Biomedical subjects

Y Gu

Publications and source records attributed to Y Gu.

At least 109 records · Page 6Linked to original sources

PubMed2001

Anatomic basis of vascularized ulnar nerve graft by the pedicle of the superior collateral ulnar artery.

OBJECTIVE: To investigate the anatomic basis of vascularized ulnar nerve graft by the pedicle of the superior collateral ulnar artery (SCUA). METHODS: Twenty-two fresh cadaver upper extremities injected i ntra-arterially with latex were dissected to study the extrinsic blood supply of the ulnar nerve. Other 6 fresh upper extremities were used to analyze the blood supply range of SCUA inside the ulnar nerve by microangiographic and histological methods. RESULTS: The ulnar nerve was supplied by a branch of the lateral thoracic artery or directly by the axillary artery in the axillary section, by b ranches of SCUA in the upper arm, and by branches from the anastomosis of the collateral arteries and the posterior branch of the recurrent ulnar artery in the elbow. SCUA could supply the whole ulnar nerve from the axilla to the wrist. CONCLUSIONS: The ulnar nerve can be used as a vascularized nerve graft by the pedicle of SCUA in treatment of brachial plexus roots avulsion by C7 transfer from healthy side.

Humans↗

PubMed2001

[Effect of manganese on the ratio of micronucleus cells in mice marrow].

The ratio of micronucleus in the bone marrow cell of mice induced by manganese (Mn2+, MnCl2) through intraperitoneal injection at doses of 0, 25, 50 and 100 mg/kg respectively was investigated. The number of micronucleus cells per 1000 polychromatic erythrocyte (PCE) from breast bone marrow was counted. The results showed that micronucleus ratio in bone marrow cells were 12.0 and 16.4 per 1000 in the medium and high dosage groups, which were higher than that of control (P < 0.01). There is no distinct difference between the low dosage group and the control group (P > 0.05), but show a rising trend with the dosage of Mn2+. It indicated that the higher the dose of MnCl2, the stronger the toxic effect to the micronucleus in bone marrow cells. MnCl2 is considered having mutation to chromosome and potential heredity toxicity.

Animals↗

PubMed2001

[A comparative observation preoperatively and postoperatively of nasal mucosa in chronic sinusitis treated with endoscopic sinus surgery].

OBJECTIVES: To study morphologic and functional mucosal changes both preoperatively and postoperatively in chronic sinusitis (CS) treated with endoscopic sinus surgery (ESS). METHODS: 1. Saccharin test and light microscopic examination of nasal mucosa were taken preoperatively and postoperatively in 32 cases with CS and in 28 normal subjects as control. 2. Scanning and transmission electron microscopy were performed to exam preoperatively and postoperatively the nasal mucosa in 10 cases with CS and in 2 normal cases as control. RESULTS: 1. The preoperative saccharin test time (STT) in patients with CS was significantly longer than that in the controls (P < 0.001), and the postoperative STT became significantly shorter than that in preoperative one(P < 0.001). 2. The pathological changes of nasal mucosa, such as infiltration in inflammatory cells, edema, polypoid formations and pathologic glands were observed preoperatively. The infiltration in inflammatory cells, edema and polypoid formations were significantly released (P < 0.01) at four months after operation, and there was no significant difference comparing with the controls (P > 0.05). However, the pathologic glands were not reduced even after four months postoperatively. 3. The examination of electron microscopy demonstrated that the ultrastructure of nasal mucosa was impaired preoperatively and almost completely recovered at four months postoperatively. CONCLUSIONS: The normal structure and clearance function of nasal mucosa in patients with CS was impaired preoperatively, and the impaired structure and mucociliary clearing function of nasal mucosa were greatly improved after ESS and almost completely recovered at four months postoperatively. The pathologic glands and secretive function of nasal mucosa may need longer period for recovering.

Adolescent↗

PubMed2000

The chaperone protein BiP binds to a mutant prion protein and mediates its degradation by the proteasome.

Familial prion diseases are thought to result from a change in structure of the mutant prion protein (PrP), which takes a pathogenic conformation. We have examined the role of molecular chaperones in the folding of normal and mutant PrP Q217R (PrP(217)) in transfected neuroblastoma cells. In a previous report we showed that, although most of the PrP(217) forms escape the endoplasmic reticulum quality control system and aggregate in post-Golgi compartments, a significant proportion of PrP(217) retains the C-terminal glycosylphosphatidyl inositol signal peptide (PrP32), and does not exit the endoplasmic reticulum (Singh, N., Zanusso, G., Chen, S. G., Fujioka, H., Richardson, S., Gambetti, P., and Petersen, R. B. (1997) J. Biol. Chem. 272, 28461-28470). We have now studied the folding and turnover of PrP32 to understand the mechanism by which abnormal PrP forms cause cellular toxicity in our cell culture model and in the human brain carrying the Gerstmann-Sträussler-Scheinker disease Q217R mutation. In this report, we show that PrP32 remains associated with the chaperone BiP for an abnormally prolonged period of time and is degraded by the proteasomal pathway. This study is the first demonstration that BiP is chaperoning the folding of PrP and plays a role in maintaining the quality control in the PrP maturation pathway. Our data provide new insight into the diverse pathways of mutant PrP metabolism and neurotoxicity.

Amino Acid Substitution↗

PubMed2000

Insulin prevents cardiomyocytes from oxidative stress-induced apoptosis through activation of PI3 kinase/Akt.

BACKGROUND: Loss of cardiomyocytes by apoptosis is proposed to cause heart failure. Reactive oxygen species induce apoptosis in many types of cells including cardiomyocytes. Because insulin has been reported to have protective effects, we examined whether insulin prevents cardiomyocytes from oxidative stress-induced apoptotic death. METHODS AND RESULTS: Cultured cardiomyocytes of neonatal rats were stimulated by hydrogen peroxide (H(2)O(2)). Apoptosis was evaluated by means of the TUNEL method and DNA laddering. Incubation with 100 micromol/L H(2)O(2) for 24 hours increased the number of TUNEL-positive cardiac myocytes (control, approximately 4% versus H(2)O(2), approximately 23%). Pretreatment with 10(-)(6) mol/L insulin significantly decreased the number of H(2)O(2)-induced TUNEL-positive cardiac myocytes (approximately 12%) and DNA fragmentation induced by H(2)O(2). Pretreatment with a specific phosphatidylinositol 3 kinase (PI3K) inhibitor, wortmannin, and overexpression of dominant negative mutant of PI3K abolished the cytoprotective effect of insulin. Insulin strongly activated both PI3K and the putative downstream effector AKT: Moreover, a proapoptotic protein, BAD:, was significantly phosphorylated and inactivated by insulin through PI3K. CONCLUSIONS: These results suggest that insulin protects cardiomyocytes from oxidative stress-induced apoptosis through the PI3K pathway.

Animals↗

PubMed2000

Observation of saturn-ring defects around solid microspheres in nematic liquid crystals

We report an experimental system based on rigid, monodisperse, microparticles with tunable surface properties for the study of topological defects that form about dispersed solid phases in anisotropic media. We clearly observe equatorial Saturn-ring defects to form a distance (0.09+/-0.01)R from the surface of isolated microspheres (with strong homeotropic anchoring) dispersed in nematic phases. These defects, some of which are observed to be stable for up to a month, are similar in size to past theoretical predictions (with strong homeotropic anchoring) and can be reversibly expanded in an electric field.

Journal Article↗

PubMed2000

Human homolog of the MutY repair protein (hMYH) physically interacts with proteins involved in long patch DNA base excision repair.

The human MutY homolog (hMYH) is a DNA glycosylase involved in the removal of adenines or 2-hydroxyadenines misincorporated with template guanines or 7,8-dihydro-8-oxodeoxyguanines. hMYH is associated in vivo with apurinic/apyrimidinic endonuclease (APE1), proliferating cell nuclear antigen (PCNA), and replication protein A (RPA) in HeLa nuclear extracts as shown by immunoprecipitation and Western blotting. However, binding of hMYH to DNA polymerases beta and delta was not detected. By using constructs containing different portions of hMYH fused to glutathione S-transferase, we have demonstrated that the APE1-binding site is at a region around amino acid residue 300, that the PCNA binding activity is located at the C terminus, and that RPA binds to the N terminus of hMYH. A peptide consisting of residues 505-527 of hMYH that contains a conserved PCNA-binding motif binds PCNA, and subsequent amino acid substitution identified Phe-518 and Phe-519 as essential residues required for PCNA binding. RPA binds to a peptide that consists of residues 6-32 of hMYH and contains a conserved RPA-binding motif. The PCNA- and RPA-binding sites of hMYH are further confirmed by peptide and antibody titration. These results suggest that hMYH repair is a long patch base excision repair pathway.

Amino Acid Motifs↗

PubMed2000

Using a Bayesian belief network to aid differential diagnosis of tropical bovine diseases.

The examination of presenting signs has always played an important role in the diagnosis of diseases in animal populations. In the case of diseases of tropical cattle, such expertise is often scarce and confined to those experts with many years of experience. To capture, conserve and disseminate such valuable expert knowledge remains a key challenge to the application of knowledge-based systems in veterinary medicine. In this communication, we explore the use of a Bayesian belief network to quantify expert opinion with a view to estimating the likelihood of various diseases in the presence and absence of certain signs. Information was elicited from a panel of 44 experienced veterinarians to provide the response matrix of 27 signs associated with 20 commonly occurring diseases in sub-Saharan cattle. Using this prior information, estimates of the probability of certain signs occurring with each disease were calculated from which the Bayesian belief network was able to propagate the posterior probability of each of the diseases based on the observed signs. The method as an aid in making diagnosis is discussed. It is recognised that such an approach is but one strand in the process of arriving at a diagnosis. For ease of use and accessibility, the approach has been converted into the software program CaDDiS (Cattle Disease Diagnosis System) which is available for consultation on the World Wide Web.

Animals↗

PubMed2000

Expression of functional metabotropic glutamate receptors in primary cultured rat osteoblasts. Cross-talk with N-methyl-D-aspartate receptors.

Osteoblasts and osteoclasts express functional N-methyl-d-aspartate (NMDA) receptors, which participate in regulation of bone matrix. In rat femoral osteoblasts held in whole cell clamp there is a robust NMDA current but little if any response to l-glutamate. We have investigated expression of metabotropic glutamate receptors (mGluRs) in these cells. By reverse transcription polymerase chain reaction, we have detected expression of mGluR1b (but not mGluR1a, 2, 3, 4, 5, or 6). Blockade of mGluRs with (+/-)-alpha-methyl-carboxyphenyl-glycine resulted in an enlarged l-glutamate-induced current that resembled the response to NMDA. Conversely, prior stimulation of mGluRs with trans-(+/-)-1-amino-1, 3-cyclopentanedicarboxylic acid (1S,3R-ACPD; mGluR agonist) reduced the NMDA-induced current by 77%. Monitoring of [Ca(2+)](i) showed that NMDA induced a sustained elevation of [Ca(2+)](i), which was dependent upon [Ca(2+)](o). Treatment with 1S,3R-ACPD generated an initial transient that was independent of [Ca(2+)](o), followed by a sustained, [Ca(2+)](o)-dependent phase, a response consistent with phospholipase C-mediated mobilization of stored Ca(2+). Investigations of the interaction between the two receptors confirmed inhibitory modulation of the NMDA receptor-induced rise in [Ca(2+)](i) by mGluRs. Parathyroid hormone, which also activates phospholipase C in osteoblasts, had a similar inhibitory effect on the NMDA receptor-induced [Ca(2+)](i) response. Elevation of [Ca(2+)](i) mediated by mGluR activation was reduced by subsequent stimulation of NMDA receptors. This is the first description of mGluRs in bone and shows that complex glutamatergic signaling can occur in this tissue.

Animals↗

PubMed2000

The Electrical Double-Layer Interaction between a Spherical Particle and a Cylinder.

Based on the well-known Debye-Hückel approximation and the Derjaguin's integration method, this paper presents an integral solution for the electrical double-layer (EDL) interaction between a spherical particle and a cylinder. The effects of the relative dimensions of the cylinder to the sphere on the EDL interaction are studied using this numerical solution. The detailed numerical results indicate that, in general, the curvature effect on the EDL interaction cannot be neglected at small separation distances. The widely used sphere-flat plate approximation will considerably overestimate the actual EDL interaction between a spherical particle and a cylinder. The ratio of the radius of the particle to the EDL thickness, tau=kappaa(p), also plays an important role in determining the EDL interaction at small dimensionless separation distances (</=3tau(-1)). In addition, it is found that at small separation distances, the EDL interaction can become attractive between two asymmetric EDLs, even though their zeta potentials have the same polarity. Copyright 2000 Academic Press.

Journal Article↗

PubMed2000

Fourier-transform Raman and infrared spectroscopic analysis of novel biliverdin compounds.

The vibrational spectroscopy of novel biliverdin compounds were studied by Fourier-transform Raman (FT-Raman) and infrared (FT-IR) spectroscopy. The effects of type, length and position of substituents at C(8) and C(12) or C(1) and C(19) of tetrapyrroles on FT-Raman and FT-IR spectra of these compounds, are discussed. The marker bands are developed in order to distinguish between etiobiliverdin and mesobiliverdin.

Biliverdine↗

PubMed2000

Residue R216 and catalytic efficiency of a murine class alpha glutathione S-transferase toward benzo[a]pyrene 7(R),8(S)-diol 9(S), 10(R)-epoxide.

Murine class alpha glutathione S-transferase A1-1 (mGSTA1-1), unlike mammalian class alpha GSTs, is the most efficient in the glutathione (GSH) conjugation of the ultimate carcinogenic metabolite of benzo[a]pyrene, (+)-anti-7,8-dihydroxy-9,10-oxy-7,8,9, 10-tetrahydrobenzo[a]pyrene [(+)-anti-BPDE] [Hu, X., Srivastava, S. K., Xia, H., Awasthi, Y. C., and Singh, S. V. (1996) J. Biol. Chem. 271, 32684-32688]. Here, we report the crystal structures of mGSTA1-1 in complex with GSH and with the GSH conjugate of (+)-anti-BPDE (GSBpd) at 1.9 and 2.0 A resolution, respectively. Both crystals belong to monoclinic space group C2 with one dimer in the asymmetric unit. The structures reveal that, within one subunit, the GSH moiety interacts with residues Y8, R14, K44, Q53, V54, Q66, and T67, whereas the hydrophobic moiety of GSBpd interacts with the side chains of F9, R14, M207, A215, R216, F219, and I221. In addition, the GSH moiety interacts with D100 and R130 from the other subunit across the dimer interface. The structural comparison between mGSTA1-1.GSH and mGSTA1-1.GSBpd reveals significant conformational differences. The movement of helix alpha9 brings the residues on the helix into direct interaction with the product. Most noticeable are the positional displacement and conformational change of R216, one of the residues located in helix alpha9. The side chain of R216, which points away from the H-site in the mGSTA1-1.GSH complex, probes into the active site and becomes parallel with the aromatic ring system of GSBpd. Moreover, the guanidinium group of R216 shifts approximately 8 A and forms a strong hydrogen bond with the C8 hydroxyl group of GSBpd, suggesting that the electrostatic assistance provided by the guanidinium group facilitates the ring-opening reaction of (+)-anti-BPDE. The structure of mGSTA1-1. GSBpd is also compared with those of hGSTP1-1[V104,A113].GSBpd, hGSPA1-1.S-benzylglutathione, and mGSTA4-4. 4-S-glutathionyl-5-pentyltetrahydrofuran-2-ol. The comparison provides further evidence that supports the functional roles of R216 and helix alpha9. The lack of mobility of helix alpha9 and/or the lack of electrostatic assistance from R216 may be responsible for the relatively lower activity of hGSTA1-1, mGSTA4-4, and hGSTP1-1 toward (+)-anti-BPDE.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

PubMed2000

Nitric oxide is neither necessary nor sufficient for resolution of Plasmodium chabaudi malaria in mice.

Malaria is a life-threatening re-emerging disease, yet it is still not clear how bloodstage malarial parasites are killed. Nitric oxide (NO), which has potent anti-microbial activity, may represent an important killing mechanism. The production of NO during descending Plasmodium chabaudi parasitemia, a period when parasites are killed by the immune response, supports this concept. However, NOS20/0 and NOS30/0 mice as well as mice treated with NO synthase 2 (NOS2) inhibitors do not develop exacerbated malaria, indicating that NO production is not necessary for the suppression of P. chabaudi parasitemia. It is possible due to the plasticity in the immune response during malaria that Ab-mediated immunity is enhanced in the absence of NO, thereby explaining the lack of exacerbated malaria in NOS-deficient mice even though NO may function in protection. However, NOS2- and B cell-deficient mice, which cannot use Ab-mediated immunity, suppress their parasitemia with a similar time course as B cell-deficient controls. C57BL/6 mice treated with Propionibacterium acnes to elicit high levels of macrophage-derived NO have a similar time course of P. chabaudi parasitemia as P. acnes-treated NOS20/0 mice, which do not produce NO; this indicates that NO is not sufficient for parasite killing. Collectively, these results indicate that NO is not necessary or sufficient to resolve P. chabaudi malaria.

Animals↗

PubMed2000

Purification and characterization of a mammalian homolog of Escherichia coli MutY mismatch repair protein from calf liver mitochondria.

A protein homologous to the Escherichia coli MutY glycosylase, referred to as mtMYH, has been purified from calf liver mitochondria. SDS-polyacrylamide gel electrophoresis, western blot analysis as well as gel filtration chromatography predicted the molecular mass of the purified calf mtMYH to be 35-40 kDa. Gel mobility shift analysis showed that the purified mtMYH formed specific binding complexes with A/8-oxoG, G/8-oxoG and T/8-oxoG, weakly with C/8-oxoG, but not with A/G and A/C mismatches. The purified mtMYH exhibited DNA glycosylase activity removing adenine mispaired with G, C or 8-oxoG and weakly removing guanine mispaired with 8-oxoG. The mtMYH glycosylase activity was insensitive to high concentrations of NaCl and EDTA. The purified mtMYH cross-reacted with antibodies against both intact MutY and a peptide of human MutY homolog (hMYH). DNA glycosylase activity of mtMYH was inhibited by anti-MutY antibodies but not by anti-hMYH peptide antibodies. Together with the previously described mitochondrial MutT homolog (MTH1) and 8-oxoG glycosylase (OGG1, a functional MutM homolog), mtMYH can protect mitochondrial DNA from the mutagenic effects of 8-oxoG.

Animals↗

PubMed2000

Dominant negative mutation of the hematopoietic-specific Rho GTPase, Rac2, is associated with a human phagocyte immunodeficiency.

Rho GTPases control a variety of cellular processes, including actin polymerization, integrin complex formation, cell adhesion, gene transcription, cell cycle progression, and cell proliferation. A patient is described who has recurrent infections and defective neutrophil cellular functions similar to those found in Rac2-deficient mice. Molecular methods were used to clone the expressed Rac2 cDNA from this patient, and a single base pair change (G-->A at nucleotide 169) in the coding sequence was identified. This results in an asparagine for aspartic acid mutation at amino acid 57 (D57N), a residue that is involved in nucleotide binding and is conserved in all mammalian Rho GTPases. The cloned cDNA was then introduced into normal bone marrow cells through retrovirus vectors, and neutrophils expressing this mutant exhibited decreased cell movement and production of superoxide in response to fMLP. The expressed recombinant protein was also analyzed biochemically and exhibited defective binding to GTP. Functional studies demonstrated that the D57N mutant behaves in a dominant-negative fashion at the cellular level. The syndrome of Rac2 dysfunction represents a human condition associated with mutation of a Rho GTPase and is another example of human disease associated with abnormalities of small G protein signaling pathways. (Blood. 2000;96:1646-1654)

3T3 Cells↗

PubMed2000

Mitochondrial basis for immune deficiency. Evidence from purine nucleoside phosphorylase-deficient mice.

We generated purine nucleoside phosphorylase (PNP)-deficient mice to gain insight into the mechanism of immune deficiency disease associated with PNP deficiency in humans. Similar to the human disease, PNP deficiency in mice causes an immunodeficiency that affects T lymphocytes more severely than B lymphocytes. PNP knockout mice exhibit impaired thymocyte differentiation, reduced mitogenic and allogeneic responses, and decreased numbers of maturing thymocytes and peripheral T cells. T lymphocytes of PNP-deficient mice exhibit increased apoptosis in vivo and higher sensitivity to gamma irradiation in vitro. We propose that the immune deficiency in PNP deficiency is a result of inhibition of mitochondrial DNA repair due to the accumulation of dGTP in the mitochondria. The end result is increased sensitivity of T cells to spontaneous mitochondrial DNA damage, leading to T cell depletion by apoptosis.

Animals↗

PubMed2000

Evidence that collapsin response mediator protein-2 is involved in the dynamics of microtubules.

Collapsin response mediator protein-2 (CRMP-2) is a member of the CRMP/TOAD/Ulip/DRP family of cytosolic phosphoproteins involved in neuronal differentiation and axonal guidance. CRMP-2 mediates the intracellular response to collapsin 1/semaphorin 3A, a repulsive extracellular guidance cue for axonal outgrowth. The mutation of UNC-33, a Caenorhabditis elegans homolog of CRMP-2, results in abnormality of microtubules in neurites, but the mechanism of CRMP-2 action remains to be clarified. Here, we report that overexpression of human CRMP-2 in Neuro2a cells, a mouse neuroblastoma cell line, results in blebbing of the cytoplasm. Furthermore, some cells exhibited intranuclear inclusions, which were labeled with antibodies to CRMP-2 and tubulin. CRMP-2 was found to be associated with microtubule bundles in the spindles at the metaphase and in the midbodies at the late telophase in mitotic cells. Thus, it is most likely that failure of complete disassembly of the spindle microtubules during mitosis is responsible for the formation of these intranuclear inclusions. We suggest that CRMP-2 functions by regulating the dynamics of microtubules.

Acetylation↗

PubMed2000

Neurofibrillary tangle-associated collapsin response mediator protein-2 (CRMP-2) is highly phosphorylated on Thr-509, Ser-518, and Ser-522.

3F4, a monoclonal antibody raised against partially purified paired helical filaments (PHFs), strongly labeled neurofibrillary tangles and some plaque neurites but barely labeled neuropil threads. The levels of the 65-kDa antigen were significantly increased in the soluble fraction of the brains affected by Alzheimer's disease (AD), as compared with that in the case of control brains. The antigen was previously identified as human collapsin response mediator protein-2 (hCRMP-2) by sequencing the immunoaffinity-purified 65-kDa antigen [Yoshida, H., Watanabe, A., and Ihara, Y. (1998) J. Biol. Chem. 273, 9761-9768]. Here, we show that the 3F4 antigen represents a highly phosphorylated form of CRMP-2. The 3F4-reactive phosphoepitope was localized to the carboxyl-terminal portion of hCRMP-2, and was created by a novel 45-50-kDa protein kinase in rat brain extract. Site-directed mutagenesis of this portion showed that multiple sites of CRMP-2 are differentially phosphorylated within residues 507-522, and that phosphorylation of three sites, Thr-509, Ser-518, and Ser-522, is required for full 3F4 binding. The phosphorylation of this particular portion carboxyl-terminal to the basic region of CRMP-2 may play an important role in regulating its activity, and may be involved in the formation of degenerating neurites in AD brain.

Alzheimer Disease↗