PCBs and organochlorine pesticides in southern Kazakstan.

Organochlorine pesticides (OC) and polychlorinated biphenyls (PCBs) were measured in samples of breast milk taken from 92 donors representative of regional populations in southern Kazakstan. The World Health Organization protocol for assessing levels of chlorinated contaminants in breast milk was followed. The most prevalent OC residues were beta-hexachlorocyclohexane (beta-HCH), p,p'-DDE, p,p'-DDT, hexachlorobenzene, and alpha-HCH. The measured levels of beta-HCH were among the highest reported in the published literature. Data from Aralsk, near the Aral Sea, indicated continuing DDT exposure. Overall PCB-toxic equivalent levels (22 pg/g fat) were similar to those reported in industrialized European countries. PCBs were highest in Atyrau in the Caspian oilfields.

Adolescent↗
PubMed1997

CD3-epsilon overexpressed in prothymocytes acts as an oncogene.

BACKGROUND: Upon engagement of the T cell receptor for antigen, its associated CD3 proteins recruit signal transduction molecules, which in turn regulate T lymphocyte proliferation, apoptosis, and thymocyte development. Because some signal transducing molecules recruited by CD3-epsilon, i.e., p56lck and p59fyn, are oncogenic and since we previously found that overexpression of CD3-epsilon transgenes causes a block in T lymphocyte and NK cell development, we tested the hypothesis that aberrant CD3-epsilon signaling leads both to abnormal T lymphocyte death and lymphomagenesis. MATERIALS AND METHODS: Ten independently derived transgenic mouse lines were generated with four different genomic CD3-epsilon constructs. Mice either homozygous or hemizygous for each transgene were analyzed for an arrest in T lymphocyte development and for the occurrence of T cell lymphomas. RESULTS: Aggressive clonal T cell lymphomas developed at very high frequencies in seven mouse lines with intermediate levels of copies of CD3-epsilon derived transgenes. However, these lymphomas were not found when high copy numbers of CD3-epsilon transgenes caused a complete block in early thymic development or when a transgene was used in which the exons coding for the CD3-epsilon protein were deleted. Analyses of a series of double mutant mice, tgCD3-epsilon x RAG-2null, indicated that lymphomagenesis was initiated in lineage-committed prothymocytes, i.e., before rearrangement of the T cell receptor genes. In addition, the transgene coding for the CD3-epsilon cytoplasmic domain and its transmembrane region induced a T cell differentiation signal in premalignant tgCD3-epsilon x RAG-2null mice. CONCLUSION: The nonenzymatic CD3-epsilon protein acted as a potent oncogene when overexpressed early in T lymphocyte development. Lymphomagenesis was dependent on signal transduction events initiated by the cytoplasmic domain of CD3-epsilon.

Animals↗
PubMed1996

Numerical simulation of collapsible-tube flows with sinusoidal forced oscillations.

Collapsible-tube flow with self-excited oscillations has been extensively investigated. Though physiologically relevant, forced oscillation coupled with self-excited oscillation has received little attention in this context. Based on an ODE model of collapsible-tube flow, the present study applies modern dynamics methods to investigate numerically the responses of forced oscillation to a limit-cycle oscillation which has topological characteristics discovered in previous unforced experiments. A devil's staircase and period-doubling cascades are presented with forcing frequency and amplitude as control parameters. In both cases, details are provided in a bifurcation diagram. Poincaré sections, a frequency spectrum and the largest Lyapunov exponents verify the existence of chaos in some circumstances. The thin fractal structure found in the strange attractors is believed to be a result of high damping and low stiffness in such systems.

Animals↗
PubMed1996

[Induced-expression of MHC-DR molecules on mice islet cells].

The correlation of induced-expression of MHC-DR molecules with insulin release in cultured mice islet cells has been studied. The results showed that, (1) No detectable induced-expression of MHC-DR molecules by TNF-alpha alone at the concentration of 50-100 U/ml has been assayed, but the induced-expression of MHC-DR molecules has been identified in a few islet cells (8.5 +/- 2.9%) with IFN-r alone at concentration of 50-100 U/ml. (2) The induced-expression of MHC-DR molecules has been detected in as high as 80% of cultured islet cells with TNF-alpha and IFN-r combined at different concentrations. (3) Insulin released from cultured islet cells was enhanced by IFN-r and TNF-alpha either alone or combined at different concentrations. These results suggest that the induced-expression of MHC-DR molecules themselves does not damage the function for insulin release in cultured islet cells.

Animals↗
PubMed1995

Severe colitis in mice with aberrant thymic selection.

Tg epsilon 26 mice display an arrest very early in T cell development that has a profound effect on the architecture of thymic stromal cells. We have recently demonstrated that transplantation of wild-type bone marrow cells restores the thymic microenvironment of fetal but not adult Tg epsilon 26 mice. Here, we report that T cell-reconstituted adult Tg epsilon 26 mice develop a spontaneous wasting syndrome characterized by extensive inflammation of the colon, resembling human ulcerative colitis. Colitis in these animals was marked by substantial infiltration of the colon by activated thymus-derived CD4+ T cells. Importantly, bone marrow-transplanted Tg epsilon 26 mice previously engrafted with a fetal Tg epsilon 26 thymus did not develop colitis. These results suggest that T cells selected in an aberrant thymic microenvironment contain a population of cells able to induce severe colitis that can be prevented by T cells that have undergone normal thymic development.

Animals↗