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Biomedical subjects

H Hu

Publications and source records attributed to H Hu.

At least 55 records · Page 3Linked to original sources
PubMed2001

Biochemical characterization of the thioredoxin domain of Escherichia coli DsbE protein reveals a weak reductant.

Thioredoxin (Trx) domain is a typical fold functioning in thiol/disulfide exchange. DsbE protein is one of the Trx-domain containing proteins involved in electron transfer for cytochrome c maturation in the periplasm of Escherichia coli. The soluble C-terminal Trx domain of DsbE protein was overexpressed and purified to homogeneity. We herein report biochemical characterization of the structural and redox properties of this domain. During redox reaction, the domain undergoes a structural transformation resulting in a more stable reduced form with a free energy difference (DeltaDeltaG(Redox)) of ca. 5 kcal/mol, but the thiol/disulfide exchange exhibits very low reactivity. The standard redox potential (E0') for the active thiol/disulfide is -0.175 V and the pK(a) value of the active cysteine is around 6.8, indicating that the domain acts as a weak reductant. This implies that the membrane-anchored DsbE protein may provide driven reducing power for the redox reaction in the thiol/disulfide exchange pathway.

Circular Dichroism↗
PubMed2001

Plexin-B semaphorin receptors interact directly with active Rac and regulate the actin cytoskeleton by activating Rho.

Semaphorins and their receptors, plexins, are widely expressed in embryonic and adult tissues. In general, their functions are poorly characterized, but in neurons they provide essential attractive and repulsive cues that are necessary for axon guidance [1-3]. The Rho family GTPases Rho, Rac, and Cdc42 control signal transduction pathways that link plasma membrane receptors to the actin cytoskeleton and thus regulate many actin-driven processes, including cell migration and axon guidance [4-7]. Using yeast two-hybrid screening and in vitro interaction assays, we show that Rac in its active, GTP bound state interacts directly with the cytoplasmic domain of mammalian and Drosophila B plexins. Plexin-B1 clustering in fibroblasts does not cause the formation of lamellipodia, which suggests that Rac is not activated. Instead, it results in the assembly of actin:myosin filaments and cell contraction, which indicates Rho activation. Surprisingly, these cytoskeletal changes are both Rac and Rho dependent. Clustering of a mutant plexin, lacking the Rac binding region, induced similar cytoskeletal changes, and this finding indicates that the physical interaction of plexin-B1 with Rac is not required for Rho activation. Our findings that plexin-B signaling to the cytoskeleton is both Rac and Rho dependent form a starting point for unraveling the mechanism by which semaphorins and plexins control axon guidance and cell migration.

3T3 Cells↗
PubMed2001

Marginal Fermi liquid resonance induced by a quantum magnetic impurity in d-wave superconductors.

We consider a model of an Anderson impurity embedded in a d(x(2)-y(2))--wave superconducting state to describe the low-energy excitations of cuprate superconductors doped with a small amount of magnetic impurities. Because of the Dirac-like energy dispersion, a sharp localized resonance above the Fermi energy, showing a marginal Fermi liquid behavior ( omega ln omega as omega-->0), is predicted for the impurity states. The same logarithmic dependence of self-energy and a linear frequency dependence of the relaxation rate are also derived for the conduction electrons, characterizing a new universality class for the strong coupling fixed point. At the resonant energies, the spatial distribution of the electron density of states around the magnetic impurity is also calculated.

Journal Article↗
PubMed2001

Bone lead and blood lead levels in relation to baseline blood pressure and the prospective development of hypertension: the Normative Aging Study.

Between 1991 and 1997, the authors studied 833 participants of the Normative Aging Study in a substudy of bone lead levels (measured by K-shell x-ray fluorescence), blood lead levels, and hypertension. Among these subjects, 337 were classified as normotensive, and 182 and 314 were classified as having borderline and definite hypertension, respectively, at baseline. These bone and blood lead levels were typical of those of community-exposed men. Among the 519 subjects with no history of definite hypertension at baseline, cross-sectional analyses revealed positive associations between systolic blood pressure and bone lead levels. Of the 474 subjects who were free from definite hypertension at baseline and had follow-up data, 74 new cases of definite hypertension were reported. Baseline bone lead levels were positively associated with incidence of hypertension. In proportional hazards models that controlled for age, age squared, body mass index, and family history of hypertension, an increase in patella (trabecular) lead from the midpoint of the lowest quintile to that of the highest quintile was associated with a rate ratio of definite hypertension of 1.71 (95% confidence interval: 1.08, 2.70). No association was found with blood lead level. These results support the hypothesis that cumulative exposure to lead, even at low levels sustained by the general population, may increase the risk of hypertension.

Adult↗
PubMed2001

A regulatory role for cytoplasmic YVKM motif in CTLA-4 inhibition of TCR signaling.

CTLA-4 negatively regulates TCR signaling, although the molecular basis for this effect has yet to be elucidated. The cytoplasmic YVKM motif, while binding to phosphatidylinositol 3-kinase, SHP-2 and the AP-1/AP-2 clathrin adaptor complexes, has been reported to play no role in CTLA-4 function. In contrast, in this study, we demonstrate that, although not essential, the YVKM motif contributes to optimal CTLA-4 blockage of TCRzeta or combined TCRzeta/CD28 signaling. Significantly, dependency on the YVKM motif varied with the mode of anti-receptor presentation, where soluble antibody ligation was more dependent on the presence of the motif than immobilized antibody. Previous studies have mainly relied on the use of immobilized antibody. Neither SHP-2 binding, alterations in TCRzeta chain phosphorylation, nor ZAP-70 recruitment was involved in CTLA-4 wild-type or mutant inhibition. Overall, our findings clearly implicate the YVKM motif in optimal CTLA-4 function.

Abatacept↗
PubMed2001

P53-independent downregulation of p73 in human cancer cells treated with Adriamycin.

UNLABELLED: P73, a new p53 homologue, has been recently identified as a candidate tumor suppressor gene. PURPOSE: We studied the alterations in p73 in a panel of human cancer cell lines treated with the chemotherapeutic agent, Adriamycin (ADR), in comparison with the changes in p53. METHODS: P73 and p53 mRNA and protein were determined using semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, respectively. ADR cytotoxicity was examined by a trypan blue dye exclusion assay. RESULTS: The cell lines bearing wild-type p53 were more susceptible to ADR than the cell lines bearing mutant p53. ADR treatment resulted in a significant accumulation of p53 protein and mRNA expression in the wild-type p53 cell lines and caused little (slight increase) or no influence on p53 expression in the cell lines with p53 mutation and deletion. However, in striking contrast to the alterations in p53, a decline in p73 at both the protein and mRNA levels was observed in all the cell lines examined following ADR treatment. Further studies indicated that this p53-independent downregulation of p73 was induced by ADR in a dose- and time-dependent manner. Moreover, the p73 protein decline was abrogated by the presence of proteasome inhibitors. CONCLUSIONS: Our findings revealed that although p73 shares a similar structural and functional composition with p53, there is a significant difference in the mechanisms that govern the responses of p53 and p73 to ADR-induced DNA damage.

Antibiotics, Antineoplastic↗
PubMed2001

Analysis of chromosomal and organellar DNA of somatic hybrids between Triticum aestiuvm and Haynaldia villosa Schur.

Intergeneric somatic hybridization between wheat (cv. Jinan 177) protoplasts that have 24-28 chromosomes and Haynaldia villosa protoplasts containing 11-14 chromosomes was carried out by the polyethylene glycol (PEG) method. A high frequency of hybrid calli and plants were obtained from the fusion products, as revealed by cytological and biochemical techniques and by PCR analysis of 5S rDNA spacer sequences. GISH (genomic in situ hybridization) analysis confirmed the presence of chromosomes from both parents in the hybrid clones and the common occurrence of translocations between them. The RFLP analysis of the organellar DNA using mitochondrion- and chloroplast-specific probes revealed that mitochondria from both parents existed in the cells of hybrid calli and their recombination, whereas chloroplasts segregated and recombined randomly. The gross morphology of hybrid plants resembled that of wheat, but the gross morphology of their ovaries and anthers were intermediate between those of the two parents. The relationship between hybrid plant regeneration and the balance of genetic materials in hybrid clones is discussed.

Blotting, Southern↗
PubMed2001

Longitudinal observations on mutations conferring ganciclovir resistance in patients with acquired immunodeficiency syndrome and cytomegalovirus retinitis: The Cytomegalovirus and Viral Resistance Study Group Report Number 8.

PURPOSE: Cytomegalovirus retinitis is the most common intraocular infection in patients with acquired immunodeficiency syndrome (AIDS). With prolonged suppressive anticytomegalovirus maintenance therapy, resistance occurs in over 25% of patients. We evaluated longitudinal changes in the cytomegalovirus genotype in patients with cytomegalovirus retinitis who developed ganciclovir resistance that was demonstrated in either the blood or urine. METHODS: Patients with AIDS and previously untreated cytomegalovirus retinitis were followed prospectively for the occurrence of resistance while on treatment. Blood and urine specimens were obtained periodically for cytomegalovirus culture according to a predetermined schedule. Positive isolates were tested for phenotypic susceptibility and for mutations in the UL97 and UL54 genes. RESULTS: A mutation conferring resistance to ganciclovir in either the UL97 or UL54 gene was detected in 18 patients. In general, patients with a genotypically resistant virus developed increasing phenotypic resistance over time. There was a suggestion that unless therapy was changed, UL97 mutations tended to persist. In seven of eight patients, the mutations identified in isolates from the blood and urine were identical. In selected patients, there was a suggestion that a mixed population of cytomegalovirus might be present. Progression of the retinitis in an involved eye (15 of 18), contralateral eye retinitis (10 of 11), and extraocular cytomegalovirus disease (5 of 18) occurred commonly among patients with resistant virus. CONCLUSION: Resistance-conferring mutations in the cytomegalovirus genome emerge and may persist when the selective pressure for resistance is maintained. Some patients appear to harbor complex subpopulations of virus with different mutations and different levels of phenotypic resistance. Changes in therapy may result in a shift in virus population and changes in the cytomegalovirus genotype identified.

AIDS-Related Opportunistic Infections↗
PubMed2001

Synthesis of (5alpha)-17-azaandrostan-3-ols and (5alpha)-17-aza-D-homoandrostan-3-ols and their N-acylated derivatives.

Two groups of N-acylated D-azasteroids (4 and 5) were synthesized to explore structure-activity relationships for steroid modulation of GABA(A) receptor function. The target compounds were prepared conveniently from (5alpha)-3-hydroxyandrostan-17-ones (6 and 7) via the intermediate (5alpha)-17-aza-D-homoandrostan-3-ols (14 and 15) or (5alpha)-17-azaandrostan-3-ols (18 and 19) precursors in high overall yields. A Beckmann rearrangement and a Hofmann rearrangement were employed as two key steps in the synthetic sequences.

Androstanols↗
PubMed2001

Normal TCRbeta transcription and recombination in the absence of the Jbeta2-Cbeta2 intronic cis element.

The developmental regulation of antigen receptor gene transcription and recombination are mediated by cis regulatory elements. At the T cell receptor beta chain locus (TCRbeta), two DNase I hypersensitive sites within the Jbeta2-Cbeta2 intron contained binding sites for NF-kappaB and additional nuclear factors and were postulated to be involved in controlling TCRbeta transcription and V(D)J recombination. To test this possibility, we deleted these elements from the mouse genome by homologous recombination and assayed the effect on transcription of both the germline and rearranged TCRbeta locus, and on TCRbeta rearrangement in T and B lymphocytes. We found that TCRbeta transcription and V(D)J recombination and T cell development were normal in these mutant mice. Therefore, the Jbeta2-Cbeta2 intronic elements are dispensable for TCRbeta assembly and function.

Animals↗
PubMed2001

The structure of ionized 1,5 hexadiene in the gas phase.

The structure of ionized 1,5-hexadiene, prepared by charge transfer between 1,5-hexadiene and CS2+*, is examined using energy-resolved collision-induced dissociation (CID). By comparing the product distributions and product appearance curves with those of authentic low-energy C6H10+* ions, it is determined that 1,5-hexadiene cation spontaneously rearranges to cyclohexene cation in the gas-phase. The proposed mechanism for formation of cyclohexene cation in the gas phase is analogous to that determined for this process under matrix isolation conditions, where it proceeds via a Cope rearrangement to the cyclohexane-1,4-diyl cation, followed by isomerization to cyclohexene cation. It is shown that electron ionization (EI) of 1,5-hexadiene gives a different molecular ion than is obtained upon chemical ionization (CI). The energy-resolved CID mass spectrum for the EI product is consistent with what would be obtained for a mixture of low energy ion isomers.

Journal Article↗
PubMed2001

Arsenic in drinking water and skin cancers: cell-type specificity (Taiwan, ROC).

OBJECTIVE: The association between arsenic ingestion and cancer has been documented for more than a century. Previous studies showed that the carcinogenic effects of arsenic on the urinary system are cell-type specific. To evaluate whether this is also true for skin cancers, we conducted an ecological study in 243 townships in Taiwan. METHODS: The arsenic exposure was assessed on the basis of measurement reports from a previous survey, and cases of skin cancer were identified using the information gathered by the National Cancer Registry Program. We analyzed the data by regression models using multiple variables to describe the exposure status, and an urbanization index was also included in the models to adjust for the effects of urbanization. RESULTS: A total of 2369 patients with skin cancer, comprising 1415 men and 954 women, were registered between 1 January 1980 and 31 December 1989. Among the three major cell types of skin cancer, squamous cell carcinoma and basal cell carcinoma appear to be associated with ingestion of arsenic. Such an association was not observed for malignant melanoma. CONCLUSIONS: The results suggested that the carcinogenicity of arsenic on skin is cell-type specific, which is compatible with the findings in previous studies on urinary cancers.

Adult↗
PubMed2001

Tolerance and near-tolerance strategies in monkeys and their application to human renal transplantation.

Studies in non-human primates to evaluate tolerance strategies in organ transplantation have led to innovation in human transplantation. The two strategies we have studied in detail in non-human primates are T-cell depletion by anti-CD3 immunotoxin and co-stimulation blockade. Each of these strategies has been extended into early human trials in renal transplantation. The results of these human and non-human primate studies are summarized. Continued progress in better and safer immunosuppressive methods remains closely linked to research using non-human primates. However, there has not been a one-to-one correspondence between efficacy in the primate and efficacy in humans. Rather, principles can be derived from non-human primate studies that can be extended into human trials with the knowledge that regimens will likely differ in humans compared to non-human primates.

Animals↗
PubMed2001

Cell-surface heparan sulfate is involved in the repulsive guidance activities of Slit2 protein.

Slit proteins are a family of secreted guidance proteins that can repel neuronal migration and axon growth via interaction with their cellular roundabout receptors (Robos). Here it was shown that Slit2-Robo-1 interactions were enhanced by cell-surface heparan sulfate. Removal of heparan sulfate decreased the affinity of Slit for Robo by about threefold. In addition, removal of cell-surface heparan sulfate by heparinase III abolished the chemorepulsive response to Slit2 normally shown by both the migrating neurons and growing axons. These results indicate essential roles for cell-surface heparan sulfate in the repulsive activities of Slit2.

Animals↗
PubMed2001

CD4(+) T cell effectors can become memory cells with high efficiency and without further division.

Whether memory T lymphocytes are derived directly from effector T cells or via a separately controlled pathway has long been debated. Here we present evidence that, after adoptive transfer, a large fraction of in vitro--derived effector CD4(+) T cells have the potential to become memory T cells and that this transition can occur without further division. This data supports a linear pathway from effector to memory cells and suggests that most properties of memory cells are predetermined during effector generation. We suggest, therefore, that evaluation of vaccine efficacy in the induction of memory CD4(+) T cells should focus on the effector stage.

Animals↗
PubMed2001

A distinct expression of CC chemokines by macrophages in nasopharyngeal carcinoma: implication for the intense tumor infiltration by T lymphocytes and macrophages.

Nasopharyngeal carcinoma (NPC) is characterized by harboring Epstein-Barr virus genes in the tumor cells and an intense infiltration of leukocytes in the tumor tissue. These infiltrating cells are mainly composed of T lymphocytes and macrophages. The mechanism of this intense infiltration has long been a puzzle. We attempted to address this issue by studying the expression of CC chemokines, which are responsible for recruiting both T cells and macrophages, by an immunohistochemical approach. In biopsies obtained from nasopharynx of 17 NPC patients that contained tumor cells, expression of macrophage inflammatory protein 1alpha (MIP-1alpha), MIP-1beta, macrophage chemoattractant protein-1 (MCP-1), MCP-2, MCP-3, and RANTES was detected in the tumor-infiltrating cells, with MIP-1alpha and MCP-1 found in nearly all biopsies and the others relatively less frequently. Furthermore, expression of interferon-gamma (IFN-gamma) was also observed in tumor-infiltrating cells. In contrast, CC chemokines and IFN-gamma were rarely expressed in the 13 control biopsies that were either normal or with nonspecific inflammation, and in 4 biopsies from untreated NPC patients that contained no tumor cells. Using an immunofluorescent double-staining method, MIP-1alpha and MCP-1 were identified to be associated with macrophages, and IFN-gamma with T cells. Moreover, expression of CCR2 and CCR5, the receptors for these chemokines, was also detected in the tumor-infiltrating cells. These data indicate that the intense tumor infiltration by T cells and macrophages is a result of active recruitment. It seems possible that the intense infiltration of leukocytes in NPC tumor tissue is initiated by the activated tumor-reactive T cells. T cells migrate into the tumor tissue in an antigen-specific mode, and IFN-gamma secreted from these pioneer T cells activates tissue macrophages to express CC chemokines, especially MIP-1alpha and MCP-1, which consequently recruit more T cells and macrophages into the tumor tissue.

Antibodies, Viral↗
PubMed2001

QSAR modeling of bioconcentration factors in fish based on fragment constants and structural correction factors.

The quantitative structure-activity relationship between the BCF and fragment constant of organic chemicals was studied using a database containing 337 experimental BCF values. The database covered a large variety of chemicals ranging from the very hydrophobic to the very hydrophilic with logKow values between 0.39 and 8.60. The structural features affecting the BCFs were identified and evaluated during a preliminary modeling. A final linear multivariate regression model was derived that was able to account for as much as 98.0% of the variation in the experimental BCF values. The mean absolute error for the final model was 0.315 log-units. In addition, the predictability and robustness of the model was also evaluated.

Animals↗