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Biomedical subjects

M Ding

Publications and source records attributed to M Ding.

At least 37 records · Page 2Linked to original sources
PubMed2001

UV Induces phosphorylation of protein kinase B (Akt) at Ser-473 and Thr-308 in mouse epidermal Cl 41 cells through hydrogen peroxide.

The exposure of mammalian cells to UV irradiation leads to the activation of transcription factors and protein kinases, which are believed to be responsible for the carcinogenic effects of excessive sun exposure. The present study investigated the effect of UV exposure on reactive oxygen species (ROS) generation and protein kinase B (Akt) phosphorylation in epidermal cells and determined if a relationship exists between these UV responses. Exposure of mouse epidermal JB6 Cl 41 cells to UV radiation led to specific phosphorylation of Akt at Ser-473 and Thr-308 in a time-dependent manner. This phosphorylation was confirmed by the observation that overexpression of Akt mutant, Akt-T308/S473A, attenuated phosphorylation of Akt at Ser-473 and Thr-308. UV radiation also generated ROS as measured by electron spin resonance (ESR) in JB6 Cl 41 cells. The generation of ROS by UV radiation was measured further by H(2)O(2) and O(-.2) fluorescence staining assays. The mechanism of ROS generation involved reduction of molecular oxygen to O(-.2), which generated H(2)O(2) through dismutation. H(2)O(2) produced .OH via a metal-independent pathway. The scavenging of UV-generated H(2)O(2) by N-acety-l-cyteine (NAC, a general antioxidant) or catalase (a specific H(2)O(2) inhibitor) inhibited Akt phosphorylation at Ser-473 and Thr-308, whereas the pretreatment of cells with sodium formate (an .OH radical scavenger) or superoxide dismutase (an O(-.2) radical scavenger) did not show any inhibitory effects. Furthermore, treatment of cells with H(2)O(2) increased UV-induced phosphorylation of Akt at Ser-473 and Thr-308. These results demonstrate that UV radiation generates a whole spectrum of ROS including O(-.2), .OH, and H(2)O(2) and induces phosphorylation of Akt at Ser-473. Among the various ROS, H(2)O(2) seems most potent in mediating UV-induced phosphorylation of Akt at Ser-473 and Thr-308. It is possible that Akt may play a role in the carcinogenesis effects by UV radiation.

Animals↗
PubMed2001

Vanadium-induced nuclear factor of activated T cells activation through hydrogen peroxide.

The present study investigated the role of reactive oxygen species (ROS) in activation of nuclear factor of activated T cells (NFAT), a pivotal transcription factor responsible for regulation of cytokines, by vanadium in mouse embryo fibroblast PW cells or mouse epidermal Cl 41 cells. Exposure of cells to vanadium led to the transactivation of NFAT in a time- and dose-dependent manner. Scavenging of vanadium-induced H(2)O(2) with N-acety-L-cyteine (a general antioxidant) or catalase (a specific H(2)O(2) inhibitor) or the chelation of vanadate with deferoxamine, resulted in inhibition of NFAT activation. In contrast, an increase in H(2)O(2) generation by the addition of superoxide dismutase or NADPH enhanced vanadium-induced NFAT activation. This vanadate-mediated H(2)O(2) generation was verified by both electron spin resonance and fluorescence staining assay. These results demonstrate that H(2)O(2) plays an important role in vanadium-induced NFAT transactivation in two different cell types. Furthermore, pretreatment of cells with nifedipine, a calcium channel blocker, inhibited vanadium-induced NFAT activation, whereas and ionomycin, two calcium ionophores, had synergistic effects with vanadium for NFAT induction. Incubation of cells with cyclosporin A (CsA), a pharmacological inhibitor of the phosphatase calcineurin, blocked vanadium-induced NFAT activation. All data show that vanadium induces NFAT activation not only through a calcium-dependent and CsA-sensitive pathway but also involved H(2)O(2) generation, suggesting that H(2)O(2) may be involved in activation of calcium-calcineurin pathways for NFAT activation caused by vanadium exposure.

Animals↗
PubMed2001

Measurement of the recoil polarization in the p(e-->, e'p-->)pi(0) reaction at the Delta(1232) resonance.

The recoil proton polarization has been measured in the p(e-->,e'p-->)pi(0) reaction in parallel kinematics around W = 1232 MeV, Q2 = 0.121 (GeV/c)2, and epsilon = 0.718 using the polarized cw electron beam of the Mainz Microtron. All three proton polarization components, Px/P(e) = (-11.4+/-1.3+/-1.4)%, P(y) = (-43.1+/-1.3+/-2.2)%, and P(z)/P(e) = (56.2+/-1.5+/-2.6)%, could be measured simultaneously. The Coulomb quadrupole to magnetic dipole ratio, CMR = (-6.4+/-0.7(stat)+/-0.8(syst))%, was determined from Px in the framework of the Mainz Unitary Isobar Model. The consistency among the reduced polarizations and the extraction of the ratio of longitudinal-to-transverse response is discussed.

Journal Article↗
PubMed2001

[Frequent loss of heterozygosity on chromosome 4 in human hepatocellular carcinoma].

OBJECTIVE: Few previous studies have shown high frequency of loss of heterozygosity (LOH) on chromosome 4q in hepatocellular carcinoma (HCC). We define more clearly the deletion regions that may harbor the putative tumor suppressor genes in HCC. METHODS: Forty-eight cases of HCC and their corresponding non-tumor liver tissues were investigated with 12 microsatellite polymorphic markers for LOH. RESULTS: Twenty-one of 48 (44%) and 30 of 48 (63%) tumors showed LOH on at least one locus on the short and the long arms respectively. Two distinct common deleted regions (CDR) with different patterns of deletion were identified. The first CDR was located on 4q22-q25, between loci D4S392 and D4S1625. In addition, 17 of 27 (63%) of the informative tumors showed LOH on this region with locus D4S406 and constituted the highest rate of LOH on chromosome 4. The second CDR was located at 4q27-q31, between loci D4S1625 and D4S1652. CONCLUSION: There are at least two tumor suppressor loci on 4q.

Carcinoma, Hepatocellular↗
PubMed2001

Opposite effect of NF-kappa B and c-Jun N-terminal kinase on p53-independent GADD45 induction by arsenite.

Cell cycle checkpoint, a major genomic surveillance mechanism, is an important step in maintaining genomic stability and integrity in response to environmental stresses. Using cells derived from human bronchial epithelial cells, we demonstrate that NF-kappaB and c-Jun N-terminal kinase (JNK) reciprocally regulate arsenic trioxide (arsenite)-induced, p53-independent expression of GADD45 protein, a cell cycle checkpoint protein that arrests cells at the G(2)/M phase transition. Inhibition of NF-kappaB activation by stable expression of a kinase-mutated form of IkappaB kinase caused increased and prolonged induction of GADD45 by arsenite. In contrast, the induction of GADD45 by arsenite was transient and less potent in cells where the NF-kappaB activation pathway was normal. Analysis of the cell cycle profile by flow cytometry indicated that NF-kappaB inhibition potentiates arsenite-induced G(2)/M cell cycle arrest. Abrogation of JNK activation, on the other hand, decreased GADD45 expression induced by arsenite, suggesting a role for JNK activation in GADD45 induction. These results indicate a molecular mechanism by which NF-kappaB and JNK may differentially contribute to cell cycle regulation in response to arsenite.

Arsenites↗
PubMed2001

Urothelial function reconsidered: a role in urinary protein secretion.

Mammalian bladder epithelium functions as an effective permeability barrier. We demonstrate here that this epithelium can also function as a secretory tissue directly involved in modifying urinary protein composition. Our data indicate that normal bovine urothelium synthesizes, as its major differentiation products, two well-known proteases: tissue-type plasminogen activator and urokinase, as well as a serine protease inhibitor, PP5. Moreover, we demonstrate that the urothelium secretes these proteins in a polarized fashion into the urine via a cAMP- and calcium-regulated pathway. Urinary plasminogen activators of ruminants are therefore urothelium derived rather then kidney derived as in some other species; this heterogeneity may have evolved in response to different physiological or dietary factors. In conjunction with our recent finding that transgenic mouse urothelium can secrete ectopically expressed human growth hormone into the urine, our data establish that normal mammalian urothelium can function not only as a permeability barrier but also as a secretor of urinary proteins that can play physiological or pathological roles in the urinary tract.

3T3 Cells↗
PubMed2001

Event-related changes in neuromagnetic activity associated with syncopation and synchronization timing tasks.

For low rhythmic rates (1.0 to approximately 2.0 Hz), subjects are able to successfully coordinate finger flexion with an external metronome in either a syncopated (between the beats) or synchronized (on each beat) fashion. Beyond this rate, however, syncopation becomes unstable and subjects spontaneously switch to synchronization to maintain a 1:1 stimulus/response relationship. We used a whole-head magnetometer to investigate the spatiotemporal dynamics of neuromagnetic activity (MEG) associated with both coordinative patterns at eight different rates spanning the range 1.0-2.75 Hz. Timing changes in the event-related fields accompanied transitions from syncopation to synchronization and followed the placement of the motor response within each stimulus/response cycle. Decomposition of event-related fields into component auditory and motor brain responses revealed that the amplitude of the former decreased with increasing coordination rate whereas the motor contribution remained approximately constant across all rates. Such an interaction may contribute to changes in auditory-motor integration that cause syncopation to become unstable. Examination of event-related changes in high frequency bands revealed that MEG signal power in the beta band (15-30 Hz) was significantly lower during syncopated coordination in sensors covering the contralateral sensorimotor area suggesting a dependence of beta rhythm amplitude on task difficulty. Suppression of beta rhythms was also stronger during synchronization preceded by syncopation, e.g., after subjects had switched, when compared with a control condition in which subjects synchronized throughout the entire range of rates.

Acoustic Stimulation↗
PubMed2001

Evaluating causal relations in neural systems: granger causality, directed transfer function and statistical assessment of significance.

We consider the question of evaluating causal relations among neurobiological signals. In particular, we study the relation between the directed transfer function (DTF) and the well-accepted Granger causality, and show that DTF can be interpreted within the framework of Granger causality. In addition, we propose a method to assess the significance of causality measures. Finally, we demonstrate the applications of these measures to simulated data and actual neurobiological recordings.

Action Potentials↗
PubMed2001

Mechanical properties of cancellous bone in the human mandibular condyle are anisotropic.

The objective of the present study was (1) to test the hypothesis that the elastic and failure properties of the cancellous bone of the mandibular condyle depend on the loading direction, and (2) to relate these properties to bone density parameters. Uniaxial compression tests were performed on cylindrical specimens (n=47) obtained from the condyles of 24 embalmed cadavers. Two loading directions were examined, i.e., a direction coinciding with the predominant orientation of the plate-like trabeculae (axial loading) and a direction perpendicular to the plate-like trabeculae (transverse loading). Archimedes' principle was applied to determine bone density parameters. The cancellous bone was in axial loading 3.4 times stiffer and 2.8 times stronger upon failure than in transverse loading. High coefficients of correlation were found among the various mechanical properties and between them and the apparent density and volume fraction. The anisotropic mechanical properties can possibly be considered as a mechanical adaptation to the loading of the condyle in vivo.

Aged↗
PubMed2001

The coatomer of Trypanosoma brucei.

Coatomer is a multisubunit complex involved in trafficking of vesicles between the endoplasmatic reticulum and the Golgi apparatus. From sequence homologies, all seven subunits, alpha-, beta-, beta'-, gamma-, delta-, epsilon-, and zeta-COP, are encoded in the genome of Trypanosoma brucei. The complete predicted amino-acid sequences of beta-, beta'-, and zeta-COP show only 20-30% identity with higher eucaryotic homologues. The trypanosome coatomer complex was partially purified using a procedure similar to that used for bovine coatomer.

Amino Acid Sequence↗
PubMed2001

A decreased subchondral trabecular bone tissue elastic modulus is associated with pre-arthritic cartilage damage.

In osteoarthritis, one postulate is that changes in the mechanical properties of the subchondral bone layer result in cartilage damage. The goal of this study was to examine changes in subchondral trabecular bone properties at the calcified tissue level in the early stages of cartilage damage. Finite element models were constructed from microCT scans of trabectilar bone from the proximal tibia of donors with mild cartilage damage and from normal donors. In the donors with cartilage damage, macroscopic damage was present only in the medial compartment. The effective tissue elastic moduli were determined using a combination of finite element models and mechanical testing. The bone tissue modulus was reduced by 60% in the medial condyle of the cases with cartilage damage compared to the control specimens. Neither the presence of cartilage damage nor the anatomic site (medial vs. lateral) affected the elastic modulus at the apparent level. The volume fraction of trabecular bone was higher in the medial compartment compared to the lateral compartment of tibiae with cartilage damage (but not the controls), suggesting that mechanical properties were preserved in part at the apparent level by an increase in the bone volume fraction. It seems likely that the normal equilibrium between cartilage properties, bone tissue properties and bone volume fraction is disrupted early in the development of osteoarthritis.

Aged↗
PubMed2001

Bone density does not reflect mechanical properties in early-stage arthrosis.

Subchondral cancellous bone specimens were removed from 10 human postmortem early-stage arthrotic proximal tibiae (mean age 73 (63-81) years) and 10 age- and gender-matched normal proximal tibiae. The early-stage arthrosis was confirmed histologically and the specimens were divided into 4 groups: medial arthrosis, lateral control, normal medial and normal lateral controls. The specimens were tested in compression to determine mechanical properties and then physical/compositional properties. Compared to the normal medial control, we found reductions in ultimate stress, Young's modulus, and failure energy, and an increase in ultimate strain of arthrotic cancellous bone. Bone volume fraction, apparent density, apparent ash density, and collagen density were higher in cancellous bone with arthrosis, but no differences were found in tissue density, mineral and collagen concentrations between arthrotic cancellous bone and the 3 controls. None of the mechanical properties of arthrotic cancellous bone could be predicted by the physical/compositional properties measured. The increase in bone tissue in early-stage arthrotic cancellous bone did not make up for the loss of mechanical properties, which suggests a deterioration in the quality of arthrotic cancellous bone.

Aged↗
PubMed2001

Origins of timing errors in human sensorimotor coordination.

The authors analyzed fluctuations in timing errors when 8 human participants attempted to coordinate movement with external rhythmic signals. The temporal dynamics of the errors is usually described in terms of simple, self-correcting models. Here the authors demonstrate that timing errors are characterized by a 1/f(alpha) type of long memory process. The value of the exponent alpha differentiates different types of coordination states: synchronization and syncopation. More interesting, evidence was found that alpha can be changed when participants use different coordination strategies. Together with the authors' understanding of the generation mechanism for long memory processes, these results suggest that 1/f(alpha) type of long-range correlated timing errors are of higher cortical origin and are likely the outcome of distributed neural processes acting on multiple time scales.

Brain↗
PubMed2001

Human immunodeficiency virus type 1 env sequences from Calcutta in eastern India: identification of features that distinguish subtype C sequences in India from other subtype C sequences.

India is experiencing a rapid spread of human immunodeficiency virus type 1 (HIV-1), primarily through heterosexual transmission of subtype C viruses. To delineate the molecular features of HIV-1 circulating in India, we sequenced the V3-V4 region of viral env from 21 individuals attending an HIV clinic in Calcutta, the most populous city in the eastern part of the country, and analyzed these and the other Indian sequences in the HIV database. Twenty individuals were infected with viruses having a subtype C env, and one had viruses with a subtype A env. Analyses of 192 subtype C sequences that included one sequence for each subject from this study and from the HIV database revealed that almost all sequences from India, along with a small number from other countries, form a phylogenetically distinct lineage within subtype C, which we designate C(IN). Overall, C(IN) lineage sequences were more closely related to each other (level of diversity, 10.2%) than to subtype C sequences from Botswana, Burundi, South Africa, Tanzania, and Zimbabwe (range, 15.3 to 20.7%). Of the three positions identified as signature amino acid substitution sites for C(IN) sequences (K340E, K350A, and G429E), 56% of the C(IN) sequences contained all three amino acids while 87% of the sequences contained at least two of these substitutions. Among the non-C(IN) sequences, all three amino acids were present in 2%, while 22% contained two or more of these amino acids. These results suggest that much of the current Indian epidemic is descended from a single introduction into the country. Identification of conserved signature amino acid positions could assist epidemiologic tracking and has implications for the development of a vaccine against subtype C HIV-1 in India.

Adult↗
PubMed2001

Reactive oxygen species and molecular mechanism of silica-induced lung injury.

Silica particles are considered to be fibrogenic and carcinogenic agents, but the mechanisms of disease initiation and progression are not fully understood. This article summarizes the literature on the generation of reactive oxygen species (ROS) directly from interaction of silica with aqueous medium and from silica-stimulated cells. This article also discusses the role of ROS in silica-induced lung injury, with particular focus on the silica-induced NF-kappaB activation, including the molecular mechanisms of its regulation, its possible attenuation, and its relationship to silica-induced generation of cyclooxygenase II and TNF-alpha.

Air Pollutants, Occupational↗