Biomedical subjects

T Liu

Publications and source records attributed to T Liu.

At least 127 records · Page 7Linked to original sources

PubMed2001

[Study of cardiovascular and cerebrovascular disease in Chinese traditional medicines on Pb, Cr, Cd by AAS].

Cardiovascular and cerebrovascular disease are the common and frequently-occurring disease for the old man and are the main cause of death in the world. The Z-8000 polarized zeeman atomic absorption spectrophotometer was used for the determination of Pb, Cr, Cd in seventeen kinds of Chinese traditional medicines. And studied on Pb, Cr, Cd in Zhennao Ning, Di Ao Xinxue Kang, Linao Xin, Xueshuan Xinmai Ning et al. thirteen kinds of Chinese traditional medicines. The result shows that Chinese traditional medicines of cardiovascular and cerebrovascular drugs contain Pb, Cr, Cd and their efficacies are related to Pb, Cr, Cd.

Cadmium↗

PubMed2000

Total synthesis of (+/-)-deoxypenostatin A. Approaches to the syntheses of penostatins A and B.

A short synthesis of (+/-)-deoxypenostatin A (28) has been carried out using the convergent coupling of dienal 11, epoxide 13, and methylenetriphenylphosphorane (17) to prepare trienol 19 in only two steps. The key step is the Yb(OTf)(3)-catalyzed intramolecular Diels-Alder reaction of hydrated trienyl glyoxylate 23, which gives lactone 24 stereoselectively. Elaboration of lactone 24 to enone 27 by an intramolecular Horner-Emmons Wittig reaction and epimerization completes the synthesis of 28. Modest yields of Diels-Alder adducts 45a and 46a could be prepared analogously from MEM ether 44c, but the sensitivity of several of the intermediates precluded the elaboration of 45a to penostatin A (1).

Antineoplastic Agents↗

PubMed2000

Biochemical engineering of surface alpha 2-8 polysialic acid for immunotargeting tumor cells.

To target tumor cells for immunotherapy, we evaluated the feasibility of altering the epitopes on the surface polysialic acid of tumor cells. A precursor (N-propionylmannosamine), when incubated with leukemic cells, RBL-2H3 and RMA, resulted in substitution of the N-acetyl groups of surface alpha2-8 polysialic acid with N-propionyl groups. Expression of the altered alpha2-8 N-propionylpolysialic acid on the surface of tumor cells induced their susceptibility to cell death mediated by monoclonal antibody 13D9 (mAb 13D9), which specifically recognizes alpha2-8 N-propionylated polysialic acid. The expression of alpha2-8 N-propionylated polysialic acid and the lysis of tumor cells by antibody-dependent cytotoxicity depended on the time and dose of incorporation of N-propionylated mannosamine. In vivo, mAb 13D9 effectively controlled metastasis of leukemic cells RMA when mice were administered the precursor N-propionylated mannosamine.

Animals↗

PubMed2000

Decrease of neuronal nitric oxide synthase in the cerebellum of aged rats.

Nitric oxide (NO) is produced as an important neurotransmitter in the central nervous system (CNS) to participate in some pathophysiological pathways. In the present study, change of neuronal nitric oxide synthase (nNOS) was examined in isolated cerebellum of Wistar rats aged from 2 to 24 months. Northern blot showed a lower mRNA level of nNOS in rats aged 6, 12 and 24 months than that in rats aged 2 months. Western blot analysis also indicated that the expression of nNOS protein was lower in rats aged 6, 12 and 24 months than that of 2 months rats. However, the activity of nNOS determined by conversion of [(3)H] L-arginine to [(3)H] L-citrulline was decreased significantly in rats aged 24 months only. These results indicate the decrease of NOS expression in cerebellum of aged rat that seems helpful to explain the causes of malfunction in CNS of aged mammalian.

Aging↗

PubMed2000

Prion disease: A loss of antioxidant function?

Prion disease, a neurodegenerative disorder, is widely believed to arise when a cellular prion protein (PrP(C)) undergoes conformational changes to a pathogenic isoform (PrP(Sc)). Recent data have shown PrP(C) to be copper binding and that it acquires antioxidant activity as a result. This enzymatic property is dependent mainly on copper binding to the octarepeats region. In normal human brain and human prion disease, there is a population of brain-derived PrP that has been truncated at the N-terminal which encompassed the octarepeats region. Increasing evidences have suggested imbalances of metal-catalyzed reactions to be the common denominator for several neurodegenerative diseases. Therefore, we propose that one of the causative factors for prion disease could be due to the imbalances in metal-catalyzed reactions resulting in an alteration of the antioxidant function. These result in an increase level of oxidative stress and, as such, trigger the neurodegenerative cascade.

Antioxidants↗

PubMed2000

Identification of an epitope in the C terminus of normal prion protein whose expression is modulated by binding events in the N terminus.

We have characterized the epitopes of a panel of 12 monoclonal antibodies (Mabs) directed to normal human cellular prion protein (PrP(C)) using ELISA and Western blotting of recombinant PrP or synthetic peptide fragments of PrP. The first group of antibodies, which is represented by Mabs 5B2 and 8B4, reacts with PrP(23-145), indicating that the epitopes for these Mabs are located in the 23 to 145 N-terminal region of human PrP. The second group includes Mabs 1A1, 6H3, 7A9, 8C6, 8H4, 9H7 and 2G8. These antibodies bind to epitopes localized within N-terminally truncated recombinant PrP(90-231). Finally, Mabs 5C3, 2C9 and 7A12 recognize both PrP(23-145) and PrP(90-231), suggesting that the epitopes for this group are located in the region encompassing residues 90 to 145. By Western blotting with PepSpot(TM), only three of Mabs studied (5B2, 8B4 and 2G8) bind to linear epitopes that are present in 13-residue long synthetic peptides corresponding to human PrP fragments. The remaining nine Mabs appear to recognize conformational epitopes. Two N terminus-specific Mabs were found to prevent the binding of the C terminus-specific Mab 6H3. This observation suggests that the unstructured N-terminal region may influence the local conformation within the folded C-terminal domain of prion protein.

Amino Acid Sequence↗

PubMed2000

Identification of patients at risk by graded exercise testing in an emergency department chest pain center.

The study applied a retrospective follow-up design to determine the prognostic effect of graded exercise testing (GXT) in patients with low- to moderate-risk chest pain evaluated in an emergency department 9-hour protocol chest pain center (CPC) from January 1, 1993 to August 1, 1996. The cohort of 1,209 patients were followed to the date of death or first adverse cardiac event up to 1 year after CPC admission. Cardiac events were defined as coronary artery bypass graft, percutaneous transluminal coronary angioplasty, cardiogenic shock, cardiac-related death, congestive heart failure admission, ventricular tachycardia/ventricular fibrillation arrest, and myocardial infarction. Patients with acute ST-segment elevation or depression of >1 mm, positive enzyme (creatine kinase myocardial band) testing, or unstable angina during their CPC evaluation were admitted without GXT testing. Statistical analysis included chi-square test for complication rates and Cox proportional-hazards modeling. Nine hundred fifty-eight of 1,209 patients underwent GXT testing. Patients with positive, inconclusive, and normal GXTs had complication rates of 36.8% (7 of 19), 3.4% (9 of 267), and 1.1% (5 of 456), respectively. After adjusting for age, sex, and race, the relative risk of complication was 38.9 (95% confidence interval 11.7 to 129.6) with a positive GXT, and 3.6 (95% confidence interval 1.2 to 10.7) with an inconclusive GXT compared with a normal GXT. The GXT is a good prognostic indicator of adverse cardiac events in low- to moderate-risk chest pain in patients evaluated in an emergency department CPC.

Adolescent↗

PubMed2000

Binding of high density lipoprotein (HDL) and discoidal reconstituted HDL to the HDL receptor scavenger receptor class B type I. Effect of lipid association and APOA-I mutations on receptor binding.

The binding of apoA-I-containing ligands to the HDL receptor scavenger receptor class B type I (SR-BI) was characterized using two different assays. The first employed conventional binding or competition assays with (125)I-labeled ligands. The second is a new nonradioactive ligand binding assay, in which the receptor-associated ligand is detected by quantitative immunoblotting ("immunoreceptor assay"). Using both methods, we observed that the K(d) value for spherical HDL (density = 1.1-1.13 g/ml) was approximately 16 microgram of protein/ml, while the values for discoidal reconstituted HDL (rHDL) containing proapoA-I or plasma apoA-I were substantially lower (approximately 0.4-5 microgram of protein/ml). We also observed reduced affinity and/or competition for spherical (125)I-HDL cell association by higher relative to lower density HDL and very poor competition by lipid-free apoA-I and pre-beta-1 HDL. Deletion of either 58 carboxyl-terminal or 59 amino-terminal residues from apoA-I, relative to full-length control apoA-I, resulted in little or no change in the affinity of corresponding rHDL particles. However, rHDL particles containing a double mutant lacking both terminal domains competed poorly with spherical (125)I-HDL for binding to SR-BI. These findings suggest an important role for apoA-I and its conformation/organization within particles in mediating HDL binding to SR-BI and indicate that the NH(2) and COOH termini of apoA-I directly or indirectly contribute independently to binding to SR-BI.

Animals↗

PubMed2000

Differential contribution of superoxide dismutase activity by prion protein in vivo.

Normal prion protein (PrP(C)) is a copper binding protein and may play a role in cellular resistance to oxidative stress. Recently, copper-bound recombinant PrP(C) has been shown to exhibit superoxide dismutase (SOD)-like activity. However, as PrP(C) affinity for copper is low in comparison to other cupro-proteins, the question remains as to whether PrP(C) could contribute SOD activity in vivo. To unravel this enigma, we compared the SOD activity in lysates extracted from different regions of the brain from wild-type mice before and after the depletion of PrP(C). We found that removal of PrP(C) from the brain lysates reduced the levels of total SOD activity. The level of contribution to the total SOD activity was correlated to the level of PrP expressed and to the predominant form of PrP present in the specific brain region. Collectively, these results provide strong evidence that PrP(C) differentially contributes to the total SOD activity in vivo.

Animals↗

PubMed2000

ATP P2X receptors play little role in the maintenance of neuropathic hyperalgesia.

There is good evidence that ATP receptors play a role in nociception in the periphery. We sought evidence that they contribute to neuropathic hyperalgesia. We carried out a partial ligation of the sciatic nerve in rats to induce nerve injury and neuropathic hyperalgesia. Intrathecal injection of suramin (a P2 purinoceptor antagonist) provided minor alleviation of thermal hyperalgesia, while PPADS (a selective P2X receptor antagonist) had no effect. Both suramin and PPADS caused abnormal behavior including aggressiveness and subsequent hyporeactivity and immobility. P2X receptors in the spinal cord do not appear to play a significant role in the maintenance of thermal hyperalgesia. However, P2X receptors may play an important role in the control of behaviour.

Aggression↗

PubMed2000

Differences in interleukin-12 and -15 production by dendritic cells at the early stage of Listeria monocytogenes infection between BALB/c and C57 BL/6 mice.

The mechanisms responsible for the resistance of C57BL/6 mice and for the susceptibility of BALB/c mice to infection with Listeria monocytogenes were studied by comparing early IL-12 and IL-15 production by dendritic cells (DC) after infection with L. monocytogenes. Splenic DC expressing CD11b(low) and CD11c(+) obtained from C57BL/6 mice at 3 and 6 h after L. monocytogenes infection expressed higher levels of IL-12 p40 mRNA and IL-12 p40 protein than did those from BALB/c mice. Concurrently, a larger amount of IFN-gamma was produced by the splenic T cells from C57BL/6 mice in response to immobilized anti-TCRalphabeta mAb than by those from BALB/c mice, while the splenic T cells from BALB/c mice produced a higher level of IL-4 upon TCR alphabeta stimulation than did those of C57BL/6 mice. IL-15 mRNA and intracellular IL-15 protein were detected more abundantly in the DC from C57BL/6 mice than in those from BALB/c mice on day 3 after infection. CD3(+) IL2Rbeta (+) cells in the spleen were increased in C57BL/6 mice but not in BALB/c mice at the early stage after infection. Furthermore, IL-12Rbeta2 gene expression was up-regulated in T cells from C57BL/6 mice but not in those from BALB/c mice at the early stage after listerial infection. These results suggest that the difference in early production of IL-12 and IL-15 by DC may at least partly underlie the difference in susceptibility to L. monocytogenes between C57BL/6 and BALB/c mice.

Animals↗

PubMed2000

CD8(+) T cells can block herpes simplex virus type 1 (HSV-1) reactivation from latency in sensory neurons.

Recurrent herpes simplex virus type 1 (HSV-1) disease usually results from reactivation of latent virus in sensory neurons and transmission to peripheral sites. Therefore, defining the mechanisms that maintain HSV-1 in a latent state in sensory neurons may provide new approaches to reducing susceptibility to recurrent herpetic disease. After primary HSV-1 corneal infection, CD8(+) T cells infiltrate the trigeminal ganglia (TGs) of mice, and are retained in latently infected ganglia. Here we demonstrate that CD8(+) T cells that are present in the TGs at the time of excision can maintain HSV-1 in a latent state in sensory neurons in ex vivo TG cultures. Latently infected neurons expressed viral genome and some expressed HSV-1 immediate early and early proteins, but did not produce HSV-1 late proteins or infectious virions. Addition of anti-CD8alpha monoclonal antibody 5 d after culture initiation induced HSV-1 reactivation, as demonstrated by production of viral late proteins and infectious virions. Thus, CD8(+) T cells can prevent HSV-1 reactivation without destroying the infected neurons. We propose that when the intrinsic capacity of neurons to inhibit HSV-1 reactivation from latency is compromised, production of HSV-1 immediate early and early proteins might activate CD8(+) T cells aborting virion production.

Animals↗

PubMed2000

Cocaine-associated chest pain in a chest pain center.

Chest pain is the most common cocaine-related complaint. The objective of this study was to describe an emergency department-based chest pain center for patients with cocaine-associated chest pain and to evaluate the safety of this protocol by assessing cardiac complications at 30 days.

Adult↗

PubMed2000

Microsatellite instability as a predictor of a mutation in a DNA mismatch repair gene in familial colorectal cancer.

Germline alterations in human DNA mismatch repair genes are associated with hereditary nonpolyposis colorectal cancer (HNPCC). Mutation analysis of the genes reveals carriers with a high risk of colorectal cancer, who will benefit from surveillance. We wanted to find the best predictive parameter of a germline mutation in those genes among patients with familial colorectal cancer. Affected members from a total of 83 unrelated colorectal cancer families previously analyzed for mutations in MSH2 and MLH1 were used to evaluate different parameters' ability to predict a germline mutation. We studied various clinical criteria such as family structure, age of onset, and prevalence of endometrial cancer, as well as microsatellite instability in the tumors from the families. In total, 124 tumors from 59 of the families were tested for microsatellite instability (MSI) using PCR-based mono- and dinucleotide markers to establish whether the families could be scored as MSI-positive or -negative. The finding of MSI-positive tumors in a family was the best predictor of a germline mutation, and was found in 73% of the MSI-positive, but in less than 3% of the MSI-negative families (P < 0.0001). In contrast, MSI in unselected colorectal cancer is not as useful, since most of these MSI-positive tumors are sporadic. The finding of microsatellite instability in colorectal tumors seems efficient enough even to select those with germline mutations among families fulfilling HNPCC Amsterdam criteria, once used in identification of the DNA mismatch repair genes. Genes Chromosomes Cancer 27:17-25, 2000.

Adult↗

PubMed2000

Evolution of cis-acting elements in 5' flanking regions of vertebrate actin genes.

Regulation of the vertebrate actin multigene family involves the recognition of various regulatory sequences (cis-acting elements) that specify the distinct tissue type and developmental program of expression for each actin paralogue, which implies that the distribution of cis-acting elements may be unique for each paralogue gene. To elucidate the evolution of these unique distribution patterns, we improved a method to scan for cis-acting elements in the 5' flanking regulatory region of genes and used it to analyze five cis-acting elements (SRE, MyoD binding site, Elk-1 binding site, positive and negative YY1 binding sites) of six actin paralogue genes (beta and gamma cytoplasmic actins, alpha and gamma smooth muscle actins, and alpha skeletal and alpha cardiac actins) among various vertebrates. It was shown that although an element(s) may exist in all paralogue genes of the same species, its numbers, compositions, and distribution patterns or even sequences vary remarkably among paralogues, which contributes to their different tissue- and developmental-specific expression. However, each pair of coexpressed paralogues has some certain similarity in distribution patterns. Furthermore, among various orthologues of actin genes derived from diverse vertebrates, the sequences, numbers, and distribution patterns of these cis-acting elements are highly conserved or even identical in the long run of phylogeny of vertebrates. Taken together, the results described above strongly indicate that not only the structures of actins but also their expression patterns are essential in both the phylogeny and the physiology of vertebrates. The distribution patterns of cis-acting elements of various actin genes can be regarded as indicators of both horizontal (paralogues) and vertical (orthologous) evolution of actins.

Actins↗

PubMed2000

Depletion of macrophages reduces axonal degeneration and hyperalgesia following nerve injury.

Inflammatory mechanisms are believed to play an important role in hyperalgesia resulting from nerve injury. Hyperalgesia following nerve injury is temporally linked with Wallerian degeneration and macrophage recruitment, and is reduced in WLD mice, in which Wallerian degeneration is delayed. We sought more direct evidence that macrophages contribute to hyperalgesia and Wallerian degeneration by depleting macrophages with liposomes loaded with dichloromethylene diphosphonate (clodronate, Cl(2)MDP). Rats were subjected to partial ligation of the sciatic nerve. Intravenous injection of liposome-encapsulated clodronate reduced the number of macrophages in the injured nerve, alleviated thermal hyperalgesia and protected both myelinated and unmyelinated fibres against degeneration. The results confirm the role of circulating monocytes/macrophages in the development of neuropathic hyperalgesia and Wallerian degeneration due to partial nerve injury. Macrophage depletion immediately after nerve injury could have some clinical potential in prevention of neuropathic pain.

Analgesics, Non-Narcotic↗

PubMed2000

Hyperalgesia due to nerve injury-role of peroxynitrite.

We carried out a partial ligation of the sciatic nerve in rats to induce nerve injury and neuropathic hyperalgesia. We showed that nitrotyrosine, a marker of peroxynitrite activity, was formed after partial nerve injury. Double-labelling immunohistochemistry showed that nitrotyrosine-immunoreactive cells were mainly macrophages and Schwann cells. Daily treatment with uric acid, a scavenger of peroxynitrite, decreased nitrotyrosine formation in the injured sciatic nerve, and produced concomitant alleviation of thermal hyperalgesia and Wallerian degeneration. These results provide the first evidence that peroxynitrite is formed after partial nerve injury, and contributes to the initiation of thermal hyperalgesia and Wallerian degeneration. We hypothesize that uric acid alleviates hyperalgesia and Wallerian degeneration by inhibiting oxidative damage caused by peroxynitrite and possibly also by decreasing the production of other inflammatory mediators such as prostaglandins.

Animals↗

PubMed2000

Interacting interfaces of the P4 antirepressor E and the P2 immunity repressor C.

Antirepressors have been identified as proteins interacting with transcriptional repressors leading to expression of the repressed genes. The defective satellite phage/plasmid P4 has the capacity to derepress the unrelated prophage P2 after infection, thereby getting access to the late functions of the helper that are required for P4 lytic growth. The derepression of prophage P2 is mediated by the P4 E protein that function as an antirepressor by binding to the P2 immunity repressor C. A P2 mutant, sos, has been isolated that is insensitive to the action of the P4 E protein. In the present study, we show that sos is a point mutation in the P2 immunity repressor gene C and that it makes P4 E unable to turn the transcriptional switch of P2 from the lysogenic state to the lytic mode in a two plasmid reporter system. Furthermore, the interaction between C and E, when analysed in the yeast two-hybrid system, is blocked by the sos mutation. An analysis of C mutants indicates that the dimerization function of C is located in the C-terminal part of the protein and the dimerization defective mutants are unable to bind to their operator DNA. The sos mutation does not affect the capacity of the protein to dimerize. Using the yeast two-hybrid system, compensatory E mutants have been isolated that can interact with Sos, but they are unable to turn the transcriptional switch controlled by the Sos repressor. However, one point mutation in the E protein is shown to be unable to turn the transcriptional switch controlled by the wild-type C repressor.

Genes, Viral↗