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Biomedical subjects

D Zhang

Publications and source records attributed to D Zhang.

At least 523 records · Page 29Linked to original sources
PubMed1996

[Endoscopic surgery of the cerebellopontine angle].

Twenty-four patients with various cerebellopontine angle (CPA) disorders including hemifacial spasm (11 cases), trigeminal neuralgia (9 cases), glossopharyngeal neuralgia (2 cases) incapacitating vertigo and acoustic neuroma (one case each), were treated by endoscopic surgery, via the retrosigmoid approach. Because of the distal light and panoramic view, the endoscope provides an excellent view inside the CPA, allows clear identification of the vascular and nervous components, and is especially helpful in cases of trigeminal neuralgia and hemifacial spasm to find the location of cross-conflict. Under the monitor of endoscope, the surgeon is able to perform facial nerve decompression and splitting, selective trigeminal nerve root and glossopharyngeal nerve section with ease and safty. The present study shows that the endoscopic surgery is a simple and useful procedure which helps to reduce surgical complications. We recommend the application of endoscopy in the management of CPA disorders.

Adult↗
PubMed1996

A dynamic and quantitative study of pattern visual evoked potentials and gamma-aminobutyric acid neurones in the lateral geniculate nucleus and the visual cortex of monocular deprivation cats.

PURPOSE: To assess the effects of monocular lid closure during critical period on cortical activity. METHOD: Pattern visual evoked potentials (PVEP) of the normal and the monocular deprivation (MD) cats were dynamically measured and the number of gammaaminobutyric acid immunopositive (GABA-IP) neurones of the area 17 of the visual cortex and the lateral geniculate nucleus (LGN) was quantitatively compared by using immunohistochemical method (ABC). RESULTS: The amplitude of the N1-P1 attenuated in deprived eyes (DE), NE/DE at postnatal week (PNW) 7-8 (P < 0.05), NE/DE at PNW 15-16 (P < 0.01); while P1 latency delayed, NE/DE at PNW 7-8 (P > 0.05), NE/DE at PNW 15-16 (P< 0.05). The numbers of GABA-IP neurones in layer A1 of the ipsilateral LGN and in layer A of the contralateral LGN, compared to those in the corresponding normal laminae, were not significant at PNW 7-8 and PNW 11-12 (P > 0.05), while in the same cats a reduction in the number of GABA-IP neurones was found in layer IV of area 17 at PNW 11-12 (P < 0.05). However, with longer survival of 3-4 weeks in duration, the numbers of GABA-IP neurones in the deprived laminae of LGN were remarkably reduced (P < 0.05). CONCLUSIONS: The amplitude of N1-P1 components is sensitive to the effects of monocular deprivation. Monocular deprivation in cats during critical period leads to dramatic changes of the number of GABA-IP neurones in the LGN and cortical layer IV receiving inputs from the deprived eye in cats. The deprivation-induced reduction in GABA-IP neurones is delayed in the LGN compared with the visual cortex. PVEP of the MD cats is consistent with the damage of its GABA system in visual cortex.

Animals↗
PubMed1996

In vivo observations and electron microscopy of treatment of experimental HSV keratitis with anti-HSV monoclonal antibodies.

PURPOSE: To study the antiviral activity of monoclonal antibodies (McAb) in vivo and identify their effects on experimental herpetic keratitis. METHODS: Topical use of anti-HSV monoclonal glycoprotein antibodies was carried out on acute herpetic keratitis of rabbits infected by HSV-1 SM44. The application of the eye drops in each group was five times per day for 14 days by double-blind method. In vivo observation and electron microscopy were performed during the whole procedure. The anti-HSV McAb's solution was mixed up of five monoclonal antibodies with high neutrilization titers and/or high ADCC activity. RESULTS: Compared with placebo-treated eyes, anti-HSV McAb treatment made statistically significant reduction of herpetic corneal epithelial lesion on rabbits from day 3 to day 14 postinnoculation (P < 0.01). Punctate and short dendritic lesion were the main patterns. The area of involvement was also limited. Electron microscopic analysis showed ultrastructural changes of herpetic corneal infection. The clumping of nuclear chromatin, swollon nuclei, reduction of microflament, rounding of epithelial cells were apparent in placebo-treated eyes. The advanced lesion of the viral infection was karyolysis, karyoklasis and disruption of cells in both scanning and transmission electron micrographes. The management of the McAb-treated eyes showed that the pathological involvements as mentioned above reduced remarkably. CONCLUSION: Topical application of anti-HSV monoclonal antibodies produced marked antiviral effects in inhibiting the development of experimental herpetic keratitis in rabbits and in protecting the susceptible corneal cells. As a new biological product, the anti-HSV monoclonal antibodies may provide a new approach to the treatment of HSV keratits.

Animals↗
PubMed1996

[Surgical treatment for congenital motive defect nystagmus by the parks (5, 6, 7, 8mm) procedure or the augmented Parks procedure].

PURPOSE: The purpose of the surgical treatment for patients with congenital motive detect nystagmus was to correct deviation of the eye and the head tilt, to improve vision and eliminate nystagmus. METHODS: 19 patients underwent the Parks (5, 6, 7, 8mm) or the augmented Parks procedure from 1987 to 1994. For patients with abnormal head turn > or = 30 degrees, We used a 40-60% augmented Parks procedure. RESULTS: A follow up of 19 patients ofr an average of 22 months revealed a marked improvemtnts. After operation, the head turn was decreased form 30.5 degrees to 4.9 degrees, the intensity of nystagmus was decreased from 36.0 to 9.7, 21 eyes (55.3%) of 19 patients improved by two or more lines of Snellen visual acuity. CONCLUSIONS: The Parks (5, 6, 7, 8mm) and the augmented Parks (5, 6, 7, 8mm) procedure produce a marked correction for congenital motive defect nystagmus.

Adolescent↗
PubMed1995

Cloning of a gamma-aminobutyric acid type C receptor subunit in rat retina with a methionine residue critical for picrotoxinin channel block.

Ionotropic receptors for gamma-aminobutyric acid (GABA) are important to inhibitory neurotransmission in the mammalian retina, mediating GABAA and GABAC responses. In many species, these responses are blocked by the convulsant picrotoxinin (PTX), although the mechanism of block is not fully understood. In contrast, GABAC responses in the rat retina are extremely resistant to PTX. We hypothesized that this difference could be explained by molecular characterization of the receptors underlying the GABAC response. Here we report the cloning of two rat GABA receptor subunits, designated r rho 1 and r rho 2 after their previously identified human homologues. When coexpressed in Xenopus oocytes, r rho 1/r rho 2 heteromeric receptors mimicked PTX-resistant GABAC responses of the rat retina. PTX resistance is apparently conferred in native heteromeric receptors by r rho 2 subunits since homomeric r rho 1 receptors were sensitive to PTX; r rho 2 subunits alone were unable to form functional homomeric receptors. Site-directed mutagenesis confirmed that a single amino acid residue in the second membrane-spanning region (a methionine in r rho 2 in place of a threonine in r rho 1) is the predominant determinant of PTX resistance in the rat receptor. This study reveals not only the molecular mechanism underlying PTX blockade of GABA receptors but also the heteromeric nature of native receptors in the rat retina that underlie the PTX-resistant GABAC response.

Amino Acid Sequence↗
PubMed1995

The effect of interleukin-1 on C-reactive protein expression in Hep3B cells is exerted at the transcriptional level.

The combination of interleukin 6 (IL-6) and interleukin 1 (IL-1) synergistically induces the human acute-phase reactant, C-reactive protein (CRP) in Hep3B cells. While previous studies have indicated that IL-6 induces transcription of CRP, the mode of action of IL-1 has not been clearly defined. It has been suggested that the effect of IL-1 might be post-transcriptional, exerted through the 5'-untranslated region (5'-UTR). To evaluate the role of IL-1 in CRP gene expression, we studied the effects of interleukin-6 (IL-6) and interleukin-1 beta (IL-1 beta) on both the endogenous CRP gene and on transfected CRP-CAT constructs in Hep3B cells. In kinetic studies of the endogenous CRP gene, IL-1 beta alone had no effect on CRP mRNA levels, but when added to IL-6, synergistically enhanced both CRP mRNA levels and transcription, as determined by Northern-blot analyses and nuclear run-on studies. IL-6 alone and the combination of [IL-1 beta + IL-6] each induced increases in mRNA levels roughly comparable with observed increases in transcription. These findings indicate that the effect of IL-1 beta on CRP expression is exerted largely at the transcriptional level in this system. This conclusion was confirmed by studies in Hep3B cells transiently transfected with CRP-CAT constructs, each containing 157 bp of the CRP 5'-flanking region but differing in the length of the 5'-UTR from 104 bp to 3 bp. All constructs responded in the same way; IL-6, but not IL-1 beta, induced significant chloramphenicol acetyltransferase (CAT) expression which was synergistically enhanced 2- to 3-fold by IL-1 beta. These results indicate that IL-1 beta stimulates transcriptional events in the presence of IL-6 and that the upstream 157 bases of the CRP promoter contain elements capable of both IL-6 induction and the synergistic effect of IL-1 beta on transcription.

C-Reactive Protein↗
PubMed1995

Chimeric zeta-receptors direct human natural killer (NK) effector function to permit killing of NK-resistant tumor cells and HIV-infected T lymphocytes.

Chimeric receptors in which a signaling component of the TCR complex such as zeta is fused directly to the ligand binding domain of a heterologous receptor or Ab have been shown to redirect the specific effector activity of T lymphocytes. We previously described the ability of two classes of such chimeric zeta-receptors bearing extracellular domains derived from either the HIV receptor CD4 (CD4 zeta) or an HIV-specific single chain Ab to redirect primary human CD8+ T cells to kill HIV-infected T cells. In this report we demonstrate that human NK cells can be genetically modified to express high levels of CD4 zeta using retroviral transduction. The CD4 zeta chimeric receptor is biochemically active, as cross-linking of CD4 zeta on NK cells results in tyrosine phosphorylation of CD4 zeta and multiple cellular proteins. More importantly, the CD4 zeta chimeric receptor is functionally active and can direct NK cells to specifically and efficiently lyse either NK-resistant tumor cells expressing the relevant ligand, gp120, or CD4+ T cells infected with HIV. These results show that human NK cells can be readily activated via zeta-based chimeric receptors to target both tumor and virally infected cells, and suggest a novel approach to the treatment of disease.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1995

Related contribution of specific helix 2 and 7 residues to conformational activation of the serotonin 5-HT2A receptor.

A conserved helix 2 Asp is required for the proper function of many G-protein-coupled receptors. To reveal the structural basis for the role of this residue, the additive effects of mutations at this locus and at a conserved helix 7 locus were investigated in the 5-HT2A receptor. All mutant receptors studied retained high affinity agonist and antagonist binding. Whereas an Asp-->Asn mutation in helix 2 eliminated coupling, interchanging the residues at the two positions by a second mutation of Asn-->Asp in helix 7 restored receptor function. These data suggest that these residues are adjacent in space and interact. The loss of function observed with Ala at either position is consistent with each side chain forming hydrogen bonds. Molecular dynamics simulations were performed on three-dimensional computational models of agonist-receptor complexes of both the wild-type receptor and the Asp-->Asn mutant receptor. Consonant with the lack of coupling observed for the mutant construct, introducing the mutation into the computational model produced a conformational change in a direction opposite to that seen from computational simulations of activation of the wild-type receptor model. These results implicate both loci in a common hydrogen-bonding network underlying receptor activation by agonist.

Mutation↗
PubMed1995

Transcriptional or translational inhibition blocks low dose NMDA-mediated cell death.

Glutamate toxicity in nerve cells has been well documented and may play a role in a broad spectrum of neurological and ophthalmic diseases. Recent work in several laboratories has suggested that an apoptotic-like mechanism may be implicated in glutamate toxicity under certain circumstances. We therefore studied the effects of transcriptional and translational inhibition on glutamate-mediated cell death in retinal ganglion cells. We now report that either cycloheximide or actinomycin D can, even when added 2 h after the initial excitotoxic insult, save retinal ganglion cells from low dose glutamate toxicity. However, cycloheximide or actinomycin D are unable to prevent glutamate-mediated death at higher concentrations of excitotoxin. This result indicates that at low doses, the neurotoxic effects of glutamate may develop through an apoptotic-like mechanism.

Animals↗
PubMed1995

Isolation and characterization of mosquito ferritin and cloning of a cDNA that encodes one subunit.

Ferritin, an iron storage protein, was isolated from larvae and pupae of Aedes aegypti grown in an iron-rich medium. Mosquito ferritin is a high molecular weight protein composed of several different, relatively small, subunits. Subunits of molecular mass 24, 26, and 28 kDa are equally abundant, while that of 30 kDa is present only in small amounts. The N-terminal sequence of the 24 and 26 kDa subunits are identical for the first 30 amino acids, while that of the 28 kDa subunit differs. Studies using antiserum raised against a subunit mixture showed that the ferritin subunit were present in larvae, pupae, and adult females, and were increased in animals exposed to excess iron. The antiserum also was used to screen a cDNA library from unfed adult female mosquitoes. Nine clones were obtained that differed only in a 27 bp insertion in the 3' end. Rapid amplification of cDNA ends (RACE) was used to obtain the complete protein coding sequence. A putative iron-responsive element (IRE) is present in the 5'-untranslated region. The deduced amino acid sequence shows a typical leader sequence, consistent with the fact that most insect ferritins are secreted, rather than cytoplasmic proteins. The sequence encodes a mature polypeptide of 20,566 molecular weight, smaller than the estimated size of any of the subunits. However, the sequence exactly matches the N-terminal sequences of the 24 and 26 kDa subunits as determined by Edman degradation. Of the known ferritin sequences, that of the mosquito is most similar to that of somatic cells of a snail.

Aedes↗
PubMed1995

Medical knowledge systems: applications to telemedicine.

The application and form of electronically stored medical knowledge has a direct impact on the design of any healthcare delivery system. For those who plan for remote medical care or who work at the disaster relief level, there are specific requirements which will dictate the type of knowledge required and the vehicle best suited to deliver that information. The PC based multimedia biomedical library developed for NASA was originally intended for long-term space missions where complete isolation from each support was a distinct possibility. The library is a combination of traditional references and secondary databases structured within a primary care physician's workstation. The integration of the library and a point-of-care system allows optimal use of both resources and provides a basic building block for telemedicine networking.

Artificial Intelligence↗
PubMed1995

Characterization of a novel non-muscle myosin-related protein from Onchocerca gibsoni.

A cDNA library was constructed in lambda gt11 using poly(A)+ mRNA from early larvae of Onchocerca gibsoni. Screening of the library using serum from a single onchocerciasis patient yielded several strongly immunoreactive clones, one of which (OGK2) was found to encode a novel myosin-related protein. cDNA clone OGK2 contained an insert of 2017 bp, consisting of continuous open reading frame in frame with the vector, hence this clone encodes 671 amino acid residues of a larger protein. A fragment (619 nt) of the OGK2 cDNA was subcloned into the expression vector pGEX-1N to generate a glutathione S-transferase fusion protein. Polyclonal antiserum raised to this fusion protein strongly recognised an O. gibsoni protein of approximately 220 kDa. Immunolocalization studies indicated that this protein was associated predominantly with the hypodermis and a number of other specific membrane layers in the adult parasite. Myosin-related proteins are frequently immunodominant parasite antigens and in a number of studies have been shown to confer a degree of protective immunity against the corresponding parasite. Evaluation of the protective potential of the OGK2 protein, therefore, appears to be warranted.

Amino Acid Sequence↗
PubMed1995

Class I MHC alpha 3 domain can function as an independent structural unit to bind CD8 alpha.

Functional interactions between CD8-dependent cytotoxic T cells and their targets require physical contact between CD8 and a non-polymorphic determinant on the alpha 3 domain of the class I MHC molecule. We developed a cell-free assay to directly monitor this molecular interaction, specifically excluding the participation of other cellular proteins and lipids. This assay employed a soluble CD8 derivative and a plate-bound HLA-A2.1 derivative, alpha 3/MalE, in which the alpha 3 domain has been expressed independently of its neighboring polypeptide domains on the native class I MHC molecule and beta 2-microglobulin (beta 2-m). These proteins were produced using eukaryotic and prokaryotic expression systems, respectively. Our data demonstrated specific, saturable binding between soluble CD8 alpha (sCD8 alpha) and alpha 3/MalE, and the Kd of this interaction was determined to be 4.5 x 10(-7) M. Monoclonal antibodies (mAb) directed against either CD8 or the alpha 3 domain of class I MHC inhibited binding; mAb directed against other sites on class I MHC and beta 2-m did not. Our data suggest that the interaction between CD8 alpha and the alpha 3 domain of class I MHC does not require the participation of neighboring class I sequences or beta 2-m.

Base Sequence↗
PubMed1995

Co-expression of AMPA/kainate receptor-operated channels with high and low Ca2+ permeability in single rat retinal ganglion cells.

The patch-clamp technique was used to record whole-cell currents induced by alpha-amino-3-hydroxyl-5-methyl-isoxazol-4-propionic acid (AMPA) or kainate in solitary rat retinal ganglion cells (n = 125) in vitro. Two groups of retinal ganglion cells could be distinguished according to their responses to kainate or AMPA in extracellular solutions with Ca2+ as the only permeant cation. The ratio of the steady-state currents evoked by a given concentration of AMPA compared to kainate was low (0.08) in the first group and high (0.61) in the second group of retinal ganglion cells. The Ca2+ permeability through AMPA/kainate receptor-operated channels was low (PCa2+/PCs+ < 0.1) in the first group (n = 74, 59%) and moderate (PCa2+/PCs+ = 0.53) in the second group (n = 51, 41%) of retinal ganglion cells. The fraction of the total current induced by stimulation of non-N-methyl-D-aspartate receptors that is flowing through Ca2+ permeable AMPA/kainate channels in single cells with high Ca2+ permeability was estimated by comparing the current-voltage relationship in extracellular solutions with either Ca2+ or Na+ as the sole charge carrier. The contribution of Ca(2+)-permeable channels to the non-N-methyl-D-aspartate receptor induced whole-cell current in single Ca2+ permeable cells (n = 12) ranged from 40 to 70%, correlating with the intermediate level of Ca2+ permeability (PCa2+/PCs+ = 0.22-0.80) measured by an independent method in these cells. Thus, single Ca(2+)-permeable cells appear to express at least two types of AMPA/kainate receptor-operated channels with high or low Ca2+ permeability. Using the polymerase chain reaction, transcripts for the glutamate receptor subunits 1-4, including their "flip" and "flop" versions, were identified in retinal ganglion cells. Together, these findings suggest that among rat retinal ganglion cells there are differences in the pattern of expression of AMPA/kainate receptor-operated channels. Moreover, individual cells co-express multiple heterologous non-N-methyl-D-aspartate receptors with distinct functional properties. The functional diversity of these receptors may play an important role in controlling Ca2+ entry into neurons. We speculate that the low Ca2+ permeability and the preference for kainate in one group of retinal ganglion cells may be due to the predominant expression of non-N-methyl-D-aspartate receptors containing the edited form of the glutamate receptor subunit 2 flop splice variant.

Animals↗
PubMed1995

A possible mechanism of the specific action of bisphosphonates on osteoclasts: tiludronate preferentially affects polarized osteoclasts having ruffled borders.

The mechanism of action of tiludronate [(4-chlorophenyl)-thiomethylene bisphosphonate] on osteoclastic bone resorption was examined in mouse culture systems. Tiludronate did not inhibit the formation of osteoclast-like multinucleated cells (OCLs) induced by 1 alpha,25-dihydroxyvitamin D3 in cocultures of mouse osteoblastic cells and bone marrow cells. OCLs obtained from cocultures on collagen gel-coated dishes, treated with tiludronate, formed as many resorption pits on dentine slices as those obtained from the control cocultures. However, pit formation by OCLs was dose-dependently inhibited when tiludronate was added directly to the pit formation assay. Other bisphosphonates such as alendronate and etidronate dose-dependently inhibited pit formation according to the in vivo potencies of the respective bisphosphonates to inhibit bone resorption. However, they had no inhibitory effect on the recruitment of OCLs induced by 1 alpha,25-dihydroxyvitamin D3 in the cocultures. When OCLs were placed on dentine slices, they formed the ringed structure of F-actin-containing podosomes and ruffled borders (polarized OCLs) even in the presence of tiludronate. However, the actin rings in OCLs were disrupted by the addition of tiludronate soon after they began to resorb dentine. In contrast, OCLs placed on collagen gel formed neither actin rings nor ruffled borders (nonpolarized OCLs), and showed no response to tiludronate. OCLs formed from the spleen cells of osteosclerotic (oc/oc) mice developed the ringed structure of podosomes, but not ruffled borders, on dentine slices. The actin ring in the oc/oc spleen cell-derived OCLs placed on dentine slices was not disrupted by the addition of tiludronate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

The impact of chromosomes and centrosomes on spindle assembly as observed in living cells.

We analyzed the role that chromosomes, kinetochores, and centrosomes play in spindle assembly in living grasshopper spermatocytes by reconstructing spindles lacking certain components. We used video-enhanced, polarization microscopy to distinguish the effect of each component on spindle microtubule dynamics and we discovered that both chromosomes and centrosomes make potent and very different contributions to the organization of the spindle. Remarkably, the position of a single chromosome can markedly affect the distribution of microtubules within a spindle or even alter the fate of spindle assembly. In an experimentally constructed spindle having only one chromosome, moving the chromosome to one of the two poles induces a dramatic assembly of microtubules at the nearer pole and a concomitant disassembly at the farther pole. So long as a spindle carries a single chromosome it will persist normally. A spindle will also persist even when all chromosomes are detached and then removed from the cell. If, however, a single chromosome remains in the cell but is detached from the spindle and kept in the cytoplasm, the spindle disassembles. One might expect the effect of chromosomes on spindle assembly to relate to a property of a specific site on each chromosome, perhaps the kinetochore. We have ruled out that possibility by showing that it is the size of chromosomes rather than the number of kinetochores that matters. Although chromosomes affect spindle assembly, they cannot organize a spindle in the absence of centrosomes. In contrast, centrosomes can organize a functional bipolar spindle in the absence of chromosomes. If both centrosomes and chromosomes are removed from the cell, the spindle quickly disappears.

Animals↗