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Biomedical subjects

J Hu

Publications and source records attributed to J Hu.

At least 235 records · Page 13Linked to original sources
PubMed2000

Transplantation and growth characteristics of human fetal lymph node in immunodeficient mice.

OBJECTIVE: The lymph node is an integral component of the immune system and the major site of antigen-dependent lymphocyte proliferation and differentiation. Development of animal models possessing functional primary human lymph nodes will have a significant impact on research in lymphopoiesis and immune response. To date, successful transplantation of primary human lymph nodes in rodents has not yet been reported. This work was undertaken to develop a reliable methodology to engraft primary human fetal lymph nodes in immunodeficient mice. MATERIALS AND METHODS: Three different sets of parameters, including three different transplantation sites in the mice, two different strains of immunodeficient mice, and two different preconditioning regimens, were evaluated. The growth characteristics of the implanted primary human fetal lymph nodes were examined 3 months after transplantation by histologic, immunocytochemical, and flow cytometric methods. RESULTS: Transplantation of primary human fetal lymph nodes into subcutaneous pouches in the ears in severe combined immunodeficiency (SCID) mice preconditioned with etoposide reproducibly give rise to >80% engraftment. The engrafted primary human fetal lymph nodes undergo massive growth (>200-fold) and retain the same histology and cellular composition as fresh human fetal lymph nodes from the same donors. CONCLUSIONS: We report, for the first time, the development of a reliable methodology to successfully engraft human fetal lymph node in SCID mice. The engrafted human lymph nodes are visible and accessible to experimental manipulations. This SCID-hu mouse model with human lymph node should provide a physiologically relevant system to investigate lymphopoiesis, immunologic response, and virus-mediated immunosuppression.

Animals↗
PubMed2000

Universal learning network and its application to chaos control.

Universal Learning Networks (ULNs) are proposed and their application to chaos control is discussed. ULNs provide a generalized framework to model and control complex systems. They consist of a number of inter-connected nodes where the nodes may have any continuously differentiable nonlinear functions in them and each pair of nodes can be connected by multiple branches with arbitrary time delays. Therefore, physical systems, which can be described by differential or difference equations and also their controllers, can be modeled in a unified way, and so ULNs may form a super set of neural networks and fuzzy neural networks. In order to optimize the ULNs, a generalized learning algorithm is derived, in which both the first order derivatives (gradients) and the higher order derivatives are incorporated. The derivatives are calculated by using forward or backward propagation schemes. These algorithms for calculating the derivatives are extended versions of Back Propagation Through Time (BPTT) and Real Time Recurrent Learning (RTRL) of Williams in the sense that generalized node functions, generalized network connections with multi-branch of arbitrary time delays, generalized criterion functions and higher order derivatives can be deal with. As an application of ULNs, a chaos control method using maximum Lyapunov exponent of ULNs is proposed. Maximum Lyapunov exponent of ULNs can be formulated by using higher order derivatives of ULNs, and the parameters of ULNs can be adjusted so that the maximum Lyapunov exponent approaches the target value. From the simulation results, it has been shown that a fully connected ULN with three nodes is able to display chaotic behaviors.

Artificial Intelligence↗
PubMed2000

The rice R gene family: two distinct subfamilies containing several miniature inverted-repeat transposable elements.

The R and B genes of maize regulate the anthocyanin biosynthetic pathway and constitute a small gene family whose evolution has been shaped by polyploidization and transposable element activity. To compare the evolution of regulatory genes in the distinct but related genomes of rice and maize, we previously isolated two R homologues from rice (Oryza sativa). The Ra1 gene on chromosome 4 can activate the anthocyanin pathway, whereas the Rb gene, of undetermined function, maps to chromosome 1. In this study, rice R genes have been further characterized. First, we found that an Rb cDNA can induce pigmentation in maize suspension cells. Second, another rice R homologue (Ra2) was identified that is more closely related to Ra1 than to Rb. Domesticated rice and its wild relatives harbor multiple Ra-like and Rb-like genes despite the fact that rice is a true diploid with the smallest genome of all the grass species analyzed to date. Finally, several miniature inverted-repeat transposable elements (MITEs) were found in R family members. Their possible role in hastening the divergence of R genes is discussed.

Amino Acid Sequence↗
PubMed2000

Passive and active smoking and breast cancer risk in Canada, 1994-97.

BACKGROUND: Studies comparing ever smokers with never smokers have found little increase in breast cancer risk. However, the five published studies examining passive smoking and breast cancer have all suggested associations with both passive and active smoking, particularly premenopausal risk. METHODS: We analyzed data collected through the Canadian National Enhanced Cancer Surveillance System, from 805 premenopausal and 1512 postmenopausal women with newly diagnosed (incident), histologically confirmed, primary breast cancer and 2438 population controls. The mailed questionnaire included questions on breast cancer risk factors and a lifetime residential and occupational history of exposure to passive smoking. RESULTS: Among premenopausal women who were never active smokers, regular exposure to passive smoke was associated with an adjusted breast cancer odds ratio (OR) of 2.3 (95% confidence interval [CI] 1.2-4.6). Passive exposure showed a strong dose-response trend (test for trend p = 0.0007) with an OR of 2.9 (95% CI 1.3-6.6) for more than 35 years of passive residential and/or occupational exposure. When premenopausal women who had ever actively smoked were compared with women never regularly exposed to passive or active smoke, the adjusted OR for breast cancer was also 2.3 (95% CI 1.2-4.5). Among postmenopausal women who were never-active smokers, regular exposure to passive smoke was associated with an adjusted breast cancer OR of 1.2 (95% CI 0.8-1.8) and an OR of 1.4 (95% CI 0.9-2.3) for the most highly exposed quartile of women. The adjusted OR for postmenopausal breast cancer risk for ever-active smokers compared with women never regularly exposed to passive or active smoke was 1.5 (95% CI 1.0-2.3). Statistically significant dose-response relationships were observed with increasing years of smoking, increasing pack-years and decreasing years since quitting. Women with 35 or more years of smoking had an adjusted OR of 1.7 (95% CI 1.1-2.7). CONCLUSIONS: Active and passive smoking may be associated with increased breast cancer risk, particularly premenopausal risk.

Adult↗
PubMed2000

Novel pathophysiological role of classical chemotactic peptide receptors and their communications with chemokine receptors.

The bacterial N-formylpeptides, such as N-formyl-Met-Leu-Phe (fMLF), are some of the first identified and most potent chemoattractants for phagocytic leukocytes. Two fMLF receptors, the high affinity formyl peptide receptor (FPR) and its low affinity variant FPR-like 1 (FPRL1), belong to the seven-transmembrane, Gi protein-coupled receptor superfamily which also includes chemokine receptors. Despite their reaction with bacterial chemotactic peptides, the physiological role of these receptors in humans remains unclear. Our recent studies have identified novel exogenous as well as host-derived agonists for FPR and FPRL1. Furthermore, activation of these receptors by their agonists results in desensitization of the receptors for other chemoattractants, including two chemokine receptors, CCR5 and CXCR4, which serve as major co-receptors for HIV-1. These results suggest that FPR and FPRL1 may play important roles not only in host defense and immunological responses but also in the fine tuning of cell activation in the presence of multiple stimuli.

Animals↗
PubMed2000

Inhibition of cell proliferation in HCC-9204 hepatoma cells by a c-myc specific ribozyme.

A ribozyme (RZ) gene targeting c-myc mRNA was synthesized and cloned. Cleavage reaction showed that cleavage of the RZ was efficient and specific. The RZ gene-containing retrovirus vector pDOR-RZ was transfected into HCC-9204 hepatoma cells, which constitutively express high levels of c-myc using Lipofectamine. Positively transfected cells were selected using G418. In situ hybridization showed that both pDOR-RZ and pDOR vectors had been integrated into the chromosome of HCC-9204 cells. Dot blot hybridization indicated that expression of the RZ was only evident in pDOR-RZ-transfected HCC-9204 cells. Avidin-biotin complex enzyme-linked immunosorbent assay showed that c-myc expression was down-regulated. Chromatin aggregation into compact masses, cytoplasmic vacuole degeneration, and blurring of cytoplasm structure were observed by transmission electron microscopy in HCC-9204-RZ cells. These results suggest that the use of a c-myc mRNA cleaving enzyme could be most effective in tumor cells that are highly proliferative and constitutively express high levels of c-myc.

Carcinoma, Hepatocellular↗
PubMed2000

Study of the electrochemical behavior of mitoxantrone and its determination at a Co-C modified ultramicroelectrode.

In 0.005 mol dm-3 Tris-0.05 mol dm-3 NaCl buffer solution (pH 7.10), the electrochemical behavior of mitoxantrone was studied by linear-sweep voltammetry and cyclic voltammetry at a Co-carbon fiber ion implantation modified ultramicroelectrode. A sensitive reduction peak was obtained. The peak potential was -0.798 V (vs. SCE), the peak current was proportional to the concentration of mitoxantrone over the range of 2.0 x 10(-7)-6.0 x 10(6) mol dm-3 and the detection limit was 4.2 x 10(-8) mol dm-3. This method was applied to the direct determination of mitoxantrone in urine. Recoveries were in the range 95.4-105.8%. The reduction process was quasi-reversible with absorptive characteristics at a Co-C ultramicroelectrode. According to Laviron's theory, the electrode reaction rate constant ks and the electron transfer alpha of mitoxantrone were 4.4 s-1 and 0.48, respectively. The composition and depth distribution of elements on the surface of the Co-C ultramicroelectrode were determined by Auger electron spectroscopy. The experiments showed that Co was implanted into the surface of the carbon fiber, and the Co-C ultramicroelectrode had good stability and reproducibility.

Journal Article↗
PubMed2000

Central neurocytomas are genetically distinct from oligodendrogliomas and neuroblastomas.

AIMS: Central neurocytoma is a rare central nervous system tumour typically found in the lateral ventricles and at the septum pellucidum. Histologically, it resembles oligodendrogliomas and yet ultrastructurally, it shows neuronal differentiation. Its molecular oncogenesis is not known. The aim of this study was to examine whether major genetic events found in oligodendrogliomas and neuronal tumours, namely allelic deletions of chromosomes 1p and 19q and N-myc amplification, can be found in central neurocytomas. As there was one report describing gain of chromosome 7 in central neurocytomas, we also examined epidermal growth factor receptor (EGFR) amplification, as the EGFR gene is located at chromosome 7p. METHODS AND RESULTS: Nine central neurocytomas and matched blood samples were examined for loss of heterozygosity (LOH) of 1p and 19q13.2-13.4 with 23 finely mapped microsatellite markers. N-myc amplification was studied by fluorescence in-situ hybridization using paraffin-embedded sections. EGFR amplification was tested for by differential PCR. Six of nine (67%) tumours showed LOH at one or more loci at 1p and 5/9 (56%) of cases showed LOH at 19q. However, common regions of deletion cannot be identified. The majority of informative markers are retained at 1p (84%) and 19q (86%). Only one tumour showed amplification of N-myc and none of the cases showed amplification of EGFR. CONCLUSION: Central neurocytomas are genetically distinct from oligodendrogliomas, and chromosomes 1p and 19q probably do not play an important role in their pathogenesis. N-myc and EGFR amplification are rare.

Adolescent↗
PubMed2000

Leukemia inhibitory factor induces epidermal hyperplasia in patients with amyotrophic lateral sclerosis.

We investigated the biochemical and morphologic alteration in skin of amyotrophic lateral sclerosis patients. We found an obvious high expression of leukemia inhibitory factor and distinct epidermal hyperplasia in the skin of amyotrophic lateral sclerosis patients compared with disease controls. The thickness and cell density, as well as the leukemia inhibitory factor immunostain density, of the epidermis in amyotrophic lateral sclerosis patients correlated positively with duration of illness. The striking fact was the significant epidermal hyperplasia correlating with leukemia inhibitory factor expression in amyotrophic lateral sclerosis patients (r = 0.94, p < 0.001). In vitro experiments revealed that leukemia inhibitory factor stimulated keratinocyte proliferation in primary keratinocyte culture and induced epidermal hyperplasia in skin organ culture. These findings lead to the hypothesis that a high expression of leukemia inhibitory factor is closely associated with epidermal hyperplasia in amyotrophic lateral sclerosis patients.

Adult↗
PubMed2000

Terpenoids and flavonoids from Artemisia species.

A phytochemical reinvestigation of the aerial parts of Artemisia sieversiana gave a new guaianolide and two known flavones (chrysosplenetin and 5-hydroxy-3',4',6,7-tetramethoxyflavone). Antifungal fractions derived from the chloroform extract of A. annua afforded two cadinane derivatives (arteannuin B and artemisinin), oleanolic acid, beta-sitosterol, stigmasterol, and the four flavones artemetin, bonanzin, eupalitin and chrysosplenetin. Their structures were elucidated by spectral methods. All isolates from the two species were tested in vitro for antifungal activity. Arteannuin B, a main sesquiterpenoid in A. annua, showed antifungal activity against one human (Candida albicans, MIC: 100 micrograms/ml) and four plant pathogenic fungi (Gaeumannomyces graminis var. tritici, Rhizoctonia cerealis, Gerlachia nivalis and Verticillium dahliae, MICs: 150, 100, 150 and 100 micrograms/ml, respectively) whereas others showed no antifungal activity. The MIC value of ketoconazole to C. albicans was 1.0 microgram/ml, and those of triadimefon to G. graminis var. tritici and R. cerealis 150 and 100 micrograms/ml.

Antifungal Agents↗
PubMed2000

Phenylpropanes from Acorus tatarinowii.

In addition to a number of known compounds, four new phenylpropanes isoacoramone, (cis) epoxyasarone, (threo) 1',2'-dihydroxyasarone and (erythro) 1',2'-dihydroxyasarone were obtained from the roots of Acorus tatarinowii ("Shi-Chang-Pu" in Chinese). The later two isomers were obtained as a mixture. However, all the chemical shifts of the protons and carbons for these two components were assigned by 1D- and 2D-NMR techniques.

Magnetic Resonance Spectroscopy↗
PubMed2000

Triterpenoids, p-coumaric acid esters and flavonoids from Artemisia igniaria.

Twenty-eight components were detected from the extract of Artemisia igniaria, which included four triterpenoids, eight p-coumaric acid long chain alkyl esters, seven flavonoids and nine common plant constituents. Their structures were determined by spectroscopic methods. This is the first recorded instance of beta-glutinanol and cis-p-coumaric acid eicosanyl ester occurring in nature.

Artemisia↗
PubMed2000

Parental cigarette smoking, hard liquor consumption and the risk of childhood brain tumors--a case-control study in northeast China.

In this study we examine the effect of parents' lifestyles on the risk of childhood brain tumors. Parents of 82 children newly diagnosed with primary malignant brain tumors and 246 individually matched hospital controls were interviewed in the hospital wards between September 1991 and December 1996. Data were collected on socioeconomic status, parental lifestyle prior to and during the pregnancy, and family history. Odds ratios and 95% confidence intervals were derived through conditional logistic regression. The risk of childhood brain tumors was associated with paternal use of hard liquor prior to the pregnancy: the odds ratios were 3.72 (95% CI = 1.91-7.26) for < or = 15 years of hard liquor consumption and 4.06 (95% CI = 1.09-15.21) for > or = 16 years of hard liquor consumption compared with never consuming hard liquor (test for trend p = 0.0001); the odds ratios increased with increasing lifetime hard liquor consumption. There is little evidence to support an association between childhood brain tumors and parents' smoking prior to or during pregnancy.

Adolescent↗
PubMed2000

Preliminary study on the cleavage of fusion protein GST-CMIV with palladium(II) complex.

A novel method for post-treatment of gene-engineered proteins is reported. A coden of Cys-His unit is introduced into the N-terminal of cecropin CMIV by using PCR. The gene is expressed in E. coli fused with GST. After purification, the fusion protein is cleaved by [Pd(en)(H2O)2]2+ at the His-Arg bond and the cecropin CMIV with antibacterial activity is obtained. The preliminary results held some promise of success for application of the palladium(II) complex as cleavage agent for the production of peptide drugs from gene-engineering fusion proteins.

Anti-Bacterial Agents↗
PubMed2000

Beam alignment and related problems of spherical aberration corrected high-resolution TEM images.

For spherical aberration corrected transmission electron microscopes recently developed, the Scherzer resolution in proportion to C(s) 1/4 lambda 3/4 is still inevitably limited by the influence of some other electron optical factors, such as chromatic aberration coefficient of objective lens (C(c)), beam divergence and alignment, incident electron energy spread (deltaE), and the instability of accelerating voltage (deltaV) and of lens current (deltaI). Depending on the image resolution guaranteed by C(s) correction, the defocus spread caused by C(c), deltaV, deltaI and deltaE would need to be reduced. The effect of beam alignment as a phase shift in contrast transfer function is also studied for the C(s) corrected microscopes with different values of C(s), defocus and spatial frequency. There is a relationship between the phase shift and defocus that allows us to find a series of 'alignment-free' focal conditions. A triangular relation among C(s), defocus and lattice spacing is established for proper image contrast and 'alignment-free' imaging with the C(s) corrected microscope.

Journal Article↗
PubMed2000

Simian immunodeficiency virus rapidly penetrates the cervicovaginal mucosa after intravaginal inoculation and infects intraepithelial dendritic cells.

Despite recent insights into mucosal human immunodeficiency virus (HIV) transmission, the route used by primate lentiviruses to traverse the stratified squamous epithelium of mucosal surfaces remains undefined. To determine if dendritic cells (DC) are used by primate lentiviruses to traverse the epithelial barrier of the genital tract, rhesus macaques were intravaginally exposed to cell-free simian immunodeficiency virus SIVmac251. We examined formalin-fixed tissues and HLA-DR(+)-enriched cell suspensions to identify the cells containing SIV RNA in the genital tract and draining lymph nodes within the first 24 h of infection. Using SIV-specific fluorescent in situ hybridization combined with immunofluorescent antibody labeling of lineage-specific cell markers, numerous SIV RNA(+) DC were documented in cell suspensions from the vaginal epithelium 18 h after vaginal inoculation. In addition, we determined the minimum time that the SIV inoculum must remain in contact with the genital mucosa for the virus to move from the vaginal lumen into the mucosa. We now show that SIV enters the vaginal mucosa within 60 min of intravaginal exposure, infecting primarily intraepithelial DC and that SIV-infected cells are located in draining lymph nodes within 18 h of intravaginal SIV exposure. The speed with which primate lentiviruses penetrate mucosal surfaces, infect DC, and disseminate to draining lymph nodes poses a serious challenge to HIV vaccine development.

Administration, Intravaginal↗
PubMed2000

In vitro reconstitution of a functional duck hepatitis B virus reverse transcriptase: posttranslational activation by Hsp90.

Reverse transcription in hepatitis B viruses is initiated through a unique protein priming mechanism whereby the viral reverse transcriptase (RT) first assembles into a ribonucleoprotein (RNP) complex with its RNA template and then initiates DNA synthesis de novo using the RT itself as a protein primer. RNP formation and protein priming require the assistance of host cell factors, including the molecular chaperone heat shock protein 90 (Hsp90). To better understand the mechanism of RT activation by Hsp90, we have now mapped the minimal RT sequences of the duck hepatitis B virus that are required for chaperone binding, RNP formation, and protein priming. Furthermore, we have reconstituted in vitro both RNP formation and protein priming using purified RT proteins and host factors. Our results show that (i) Hsp90 recognizes two independent domains of the RT, both of which are necessary for RNP formation and protein priming; (ii) Hsp90 function is required not only to establish, but also to maintain, the RT in a state competent for RNA binding; and (iii) Hsp90 is not required during RT synthesis and can activate the RT posttranslationally. Based on these findings, we propose a model for Hsp90 function whereby the chaperone acts as an active interdomain bridge to bring the two RT domains into a poised but labile conformation competent for RNP formation. It is anticipated that the reconstitution system established here will facilitate the isolation of additional host factors required for RT functions and further elucidation of the mechanisms of RT activation.

HSP90 Heat-Shock Proteins↗