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Biomedical subjects

M Yu

Publications and source records attributed to M Yu.

At least 199 records · Page 11Linked to original sources
PubMed1998

[A randomized control clinical trial of glaucoma filtering surgery with homoharringtonine].

OBJECTIVE: To study the antiproliferative effects of homoharringtonine (Hh) on glaucoma filtering surgery. METHODS: In a randomized control clinical trial, 78 patients (88 eyes) with refractory glaucoma underwent trabeculectomy with and without Hh. In the Hh-treated eyes (n = 46), the therapeutic dose of Hh was: intraoperative application of Hh 0.4 mg and postoperative subconjunctival injections of Hh 0.62 +/- 0.20 mg (ranged 0.53 - 0.75 mg). In the control eyes (n = 42), Hh was not used. The follow-up period was 18 to 48 months, and the data were analyzed by using the life-table method of Kaplan-Meier. RESULTS: The cumulative success probability in Hh group was 84.5% and that in control group was 50.9%, the difference being significant (P < 0.05). The cumulative percentage of functioning bleb in Hh group was 84.2% and that in control group was 52.9% (P < 0.05). The rates of corneal erosion were 23.9% and 7.1%, and the rates of conjunctival wound leak were 6.5% and 2.4% in Hh and control group respectively. There was no significant change in corneal endothelial density following the use of Hh (P > 0.05). CONCLUSION: The study indicates that Hh is a safe and effective antiproliferative agent for the use in glaucoma filtering surgery, it not only can increase the success probability considerably, but also maintain at least the postoperative IOP at relatively low normal level for 3 years.

Adult↗
PubMed1998

[Analysis of oscillatory potentials of flectroretinogram].

This study presents a method for the analysis of oscillatory potentials (OPs) of electroretinogram (ERG) in frequency domain and time domain. OPs from 9 cases (9 eyes) of branch retinal vein occlusion, 9 cases (9 eyes) of central retinal vein occlusion and 40 normal control eyes were tested. The frequency spectra of the OPs were derived through Fast Fourier Transform. The mean frequency spectra, the total power, the maximum magnitude, the maximum power and the dominant frequency in frequency domain of the OPs were calculated. The OPs waveforms were re-constructed with the OPs frequency spectra data by counter-Fast Fourier Transform. In time domain, the latencies, the amplitudes and the sum of the amplitudes of the four peaks of OPs were measured.

Electrophysiology↗
PubMed1998

[A study of affinity adsorbent AA-3 in cleaning the cycle immune complex of rabbits].

Conducted a hemoperfusion (HP) experiment on AA-3 for the treatment of type III allergy in rabbits and observed the change of Cycle Immune Complex (CLC) and the blood mutual adaptation (BMA). The results showed that the CIC level was 195.52 +/- 12.79 ug/ml before adsorption and 119.01 +/- 10.4 micrograms/ml after ansorption, the adsorption rate being (39.13 +/- 2.19)%. The experiment also demonstrated satisfactory BMA during AA-3 HP.

Adsorption↗
PubMed1998

Analysis of oscillatory potentials of flash electroretinogram in frequency domain and time domain in retinal vein occlusion.

PURPOSE: To analyse the parameters of frequency domain and time domain of the OPs in branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO). METHODS: OPs from 9 eyes of BRVO, 9 eyes of CRVO and 40 normal control eyes were tested. The frequency spectra of the OPs were derived through Fast Fourier Transform (FFT). The mean frequency spectra, the total power, the maximum magnitude, the maximum power and the dominant frequency in frequency domain of the OPs from the eyes of BRVO, CRVO and the normal control group were compared with each other. The OPs waveforms were reconstructed with the OPs frequency spectra data by counter-FFT. In time domain, the latencies, the amplitudes and the sum of the amplitudes of the four wavelets of OPs were measured and compared in the above subjects. RESULTS: There were no statistically significant differences in the magnitudes of frequency spectra, the total power, the maximum magnitude and the maximum power in the frequency range from 110 to 250 Hz between BRVO and normal subjects. However, in BRVO, the dominant frequency decreased significantly, the latencies of the first to the third OPs wavelet prolonged significantly, the amplitudes of the first and the second OPs wavelet and the summed amplitude of the four OPs wavelets attenuated significantly. Comparing the results of CRVO with those of normal subjects, there were statistically significant decrease in the magnitudes of frequency spectra from 150 to 180 Hz, there were statistically significant decrease in the total power, the maximum magnitude, the maximum power and the dominant frequency in the frequency range from 110 to 250 Hz, the latencies of the first to the fourth OPs wavelet prolonged significantly, the amplitudes of the first to the third OPs wavelet and the summed amplitude of the four OPs wavelets attenuated significantly. CONCLUSION: Some parameters of OPs in frequency domain and time domain are abnormal in branch retinal vein occlusion and in central retinal vein occlusion, which is more marked in the latter.

Aged↗
PubMed1998

Investigation of multifocal visual evoked potential in anisometropic and esotropic amblyopes.

PURPOSE: To investigate the variation of visual evoked potential (VEP) function at different eccentricities of the visual field in esotropic amblyopes and anisometropic amblyopes. METHODS: Data from 5 esotropic amblyopic eyes, 6 anisometropic amblyopic eyes, and 45 control eyes were analyzed. A VERIS system was used to generate a stimulus matrix containing 61 hexagons on a computer monitor. Each hexagon of the display contained a number of small black and white hexagonal patches that reversed in polarity during stimulation according to a pseudorandom binary m-sequence. The VERIS system extracted the local responses by cross-correlating the input and output signals. The latencies and amplitudes of the responses from the central 8.6 degrees of arc in the visual field were analyzed. RESULTS: In esotropic amblyopia, the multifocal VEP latency is prolonged, and the amplitude is reduced in the central region of the visual field. The mean amplitude is significantly smaller, and the mean latency is significantly longer in the temporal visual field than in the nasal visual field. In anisometropic amblyopia, latencies are markedly prolonged, and the amplitudes of multifocal VEP are attenuated in the central region of the visual field, and these effects are lessened in the periphery. CONCLUSIONS: The results are in agreement with psychophysical studies reporting a greater foveal deficit in amblyopia and a greater visual loss in the temporal field than in the nasal field in esotropic amblyopia.

Adolescent↗
PubMed1997

Carbonated apatite cement augmentation of pedicle screw fixation in the lumbar spine.

STUDY DESIGN: Biomechanical testing with human cadaveric lumbar vertebral bodies was used to determine the utility of an injectable carbonated apatite cancellous bone cement for improving the structural performance of pedicle screws subjected to axial pull-out or transverse cyclic loading. OBJECTIVES: To ascertain whether augmentation with a carbonated apatite cement can enhance pedicle screw fixation in the lumbar spine. SUMMARY OF BACKGROUND DATA: The beneficial effects of polymethylmethacrylate augmentation on pedicle screw pull-out strength have been demonstrated. Cancellous bone cement, however, may provide an attractive alternative in this application, as it is remodelable, biocompatible, and nonexothermic. METHODS: Forty-three cadaveric lumbar vertebral bodies were instrumented with pedicle screws. In 20 of these specimens, axial pull-out strength was compared between the control screws and those augmented with cancellous bone cement. In the remaining 23 specimens, the screws were loaded in the superior-inferior direction with a peak displacement of +/- 1 mm at a frequency of 3 Hz for 5000 cycles. Three parameters were calculated from the force-versus-time data: 1) the energy dissipated, 2) the peak force at the start of the test, and 3) the peak force at the end of 5000 cycles. RESULTS: The pull-out strength of the augmented pedicles averaged 68% greater than that of the control side. In response to cyclic loading, all measures of bio-mechanical performance improved 30-63%. CONCLUSIONS: The data suggest that augmentation with this carbonated apatite cancellous bone cement can enhance immediate screw fixation.

Adult↗
PubMed1997

Tyrosine phosphorylation mediates ConA-induced membrane type 1-matrix metalloproteinase expression and matrix metalloproteinase-2 activation in MDA-MB-231 human breast carcinoma cells.

ConA-induced cell surface activation of pro-matrix metalloproteinase-2 (pro-MMP-2) by MDA-MB-231 human breast cancer cells is apparently mediated by up-regulation of membrane type 1 MMP (MT1-MMP) through transcriptional and posttranscriptional mechanisms. Here, we have explored the respective roles of cell surface clustering and protein tyrosine phosphorylation in the ConA-induction effects. Treatment with succinyl-ConA, a variant lacking significant clusterability, partially stimulated MT1-MMP mRNA and protein levels but did not induce MMP-2 activation, suggesting that clustering contributes to the transcriptional regulation by ConA but appears to be critical for the nontranscriptional component. We further found that genistein, an inhibitor of tyrosine phosphorylation, blocked ConA-induced pro-MMP-2 activation and ConA-induced MT1-MMP mRNA level in a dose-dependent manner, implicating tyrosine phosphorylation in the transcriptional aspect. This was confirmed by the dose-dependent promotion of pro-MMP-2 activation by sodium orthovanadate in the presence of suboptimal concentrations of ConA (7.5 microg/ml), with optimal effects seen at 25 microg/ml orthovanadate. Genistein did not inhibit the ConA potentiation of MMP-2 activation in MCF-7 cells, in which transfected MT1-MMP is driven by a heterologous promoter, supporting the major implication of phosphotyrosine in the transcriptional component of ConA regulation. These data describe a major signaling event upstream of MT1-MMP induction by ConA and set the stage for further analysis of the nontranscriptional component.

Concanavalin A↗
PubMed1997

GA-binding protein-dependent transcription initiator elements. Effect of helical spacing between polyomavirus enhancer a factor 3(PEA3)/Ets-binding sites on initiator activity.

Many eukaryotic RNA polymerase II promoters contain initiator elements which direct accurate transcription in a TATA-independent manner. The PEA3/Ets-binding site (PEA3/EBS) is a common enhancer element in eukaryotic genes and is also found near the transcriptional start sites of many TATA-less promoters. We demonstrate that two PEA3/EBSs driving expression of the luciferase reporter gene, function as a minimal transcriptional initiator element. Maximal levels of transcription was achieved when two PEA3/EBSs, in either orientation, were located on the same face of the DNA helix, and the sites could be separated by up to three helical turns. In vitro transcription start sites directed by PEA3/EBS elements were clustered on either side of the upstream PEA3/EBS and were abolished by immunodepletion of GA-binding protein (GABP) from FM3A cell nuclear extracts. In vivo, co-transfection of GABPalpha and GABPbeta expression vectors enhanced reporter gene expression driven from PEA3/EBS initiator elements. Like other initiator elements, the PEA3/EBS elements were activated synergistically by upstream Sp1-binding sites. Thus, our results establish GABP as both a transcriptional activator factor and as an initiator factor.

3T3 Cells↗
PubMed1997

AAC-11, a novel cDNA that inhibits apoptosis after growth factor withdrawal.

Many growth factors and cytokines act as cellular survival factors by preventing programmed cell death (apoptosis). However, the specific genes and corresponding proteins that mediate survival are poorly defined. To identify potential survival genes, a cDNA library was prepared from murine fibroblasts and screened by a functional expression cloning approach. A 1023-bp cDNA, AAC-11, was identified that encodes a protein of approximately 25 kDa. The AAC-11 gene shows strong species conservation and is ubiquitously expressed in embryonic and adult tissues with multiple transcripts, as well as in various human tumor cell lines. The predicted protein contains a leucine zipper domain but lacks a DNA-binding domain. BALB/c3T3 fibroblasts that were stably transfected with AAC-11 cDNA were viable in serum-free medium for up to 12 weeks. The protective action of AAC-11 was abolished by mutation of leucines to arginines within the leucine zipper domain. We also isolated a longer AAC-11 cDNA that codes for up to an additional 290 amino-terminal amino acids but did not protect against apoptosis. The cDNA for human AAC-11 was identified and exhibits strong homology with the murine species and retains the leucine zipper domain. Western immunoblots of BALB/c3T3 cells using rabbit anti-AAC-11 polyclonal serum revealed a major native 55-kDa AAC-11 protein and a minor 25-kDa protein corresponding to the long and short forms of AAC-11 cDNA, respectively. In summary, we report a cDNA whose expression supports cell viability after withdrawal of growth factors. The corresponding native protein may function as a novel inhibitor of apoptosis.

Alternative Splicing↗
PubMed1997

Synthesis of prostaglandin E2 ethanolamide from anandamide by cyclooxygenase-2.

Because of its structural similarity to polyunsaturated fatty acids, anandamide could serve as substrate for enzymes such as lipoxygenases and cyclooxygenases, which metabolize polyunsaturated fatty acids to potent bioactive metabolites. Here the ability of recombinant human cyclooxygenase-1 (hCOX-1) and cyclooxygenase-2 (hCOX-2) to metabolize anandamide was studied. Baculovirus-expressed and -purified hCOX-2, but not hCOX-1, effectively oxygenated anandamide. Reverse phase high pressure liquid chromatography analysis of the products derived from 1-14C-labeled anandamide showed that the products formed are similar to those formed with arachidonic acid as substrate. The major prostanoid product derived from anandamide was determined by mass spectrometry to be prostaglandin E2 ethanolamide. Incubation of anandamide with lysates and the intact cell line expressing COX-2 but not that of COX-1 produced prostaglandin E2 ethanolamide. These results demonstrate the existence of a COX-2-mediated pathway for anandamide metabolism, and the metabolites formed represent a novel class of prostaglandins.

Amides↗
PubMed1997

Calcium influx inhibits MT1-MMP processing and blocks MMP-2 activation.

We have previously reported that concanavalin A (ConA)-induced MMP-2 activation involves both transcriptional and non-transcriptional mechanisms. Here we examined the effects of calcium influx on MT1-MMP expression and MMP-2 activation in MDA-MB-231 cells. The calcium ionophore ionomycin caused a dose-dependent inhibition of ConA-induced MMP-2 activation, but had no effect on MT1-MMP mRNA levels. However, Western analysis revealed an accumulation of pro-MT1-MMP (63 kDa), indicating that ionomycin blocked the conversion of pro-MT1-MMP protein to the active 60 kDa form. This suggests that increased calcium levels inhibit the processing of MT1-MMP. This finding may help to elucidate the mechanism(s) which regulates MT1-MMP activation.

Blotting, Northern↗
PubMed1997

Cloning of a gene (RIG-G) associated with retinoic acid-induced differentiation of acute promyelocytic leukemia cells and representing a new member of a family of interferon-stimulated genes.

In a cell line (NB4) derived from a patient with acute promyelocytic leukemia, all-trans-retinoic acid (ATRA) and interferon (IFN) induce the expression of a novel gene we call RIG-G (for retinoic acid-induced gene G). This gene codes for a 58-kDa protein containing 490 amino acids with several potential sites for post-translational modification. In untreated NB4 cells, the expression of RIG-G is undetectable. ATRA treatment induces the transcriptional expression of RIG-G relatively late (12-24 hr) in a protein synthesis-dependent manner, whereas IFN-alpha induces its expression early (30 min to 3 hr). Database search has revealed a high-level homology between RIG-G and several IFN-stimulated genes in human (ISG54K, ISG56K, and IFN-inducible and retinoic acid-inducible 58K gene) and some other species, defining a well conserved gene family. The gene is composed of two exons and has been mapped by fluorescence in situ hybridization to chromosome 10q24, where two other human IFN-stimulated gene members are localized. A synergistic induction of RIG-G expression in NB4 cells by combined treatment with ATRA and IFNs suggests that a collaboration exists between their respective signaling pathways.

Amino Acid Sequence↗
PubMed1997

Treatment of experimental autoimmune encephalomyelitis with genetically modified memory T cells.

The migratory properties of memory T cells provide a model vector system for site-specific delivery of therapeutic transgene factors to autoimmune inflammatory lesions. Lymph node cells from (SWRxSJL)F1 mice immunized with the p139-151 determinant of myelin proteolipid protein (PLP) were transfected with a DNA construct that placed the anti-inflammatory cytokine interleukin-10 (IL-10) cDNA under control of an antigen-inducible IL-2 promoter region. Isolated T cell clones demonstrated antigen-inducible expression of transgene IL-10 and expressed cell surface markers consistent with the phenotype of normal memory T cells. Upon adoptive transfer, transfected T cell clones were able to inhibit onset of experimental autoimmune encephalomyelitis (EAE) and to treat EAE animals therapeutically after onset of neurologic signs. Semiquantitative immunocytochemistry showed a significant correlation between decreased demyelination and treatment with the transfected T cells. Taken together, these data indicate the autoreactive T cells can be genetically designed to produce therapeutic factors in an antigen-inducible manner resulting in a decreased severity of clinical and histological autoimmune demyelinating disease.

Animals↗
PubMed1997

Normal and reactive NG2+ glial cells are distinct from resting and activated microglia.

We have previously used antibodies to the NG2 proteoglycan and the alpha receptor for platelet-derived growth factor (PDGF alpha receptor) to identify oligodendroglial progenitor cells in vivo and in vitro. It has recently become evident that the GD3 antigen, which has been widely used as a marker for oligodendrocyte progenitor cells, is also expressed by microglial cells. In this study we have examined the relationship between the NG2+/PDGF alpha receptor+ glial progenitor cells and microglial cells in normal developing and mature rat brain and in inflammatory lesions in mice with experimental autoimmune encephalomyelitis (EAE). Double-labeling of sections from normal rat brain using anti-NG2 antibodies and lectin from Griffonia simplicifolia (GSA I-B4) or monoclonal antibody 4H1 indicated that there is no overlap between NG2+ glial progenitor cells and microglia in the parenchyma of the central nervous system. In EAE lesions, both NG2+ cells and microglia, identified by antibodies to F4/80 and CD45, displayed reactive changes characterized by increased cell number and staining intensity and shortening and thickening of cell processes. Both cell types were found surrounding perivascular infiltrates of lymphocytes. Double-labeling EAE sections for NG2 and F4/80 or CD45 failed to reveal cells that co-expressed both antigens, suggesting that reactive NG2+ cells are distinct from activated microglia. However, a close spatial relationship between NG2+ cells and microglia was observed in the normal brain and to a greater extent in EAE, where processes of an activated microglial cell were sometimes seen to encircle an NG2+ cell. These observations are indicative of a functional interaction between microglia and the NG2+ glial cells.

Animals↗
PubMed1997

The RecD subunit of the RecBCD enzyme from Escherichia coli is a single-stranded DNA-dependent ATPase.

We have expressed the RecD subunit of the RecBCD enzyme from Escherichia coli as a fusion protein with a 31-amino acid NH2-terminal extension including 6 consecutive histidine residues (HisRecD). The overexpressed fusion protein can be purified in urea-denatured form by metal chelate affinity chromatography. The mixture of renatured HisRecD protein and the RecB and RecC proteins has a high level of ATP-dependent nuclease activity with either single- or double-stranded DNA, enhanced DNA unwinding activity, enhanced ATP hydrolysis activity in the presence of a small DNA oligomer cosubstrate, and chi-cutting activity. These are all characteristics of the RecBCD holoenzyme. The HisRecD protein by itself hydrolyzes ATP in the presence of high concentrations of single-stranded DNA (polydeoxythymidine). The activity is unstable at 37 degrees C, but is measurable at room temperature (about 23 degrees C). The HisRecD has very little ATPase activity in the presence of a much shorter single-stranded DNA (oligodeoxy(thymidine)12). HisRecD hydrolyzes ATP more efficiently than GTP and UTP, and has very little activity with CTP. We also purified a fusion protein containing a Lys to Gln mutation in the putative ATP-binding site of RecD. This mutant protein has no ATPase activity, indicating that the observed ATP hydrolysis activity is intrinsic to the RecD protein itself.

Adenosine Triphosphatases↗
PubMed1997

Diversity and plasticity of self recognition during the development of multiple sclerosis.

Recent studies using murine animal model systems indicate that clinical progression of autoimmune disease may be due to the sequential accumulation of neoautoreactivity characterized by extensive plasticity of self recognition. In the present study, we addressed the question of whether a similar paradigm of self recognition is implicated in the development of multiple sclerosis (MS), a demyelinating disease with a presumed autoimmune etiology. Our approach was to determine serial changes over a 12-18-mo period in response to an epitope-mapping series of 265 12-mer peptides of myelin proteolipid protein (PLP) by patients with isolated monosymptomatic demyelinating syndromes (IMDS), a group of distinct clinical disorders with variable rates of progression to MS. Our data showed that an extensive array of proteolipid protein peptides could elicit autoreactivity. Moreover, differential autoreactive patterns were evident within IMDS patient subpopulations. Monocentric monophasic IMDS patients with no evidence of prior subclinical disease typically showed fully sustained autoreactivity characterized by extensive plasticity, epitope focusing, shifting, and spreading of responses to new self determinants. In contrast, multicentric monophasic IMDS patients with putative evidence of prior asymptomatic lesion formation typically showed partially sustained autoreactivity characterized by abrupt abrogation of responses to an extensive array of self determinants. No sustained autoreactivity was observed in normal control subjects or in patients with other neurologic diseases. Our results indicate that self recognition associated with the development of MS is a developmental process characterized by autoreactive diversity, plasticity, and instability.

Adult↗
PubMed1997

Stabilization of ion selectivity filter by pore loop ion pairs in an inwardly rectifying potassium channel.

Ion selectivity is critical for the biological functions of voltage-dependent cation channels and is achieved by specific ion binding to a pore region called the selectivity filter. In voltage-gated K+, Na+ and Ca2+ channels, the selectivity filter is formed by a short polypeptide loop (called the H5 or P region) between the fifth and sixth transmembrane segments, donated by each of the four subunits or internal homologous domains forming the channel. While mutagenesis studies on voltage-gated K+ channels have begun to shed light on the structural organization of this pore region, little is known about the physical and chemical interactions that maintain the structural stability of the selectivity filter. Here we show that in an inwardly rectifying K+ (IRK) channel, IRK1, short range interactions of an ion pair in the H5 pore loop are crucial for pore structure and ion permeation. The two residues, a glutamate and an arginine, appear to form exposed salt bridges in the tetrameric channel. Alteration or disruption of such ion pair interactions dramatically alters ion selectivity and permeation. Since this ion pair is conserved in all IRK channels, it may constitute a general mechanism for maintaining the stability of the pore structure in this channel superfamily.

Amino Acid Sequence↗