PubMed Health⌕ Search

Biomedical subjects

D Zhang

Publications and source records attributed to D Zhang.

At least 577 records · Page 32Linked to original sources
PubMed1994

Targeting of human immunodeficiency virus-infected cells by CD8+ T lymphocytes armed with universal T-cell receptors.

We have developed an immunotherapeutic approach with potential application in the treatment of viral and malignant disease. We show that primary CD8+ T cells isolated from peripheral blood can be genetically modified by retroviral transduction to express high levels of universal (major histocompatibility complex-unrestricted) chimeric T-cell receptors specific for human immunodeficiency virus (HIV) antigens. Two classes of HIV-specific URs in which the antigen-binding domain is comprised of either CD4 or a single-chain antibody are capable of activating a number of T-cell effector functions in response to target cells, including cytolysis, in a highly sensitive and specific manner. Importantly, we have addressed a number of issues which, although particularly relevant to the clinical application of this approach in the treatment of HIV infection, may also impact on the potential of UR immunotherapy for other disease targets. The UR immunotherapeutic system is particularly suited for evaluation in the clinical setting.

Animals↗
PubMed1994

Structural interaction of natural and synthetic inhibitors with the venom metalloproteinase, atrolysin C (form d).

The structure of the metalloproteinase and hemorrhagic toxin atrolysin C form d (EC 3.4.24.42), from the venom of the western diamondback rattlesnake Crotalus atrox, has been determined to atomic resolution by x-ray crystallographic methods. This study illuminates the nature of inhibitor binding with natural (< Glu-Asn-Trp, where < Glu is pyroglutamic acid) and synthetic (SCH 47890) ligands. The primary specificity pocket is exceptionally deep; the nature of inhibitor and productive substrate binding is discussed. Insights gained from the study of these complexes facilitate the design of potential drugs to treat diseases where matrix metalloproteinases have been implicated, e.g., arthritis and tumor metastasis.

Amides↗
PubMed1994

A modified nonradioactive method for northern blot analysis.

In this report we use several previously described methods, in novel combination, to establish a sensitive and flexible nonradioactive method. First, we prepared single-stranded digoxigenin-labeled probes using a high-efficiency polymerase chain reaction (PCR) method (4). For detection of RNA, blots were hybridized with probes containing digoxigenin and then incubated with alkaline phosphatase-conjugated anti-digoxigenin antibody. Bound probe was rapidly detected with X-ray film using localized light emission from the reaction of alkaline phosphatase with lumigen-paraphenylenediamine substrate (5). This method allows flexibility in probe sequence selection, independent of restriction enzyme site location, and it works well with small probes. This approach allows sensitive differential analysis of closely related members of a gene family.

Base Sequence↗
PubMed1994

Yeast squalene synthase. A mechanism for addition of substrates and activation by NADPH.

Squalene synthase catalyzes the condensation of two molecules of farnesyl diphosphate (FPP) to give presqualene diphosphate (PSPP) and the subsequent reductive rearrangement of PSPP to squalene. Previous studies of the mechanism of addition of FPP to the enzyme have led to conflicting interpretations of initial velocity measurements (Beytia, E., Qureshi, A. A., and Porter, J.W. (1973) J. Biol. Chem. 248, 1856-1867; Agnew, W.S., and Popjak, G. (1978) J. Biol. Chem. 253, 4566-4573). Initial velocities for synthesis of PSPP and squalene were measured over a wider range of FPP and NADPH concentrations than previously reported, using a soluble form of recombinant enzyme. In the absence of NADPH, PSPP formation was activated by FPP at concentrations above approximately 0.5 microM. At fixed levels of NADPH, the dependence of initial rates of PSPP and squalene synthesis on FPP concentrations indicated that the C15 substrate added by a sequential mechanism. In addition, NADPH stimulated synthesis of PSPP by 40-fold at saturating levels of the cofactor. This stimulation is, at least in part, by reduction of PSPP to squalene.

Enzyme Activation↗
PubMed1994

Polarity conserved positions in transmembrane domains of G-protein coupled receptors and bacteriorhodopsin.

The polarity of residues at certain positions in the transmembrane domains of G-protein coupled receptors (GPCR) is found to be conserved, and to indicate the pattern of specific helix-helix packing of the helices. A concept of polarity conserved positions (PCP) is proposed to describe this conserved property, and is applied to obtain insight into the structural features of the transmembrane proteins. The common pattern of PCPs for GPCRs indicates that they share a similar packing arrangement of their transmembrane helix bundles. For proteins in the bacteriorhodopsin family the PCP pattern suggests a common packing arrangement that differs from that of GPCRs, in agreement with experimental data. This difference in the packing arrangement underscores the shortcomings of a BR template for the construction of molecular models of GPCRs.

Amino Acid Sequence↗
PubMed1994

Effects of the seed sludge on the performance of UASB reactors for treatment of toxic wastewater.

A comparative study of different sludges (anaerobic sewage sludge and anaerobic sewage sludge cultivated for 30 days) as the seed of UASB reactors for treatment of synthetic resin production wastewater was carried out on a laboratory scale. Significant differences in reactor performance were observed. With anaerobic sewage sludge seed, the reactor obtained a 71% COD removal efficiency and produced 2.94 dm3 biogas per dm3 wastewater under an organic loading rate of 4.5 kg COD m-3 day-1. The sludge in the reactor was diffuse and possessed poor settling ability, which led to effluent SS as high as 1200 mg dm-3. However, with anaerobic sewage sludge cultivated with synthetic substrate for 30 days as a seed, the same reactor gave 78% COD removal efficiency and produced 3.5 dm-3 biogas per dm3 wastewater at the same loading rate. Moreover, the sludge in the reactor was completely granulated and possessed good settling ability, which resulted in effluent SS as low as 200 mg dm-3. The granular sludge produced less biomass per gram COD removed than the diffused sludge. Anaerobic sewage sludge cultivated for a short time could form the nuclei of granules for the reactor, allowing granulation to proceed smoothly. Therefore, sludge nuclei are a prerequisite of sludge granulation in UASB reactors for treatment of toxic wastewater.

Anaerobiosis↗
PubMed1994

Expression of trk and neurotrophin mRNA in dorsal root and sympathetic ganglia of the quail during development.

The nerve growth factor (NGF) family of neurotrophins exerts effects by binding to products of the trk family of proto-oncogenes. We examined the expression of both trk and neurotrophin mRNA during the entire range of development of quail dorsal root ganglia (DRG) and sympathetic ganglia (SG) using in situ hybridization and reverse transcriptase-polymerase chain reaction (RT-PCR). TrkC mRNA was present in neurons or their precursors from the time of formation of DRG (stage 18, embryonic day 2.5 [E2.5]) and throughout development. The number of labeled cells changed, however, from a majority to a minority at later developmental stages. Expression of trkA mRNA was not detected in DRG until stage 30 (E6) by in situ hybridization, although results with RT-PCR were positive at stage 23 (E3.5). Labeling was always detected on a majority of neurons or their precursors. SG exhibited low levels of trkC mRNA during the later stages of development, whereas trkA mRNA was present from stage 34 onward in most neurons. We have also shown that NGF, neurotrophin-3 (NT-3), and brain-derived neurotrophic factor (BDNF) mRNA were present at all stages examined (stages 23 through 45 for DRG, stages 35-36 and 45 for SG). In DRG, NGF mRNA expression was limited to support cells, whereas NT-3 and BDNF mRNA were detected in both neurons and support cells. These results suggest that neurotrophins could serve a local function in developing ganglia, which can be correlated with the presence of their respective receptors.

Animals↗
PubMed1994

The onset of neurotrophin and trk mRNA expression in early embryonic tissues of the quail.

To determine the role of neurotrophins on the initial development of the avian embryo, RT-PCR was used to detect when mRNA for nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3), as well as their respective receptors, trkA, trkB, and trkC, is first expressed in the avian embryo. trkA, BDNF, trkB, NT-3, and trkC mRNA were expressed as early as stage 1 ("prestreak" stage), while NGF mRNA was not expressed until later in development (stage 5, "notochord" stage). Microdissection of Embryonic Day 2 quail (stages 12 to 14) and RT-PCR analysis revealed that the neural crest, neural tube, somites, or notochord all expressed some neurotrophin or trk mRNA. Although a neurotrophin and its appropriate receptor were both often present or absent, in several cases they were present individually, suggesting that they might have either local or target-derived actions.

Animals↗
PubMed1994

Environmental and behavioral influences on plasma lipoprotein(a) concentration in women twins.

BACKGROUND: Genetic factors are firmly established as determinants of plasma lipoprotein(a) [Lp(a)] concentration. This study focused on behavioral or environmental factors that might also explain some of the variation in levels of this cardiovascular disease risk factor. METHODS: The study considers the 644 women twins (597 whites, 47 blacks; ages 30-91 years) who participated in the second examination of the Kaiser Permanente Women Twins Study. Cross-sectional associations of behaviors and environmental factors with Lp(a) concentration were studied before and after removing genetic influences on Lp(a) levels. RESULTS: Lp(a) levels were substantially higher among blacks than whites (P < 0.0001). The distribution of apo(a) size phenotypes also differed between blacks and whites, but this variation did not explain the difference in Lp(a) levels. A positive association of Lp(a) concentration with age was noted among blacks (P = 0.06) but not among whites (P = 0.86). No evidence was found for associations of Lp(a) with menopausal status, cigarette smoking, alcohol consumption, total or heavy recreational physical activity, 11-year weight gain, use of several antihypertensive medications, or diabetes status in either race. Among postmenopausal women, however, estrogen replacement therapy was associated with lower Lp(a) levels among whites (7.9 vs 9.9 mg/dl, P = 0.05). Removing genetic variation in Lp(a) concentration by matching 171 monozygotic (MZ) twins to their genetically identical co-twins did not alter these findings. CONCLUSION: The plasma concentration of Lp(a), unlike other lipoprotein risk factors for heart disease, has few behavioral or environmental correlates, at least among white women. Neither behavioral or environmental factors nor variation in the apo(a) size phenotype appeared to explain the higher mean Lp(a) levels among black compared with white women; further study seems warranted in larger samples of black women.

Adult↗
PubMed1994

Nucleotide sequence of an Onchocerca volvulus cDNA clone encoding an antigen homologous with the intermediate filament protein family.

A series of clones were isolated from an O. volvulus lambda gt11 cDNA library on the basis of strong recognition by sera from both Onchocerca volvulus or Wuchereria bancrofti patients. Several of these clones encoded a protein which clearly belonged to the intermediate filament (IF) class, and had most similarity with A1IF-A from Ascaris lumbricoides and a number of IF proteins from molluscs. Western blotting experiments implied that the first coiled domain appears to be markedly less antigenic in vivo than the remainder of the O. volvulus protein.

Amino Acid Sequence↗
PubMed1994

Specificity and structure of murine monoclonal antibodies against GM1 ganglioside.

Anti-GM1 antibodies have been implicated in the pathogenesis of several neurological diseases, but the role of these antibodies is still controversial. An animal model could provide insight into the mechanisms of these human disorders, but obtaining specific anti-GM1 monoclonal antibodies (mAbs) has been extremely difficult because of the weak immunogenicity of GM1 ganglioside. Four murine mAbs against GM1 were elicited by immunization of mice with lyso GM1 coupled to BSA and GM1 glycolipid. All four IgM,k mAbs bound strongly to GM1, three antibodies (125, 360 and 494) also bound very weakly to asialo GM1 (GA1) and one (156) bound weakly to GD1b. Three antibodies (125, 360 and 494) were encoded by the same VH and V kappa genes. The VH gene exhibited 97% homology to VHOX1, a member of the VHQ52N gene family, the D segment was probably derived from DQ52 and JH was identical to JH2. The V kappa gene was approximately 99% homologous to V kappa RF and J kappa was germline J kappa 2. The VH gene of mAb 156 exhibited 98% homology to VH205.12, of the VHJ558 gene family, the D segment was derived from DFL16.1, and JH was germline JH2. The V kappa and J kappa genes of mAb were identical to V kappa 8 and J kappa 1, respectively. The genes encoding these anti-GM1 antibodies were close to germline sequences and have been used to encode other antibodies. This suggests that the unresponsiveness of mice to immunization is probably due to inactivation of self-reactive B cells. These rare anti-GM1 mAbs will be valuable reagents for studies of the pathogenesis of autoimmune neuropathy in animals, and also for analyzing the tissue distribution and functions of GM1.

Amino Acid Sequence↗
PubMed1994

Identification and characterisation of a novel repetitive antigen from Onchocerca spp.

A novel repetitive antigen from the cattle parasite Onchocerca gibsoni was shown to be recognised by sera from humans infected with Onchocerca volvulus, Wuchereria bancroftii or Brugia malayi. The O. gibsoni protein was produced in a recombinant form, and antibodies raised to this protein used to screen cDNA libraries for O. volvulus. A series of clones were isolated which encoded repetitive regions very similar to those in O. gibsoni, but interspersed between these were longer repeating units which we have not so far found in O. gibsoni. The repetitive antigen was shown to be of high molecular weight and present only in the insoluble (membrane) fraction of O. gibsoni microfilariae. Immunofluorescence techniques demonstrated that the antigen was associated both with muscle and with specific membrane layers, including a peripheral layer which corresponds to either the outer hypodermis or an inner region of the cuticle in adult female O. gibsoni. In many respects, the proteins encoded by the O. gibsoni and O. volvulus cDNA clones resembled repetitive antigens from several distantly related eukaryotic parasites, and a possible common role in immune evasion is discussed.

Amino Acid Sequence↗
PubMed1994

Anatomical characterization of retinal ganglion cells that project to the nucleus of the basal optic root in the turtle (Pseudemys scripta elegans).

There is little detailed information about retinal ganglion cells which project to specific central targets in the brain. The present study examined retinal ganglion cells projecting to the nucleus of the basal optic root, a major accessory retinal target in the turtle. These ganglion cells were first selectively labeled using retrograde transport of rhodamine injected stereotaxically into the nucleus of the basal optic root. The number and distribution of the retrogradely labeled cells in the retina was then determined. Some of these retrogradely labeled cells were then injected intracellularly with Lucifer Yellow, photoconverted using diaminobenzidine, and drawn in detail using a camera lucida attachment. There were approximately 1500 ganglion cells in each retina which projected to the nucleus of the basal optic root, of which 20% had cell bodies displaced to the inner nuclear layer. More than 50% of the total population was concentrated in the visual streak region. All ganglion cells projecting to the nucleus of the basal optic root, both normal and displaced, had monostratified dendritic arborizations in stratum 1 of the inner plexiform layer. About 41% of these ganglion cells had elongated dendritic arborizations with distinct orientations, which may suggest a correlation of morphology and function. There were similarities in the overall appearance, and in the type and stratification of the dendritic arborizations of all ganglion cells projecting to the nucleus of the basal optic root. These anatomical similarities are consistent with the previously demonstrated similarities in physiology and may reflect a common role for these ganglion cells in visual processing.

Animals↗
PubMed1994

The potential role of nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 in avian cochlear and vestibular ganglia development.

The role of the nerve growth factor family of neurotrophins in the development of cochlear and vestibular ganglia is unclear. In order to predict the potential importance of nerve growth factor, brain-derived neurotrophic factor or neurotrophin-3, we examined the expression of neurotrophin mRNA and full-length neurotrophin receptor mRNA by in-situ hybridization and reverse transcription-polymerase chain reaction, as well as whether high affinity 125I-nerve growth factor binding was present, in cochlear and vestibular ganglia of the quail at several stages of development (stages 26, 31 and 36). Nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 mRNA was detected at all ages examined, suggesting that these neurotrophins may serve an autocrine or paracrine function, especially prior to target contact. In addition, we found full-length trkA and trkC mRNA was expressed, the products of which are the functional neuronal receptors for nerve growth factor and neurotrophin-3, respectively. Although full-length trkA mRNA was found, physiologically important high affinity 125I-nerve growth factor binding was not detected. Since nerve growth factor's effects on survival and neurite outgrowth are mediated through high affinity binding, nerve growth factor may serve an as yet unidentified role in this system. Full-length trkB mRNA, the product of which is the functional neuronal receptor for brain-derived neurotrophic factor, was not detected using reverse transcription-polymerase chain reaction, however, truncated (non-catalytic) trkB was present, at least in cochlear ganglia at stage 31. It is not known what function may be subserved by these truncated receptors.

Animals↗