Prophylactic administration of prostaglandin E1 in liver transplantation: results of a pilot trial.
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Adolescent↗
Biomedical subjects
H Deng
Publications and source records attributed to H Deng.
Cytokines and costimulatory molecules as genetic adjuvants.
DNA vectors expressing an antigen derived from a pathogen or a cancerous cell have been shown, after inoculation into experimental animals, to trigger de novo synthesis of foreign proteins, which induce an immune response. This immune response can be modulated by coinoculation of vectors encoding either cytokines or costimulatory molecules. A variety of cytokines such as granulocyte/macrophage colony-stimulating factor (GM-CSF), IL-2, IL-4, IL-12 and IFN-gamma, as well as the costimulatory molecule B7.1, have been tested to date for their ability to amplify the immune response to genetic vaccines. Although the results obtained thus far clearly show that coadministration of vectors expressing immunomodulatory molecules, such as cytokines, may increase the efficacy of genetic vaccines, this approach is currently considered unsuitable for use in human patients due to the potential side effects of persistent cytokine expression.
Adjuvants, Immunologic↗
Sustainable cutaneous gene delivery.
Durable gene delivery to human skin is necessary for lasting correction of human genetic skin disease. Current cutaneous gene-delivery strategies, however, have achieved only transient gene expression, often only within a small percentage of tissue cells. The recent inability to sustain phenotypic correction of human genetic skin disease due to loss of therapeutic gene expression in regenerated epidermal tissue has highlighted this current limitation. In an effort to surmount this problem, we have generated gene delivery vectors that produce more durable gene delivery in human skin tissue in vivo.
Animals↗
Association analysis of the dopamine D4 gene exon III VNTR and heroin abuse in Chinese subjects.
Although social and cultural influences are clearly important, family, twin and adoption studies indicate that genes contribute significantly to substance abuse. Substance abuse is associated with novelty seeking, a heritable human personality trait which may be influenced by alleles of the dopamine D4 (DRD4) gene exon III VNTR. Consequently Kotler et al analysed the DRD4 VNTR in opiate-dependent subjects from Israel, and found a significant excess of the 7-repeat allele. We have attempted to replicate this finding using a Han Chinese case-control sample of 121 heroin-dependent subjects and 154 normal controls. We found two 7-repeat alleles which occurred exclusively in the patient group, and overall there was an excess of longer alleles, which did not reach significance (chi 2 = 7.04; P = 0.07). When the D4 VNTR was divided into 'long' (5-7 repeats) and 'short' (2-4 repeats), a significant excess of long alleles was observed in the patient group (P = 0.023, one-tailed), with an odds ratio of 2.30 (95% CI 1.07-4.93). We conclude that our findings support the hypothesis that alleles of the DRD4 exon III VNTR are susceptibility factors for heroin abuse.
Adolescent↗
A model of corrective gene transfer in X-linked ichthyosis.
Single gene recessive genetic skin disorders offer attractive prototypes for the development of therapeutic cutaneous gene delivery. We have utilized X-linked ichthyosis (XLI), characterized by loss of function of the steroid sulfatase arylsulfatase C (STS), to develop a model of corrective gene delivery to human skin in vivo. A new retroviral expression vector was produced and utilized to effect STS gene transfer to primary keratinocytes from XLI patients. Transduction was associated with restoration of full-length STS protein expression as well as steroid sulfatase enzymatic activity in proportion to the number of proviral integrations in XLI cells. Transduced and uncorrected XLI keratinocytes, along with normal controls, were then grafted onto immunodeficient mice to regenerate full thickness human epidermis. Unmodified XLI keratinocytes regenerated a hyperkeratotic epidermis lacking STS expression with defective skin barrier function, effectively recapitulating the human disease in vivo. Transduced XLI keratinocytes from the same patients, however, regenerated epidermis histologically indistinguishable from that formed by keratinocytes from patients with normal skin. Transduced XLI epidermis demonstrated STS expression in vivo by immunostaining as well as a normalization of histologic appearance at 5 weeks post-grafting. In addition, transduced XLI epidermis demonstrated a return of barrier function parameters to normal. These findings demonstrate corrective gene delivery in human XLI patient skin tissue at both molecular and functional levels and provide a model of human cutaneous gene therapy.
Animals↗
Catechol-O-methyltransferase Val158Met polymorphism: frequency analysis in Han Chinese subjects and allelic association of the low activity allele with bipolar affective disorder.
Catechol-O-methyltransferase catalyses the O-methylation of biologically active or toxic catechols and is a major component of the metabolism of drugs and neurotransmitters such as L-dopa, noradrenaline, adrenaline, and dopamine. Human catechol-O-methyltransferase activity is an autosomal partially dominant trait and is strongly associated with a valine to methionine substitution at codon 158 of the protein. About 25% of Caucasians have low activity, 50% intermediate activity and 25% high activity as determined by either phenotypic or genotypic measurement. In black populations, the low activity allele (Met158; COMTL) is less frequent with about 7% being homozygous. Using a PCR based genotyping assay, we report that the Met158 allele is also less frequent in normal Han Chinese subjects with about 3% of the population being homozygous. Because of its role in catecholamine metabolism and several lines of evidence pointing to a locus for psychosis near the COMT gene on chromosome 22q11, we have analysed the COMT Val158Met polymorphism as a candidate susceptibility factor for bipolar affective disorder. We report an association between bipolar affective disorder and the Met158 allele (p = 0.004) and genotype (p = 0.01) in 93 affected Chinese subjects and 98 controls. We hypothesize that either the low activity allele of catechol-O-methyltransferase is a risk factor for bipolar affective disorder in Chinese populations or is in linkage disequilibrium with a nearby susceptibility gene or polymorphism.
Bipolar Disorder↗
A resonance Raman study of the C=C stretch modes in bovine and octopus visual pigments with isotopically labeled retinal chromophores.
Previous resonance Raman spectroscopic studies of bovine and octopus rhodopsin and bathorhodopsin in the C-C stretch fingerprint region have shown drastically different spectral patterns, which suggest different chromophore-protein interactions. We have extended our resonance Raman studies of bovine and octopus pigments to the C=C stretch region in order to reveal a more detailed picture about the difference in retinal-protein interactions between these two pigments. The C=C stretch motions of the protonated retinal Schiff base are strongly coupled to form highly delocalized ethylenic modes located in the 1500 to 1650 cm-1 spectral region. In order to decouple these vibrations, a series of 11,12-D2-labeled retinals, with additional 13C labeling at C8, C10, C11 and C14, respectively, are used to determine the difference of specific C=C stretch modes between bovine and octopus pigments. Our results show that the C9=C10 and C13=C14 stretch mode are about 20 cm-1 lower in the Raman spectrum of octopus bathorhodopsin than in bovine bathorhodopsin, while the other C=C stretch modes in these two bathorhodopsins are similar. In contrast, only the C9=C10 stretch mode in octopus rhodopsin is about 10 cm-1 lower than in bovine rhodopsin, while other C=C stretches are similar.
Animals↗
Coreceptor usage of primary human immunodeficiency virus type 1 isolates varies according to biological phenotype.
The biological phenotype of primary human immunodeficiency virus type 1 (HIV-1) isolates varies according to the severity of the HIV infection. Here we show that the two previously described groups of rapid/high, syncytium-inducing (SI) and slow/low, non-syncytium-inducing (NSI) isolates are distinguished by their ability to utilize different chemokine receptors for entry into target cells. Recent studies have identified the C-X-C chemokine receptor CXCR4 (also named fusin or Lestr) and the C-C chemokine receptor CCR5 as the principal entry cofactors for T-cell-line-tropic and non-T-cell-line-tropic HIV-1, respectively. Using U87.CD4 glioma cell lines, stably expressing the chemokine receptor CCR1, CCR2b, CCR3, CCR5, or CXCR4, we have tested chemokine receptor specificity for a panel of genetically diverse envelope glycoprotein genes cloned from primary HIV-1 isolates and have found that receptor usage was closely associated with the biological phenotype of the virus isolate but not the genetic subtype. We have also analyzed a panel of 36 well-characterized primary HIV-1 isolates for syncytium induction and replication in the same series of cell lines. Infection by slow/low viruses was restricted to cells expressing CCR5, whereas rapid/high viruses could use a variety of chemokine receptors. In addition to the regular use of CXCR4, many rapid/high viruses used CCR5 and some also used CCR3 and CCR2b. Progressive HIV-1 infection is characterized by the emergence of viruses resistant to inhibition by beta-chemokines, which corresponded to changes in coreceptor usage. The broadening of the host range may even enable the use of uncharacterized coreceptors, in that two isolates from immunodeficient patients infected the parental U87.CD4 cell line lacking any engineered coreceptor. Two primary isolates with multiple coreceptor usage were shown to consist of mixed populations, one with a narrow host range using CCR5 only and the other with a broad host range using CCR3, CCR5, or CXCR4, similar to the original population. The results show that all 36 primary HIV-1 isolates induce syncytia, provided that target cells carry the particular coreceptor required by the virus.
Acquired Immunodeficiency Syndrome↗
Identification and analysis of a lytic-phase origin of DNA replication in human herpesvirus 7.
Human herpesvirus 7 (HHV-7) DNA sequences colinear with the HHV-6 lytic-phase origin of DNA replication (oriLyt) were amplified by PCR. Plasmid constructs containing these sequences were replicated in HHV-7-infected cord blood mononuclear cells but not in HHV-6-infected cells. In contrast, plasmids bearing HHV-6 oriLyt were replicated in both HHV-6- and HHV-7-infected cells. Finally, the minimal HHV-7 DNA element necessary for replicator activity was mapped to a 600-bp region which contains two sites with high homology to the consensus binding site for the HHV-6 origin binding protein. At least one of these binding sites was shown to be essential for replicator function of HHV-7 oriLyt.
Base Sequence↗
Envelope glycoproteins from human immunodeficiency virus types 1 and 2 and simian immunodeficiency virus can use human CCR5 as a coreceptor for viral entry and make direct CD4-dependent interactions with this chemokine receptor.
Several members of the chemokine receptor family have recently been identified as coreceptors, with CD4, for entry of human immunodeficiency virus type 1 (HIV-1) into target cells. In this report, we show that the envelope glycoproteins of several strains of HIV-2 and simian immunodeficiency virus (SIV) employ the same chemokine receptors for infection. Envelope glycoproteins from HIV-2 use CCR5 or CXCR4, while those from several strains of SIV use CCR5. Our data indicate also that some viral envelopes can use more than one coreceptor for entry and suggest that some of these coreceptors remain to be identified. To further understand how different envelope molecules use CCR5 as an entry cofactor, we show that soluble purified envelope glycoproteins (SU component) from CCR5-tropic HIV-1, HIV-2, and SIV can compete for binding of iodinated chemokine to CCR5. The competition is dependent on binding of the SU glycoprotein to cell surface CD4 and implies a direct interaction between envelope glycoproteins and CCR5. This interaction is specific since it is not observed with SU glycoprotein from a CXCR4-tropic virus or with a chemokine receptor that is not competent for viral entry (CCR1). For HIV-1, the interaction can be inhibited by antibodies specific for the V3 loop of SU. Soluble CD4 was found to potentiate binding of the HIV-2 ST and SIVmac239 envelope glycoproteins to CCR5, suggesting that a CD4-induced conformational change in SU is required for subsequent binding to CCR5. These data suggest a common fundamental mechanism by which structurally diverse HIV-1, HIV-2, and SIV envelope glycoproteins interact with CD4 and CCR5 to mediate viral entry.
3T3 Cells↗
Isolation and characterization of a new chromosome 8q24.1 band-specific microsatellite polymorphism.
A clone, containing a 24-dinucleotide (CA)-repeat sequence, was isolated from chromosome 8q24.1 band-specific pUC19 library. It was localized to target chromosome using human-rodent hybrid cell panel. Eleven alleles were estimated from 56 unrelated individuals and the heterozygosity reaches 0.835. Linkage analysis of 11 Chinese pedigrees showed significant evidence for linkage of this new marker to three dinucleotide repeat markers at 8q23-24.1 region, with the most likely position of the marker between D8S85 and D8S199.
Alleles↗
[Significance of detection of inflammatory samples in the sputum of patients with asthma].
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Asthma↗
[The study on chemical composition and crystalline structure of hypoplastic primary dental enamel].
The present study, firstly, analyzed chemical composition of hypoplastic primary teeth by electron probe analyzer and compared the hypoplastic part with the normal part in the same tooth; secondly, by X-ray diffraction analyzer, studied the hypoplastic dental enamel and the normal dental enamel, and compared the crystalline structure between different dental enamel and with that of the hydroxyapatite. The aim was to find out any change of crystalline structure. Two exfoliated hypoplastic deciduous anterior teeth were used for the electron probe study. The normal part of each tooth served as control. Determinations of weight percentage (wt%) were made for P, Al, Mg, Ca, Mn, Fe, Zn, Sr, Na, K and F. Four exfoliated hypoplastic deciduous anterior teeth and eight exfoliated normal deciduous anterior teeth were used for the X-ray diffraction study. We found by X-ray diffraction that the length of the alpha-axis of enamel crystallite and the distance of lattice plane (corresponding 300) were increased in defective enamel and could be associated with the increased content of magnesium detected by electron probe. Thus, the present study demonstrated that there were both quantity and quality changes in the enamel hypoplasia lesion, which may increase the susceptibility of the defective teeth to caries.
Calcium↗
[Isolation of band-specific (CA)n microsatellites from human chromosome 8q24.1].
Fourty eight recombinant plasmids containing CA repeats were isolated from human chromosome 8q24.1 band-specific pUC19 library. Among them, inserted DNA fragments from 12 plasmids were sequenced, and one new highly polymorphic (CA)n microsatellite was obtained (coding: D8S7F). It contained 11 alleles. The estimated heterozygosity reached 0.84 and 0.83 among Chinese Han Nationality people and American Anglo-Saxons respectively. It was assigned to chromosome 8 by using a human-rodent hybrid cell panel.
Base Sequence↗
[Effect of glucocorticoid on CD4 T-lymphocyte and eosinophil activation in asthmatics].
To study the influence of oral glucocorticoid on CD4 T-lymphocyte and eosinophil activation in the asthmatics, we collected the serum samples from 14 patients who required oarl glucocorticoid therapy for moderate to severe disease exacerbations and measured the serum interleukin (IL)-5, eosinophil cationic protein (ECP) levels before and after one week with prednisone (20 mg/d) by enzyme-linked immunosorbent assay. The results revealed that after oral prednisone therapy, the serum IL-5, ECP levels and the numbers of peripheral blood eosinophils decreased, whereas the lung function significantly improved. It is suggested that glucocorticoids might exert antiasthma effect of by inhibiting CD4 T-lymphocyte activation and cytokine (e.g., IL-5) secretion.
Adolescent↗
[A study on neurotoxicity of acrylamide and glycidamide].
Glycidamide (GA) is an epoxide metabolite of acrylamide (AA). Neurotoxicity of both GA and AA was compared by their performance in behavioral, neuro-biochemical and neuropathological studies. Male rats were injected peritoneally with AA (25 or 50 mg/kg) or GA (50 or 100 mg/kg) once daily for eight days. Results showed that toxic effects of AA were greater than those of GA in wheel rotation test, hind limb splay test, and activities of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in peripheral nerves in rats. Results of neuropathological examinations in experimental rats also provided evidence that AA could cause damage to peripheral nerves, but GA did not. It indicated that nerve tissue was more vulnerable to AA than to GA. Also, it suggested that neurotoxic effects of AA was caused by itself, and influenced less by its metabolite GA.
Acrylamides↗
[Clinical application of myocardial perfusion imaging with 99mTc-MIBI SPECT in the diagnosis of coronary artery disease].
Myocardial perfusion imaging with 99mTc-MIBI was studied in 80 patients with coronary artery disease (CAD), 29 cases of normal controls and 37 cases of noncoronary heart diseases. The perfusion imaging was analysed both by qualitative and quantitative methods. The results revealed that the diagnostic sensitivity, specificity and accuracy for CAD were 91.5%, 83.8%, and 88.5% respectively by qualitativ method, and were 88.1%, 94.6% and 90.6% respectively by quantitative method. The diagnostic sensitivity of electrocardiogram (ECG) was 69.5%. Fourteen cases with the narrowing of coronary artery > 50% shown by coronary angiography also had abnormal myocardial perfusion imaging. It suggests that analysis of perfusion imaging by quantitative method in detecting CAD is superior than qualitative method and ECG.
Adult↗
A resonance Raman study of the C=N configurations of octopus rhodopsin, bathorhodopsin, and isorhodopsin.
The resonance Raman spectra of octopus rhodopsin, bathorhodopsin, and isorhodopsin at 120 K have been obtained as well as those of pigments regenerated with isotopically labeled retinals near the C14-C15 bond. Deuteration of the Schiff base nitrogen induces relatively large changes in the C-C stretch region between 1100 and 1300 cm-1, including a large frequency shift of the C14-C15 stretch mode located at 1206-1227 cm-1 in the three octopus species, as revealed by the Raman spectra of their 14,15-(13)C2 derivatives. Such results are different compared to those of the bovine pigments, in which no significant frequency shift of the C14-C15 stretch mode was observed upon Schiff base N deuteration. In an earlier Raman study of a Schiff base model compound which contained only one single bond adjacent to two double bonds, we have found that the stretch mode of this C-C single bond at 1232 cm-1 shifts up by 15 cm-1 and its intensity is also greatly reduced upon Schiff base N deuteration when the C=N configuration is anti [Deng et al., (1994) J. Phys. Chem. 98, 4776-4779]. The same study has also shown that when the C=N configuration is syn, the C-C stretch mode should be at about 1150 cm-1. Since the C14-C15 stretch mode frequency is relatively high in the spectra of octopus rhodopsin and bathorhodopsin (> 1200 cm-1) and since the normal mode pattern near the Schiff base is similar to the model, we suggest that the C=N configuration in these two species is anti. The different responses of the C14-C15 stretch mode to the Schiff base nitrogen deuteration in bovine and octopus pigments are due to the fact that the coupled C14-C15 stretch and the C12-C13 stretch motions in the model compound or in bovine rhodopsin are altered in octopus rhodopsin so that the stretch motion of the C14-15 bond is more localized, similar to the C-C stretch motion in the small Schiff base model compound. In clear contrast with the bovine rhodopsin Raman spectrum, which is very similar to that for the 11-cis-retinal Schiff base, the drastically different octopus rhodopsin spectrum indicates large protein perturbations on the C11=C12-C13 moiety, either by steric or by electrostatic interactions. Further studies are required to determine if such spectral differences indicate a difference of the energy conversion mechanism in the primary photochemical event of these two pigments.
Animals↗