Search PubMed⌕ Search

Biomedical subjects

M Yuan

Publications and source records attributed to M Yuan.

At least 37 records · Page 2Linked to original sources
PubMed2000

Amyloid beta interacts with the amyloid precursor protein: a potential toxic mechanism in Alzheimer's disease.

Amyloid beta protein (Abeta) deposition in the brain is a hallmark of Alzheimer's disease (AD). The fibrillar form of Abeta is neurotoxic, although the mechanism of its toxicity is unknown. We showed that conversion of Abeta to the fibrillar form markedly increased binding to specific neuronal membrane proteins, including amyloid precursor protein (APP). Nanomolar concentrations of fibrillar Abeta bound cell-surface holo-APP in cortical neurons. Reduced vulnerability of cultured APP-null neurons to Abeta neurotoxicity suggested that Abeta neurotoxicity involves APP. Thus Abeta toxicity may be mediated by the interaction of fibrillar Abeta with neuronal membrane proteins, notably APP. An Abeta-APP interaction reminiscent of the pathogenic mechanism of prions may thus contribute to neuronal degeneration in AD.

Alzheimer Disease↗
PubMed2000

Intelligent database generated occupational questionnaire system.

Obtaining an adequate occupational history requires special expertise to "ask the right questions" that are relevant to a particular patient's specific health conditions and potential exposures. This article describes a way to systematically accomplish this by means of a computer system that can overcome limited availability of necessary clinical occupational health expertise. The Intelligent Questionnaire system is a computer-based system for generating case-specific questionnaires about the influence of work on respiratory disease. Intelligent Questionnaire includes three databases: Questions, Responses, and Calls (clues to identify questions). The Questionnaire also arranges questions in a logical manner and provides a customized data entry screen for each subject. This approach provides primary practitioners with expertise on a case-by-case basis. It also facilitates occupational health surveillance because it allows acquiring detailed case-specific information in a systematic fashion. A computer-based system can facilitate obtaining occupational histories with high specificity and consistency without depending on general availability of a human occupational health clinical expertise.

Artificial Intelligence↗
PubMed2000

SHV-13, a novel extended-spectrum beta-lactamase, in Klebsiella pneumoniae isolates from patients in an intensive care unit in Amsterdam.

Eleven clonally related Klebsiella pneumoniae isolates were examined. These had been isolated at an intensive care unit in Amsterdam in 1994. Their resistance was associated with a conjugative 170-kb plasmid which encoded a novel SHV beta-lactamase designated SHV-13. The SHV-13 enzyme had two substitutions compared with SHV-1: Leu35Gln and Gly238Ala. It hydrolyzed cefotaxime much more rapidly than ceftazidime or aztreonam.

Anti-Bacterial Agents↗
PubMed2000

Body distribution of poly-DL-lactide-poly(ethylene glycol) microspheres with entrapped leptospira interrogans antigens following intravenous and oral administration to guinea-pigs.

Poly-DL-lactide-poly(ethylene glycol) (PELA) microspheres with entrapped antigens were administered intravenously and orally into guinea-pigs to quantitatively determine the in-vivo distribution and release profiles. PELA microspheres containing 125I-labelled outer-membrane protein Leptospira interrogans antigens (125I-OMP) were prepared by double-emulsion solvent extraction procedure, and characterized with respect to size, morphology and in-vitro release profiles. The fractured sections of liver and spleen were inspected by scanning electron microscopy, which indicated that microspheres had successfully been entrapped within the above tissues after intravenous injection and oral administration. At predetermined intervals, the blood and such tissues as the liver, spleen, kidney, thyroid, small intestine and mesentery were collected, and the radioactivity was measured by gamma scintillation counting. Following intravenous administration, 56.7% of administered microspheres were accumulated in immunization-related tissues, and 40.1% of microspheres were located in the liver and spleen. However, there was limited uptake efficiency (8.33%) following oral administration, and 49.5% of the absorbed microspheres were located in the intestinal mucosa. Compared with in-vitro release, the in-vivo release profiles of 125I-OMP from PELA microspheres, determined from the decreasing radioactivity in the above tissues, were much faster and the burst effect was higher. Antigen-loaded PELA microspheres were efficiently entrapped within immunization-related tissues after intravenous administration, but orally administered PELA microspheres showed limited uptake efficiency. Further investigation is needed to improve intestinal absorption.

Administration, Oral↗
PubMed1999

Proteolytic release and nuclear translocation of Notch-1 are induced by presenilin-1 and impaired by pathogenic presenilin-1 mutations.

The Notch family of proteins consists of transmembrane receptors that play a critical role in the determination of cell fate. Genetic studies in Caenorhabditis elegans suggest that the presenilin proteins, which are associated with familial Alzheimer's disease, regulate Notch signaling. Here we show that proteolytic release of the Notch-1 intracellular domain (NICD), an essential step in the activation of Notch signaling, is markedly reduced in presenilin-1 (PS1)-deficient cells and is restored by PS1 expression. Nuclear translocation of the NICD is also markedly reduced in PS1-deficient cells, resulting in reduced transcriptional activation. Mutations in PS1 that are associated with familial Alzheimer's disease impair the ability of PS1 to induce proteolytic release of the NICD and nuclear translocation of the cleaved protein. These results suggest that PS1 plays a central role in the proteolytic activation of the Notch-1-signaling pathway and that this function is impaired by pathogenic PS1 mutations. Thus, dysregulation of proteolytic function may underlie the mechanism by which presenilin mutations cause Alzheimer's disease.

Alzheimer Disease↗
PubMed1999

Investigation on process parameters involved in preparation of poly-DL-lactide-poly(ethylene glycol) microspheres containing Leptospira Interrogans antigens.

Block copolymer, poly-DL-lactide-poly(ethylene glycol) (PELA) with 11.5% of poly(ethylene glycol) (PEG) content was prepared by bulk ring-opening polymerization using stannous chloride as initiator. PELA microspheres with entrapped Leptospira Interrogans antigens, outer membrane protein (OMP) were elaborated by solvent extraction method based on the formation of multiple w/o/w emulsion, and the resulting microspheres were characterized with respect to particle size, OMP entrapment and morphology characteristics. The purpose of the present study is to perform the optimization of preparative parameters for OMP-loaded PELA micropsheres to control particle size and improve the OMP encapsulation efficiency. Of all the parameters investigated, the polymer concentration of organic phase and the external aqueous phase volume play major roles on particle size, while the organic phase volume, internal aqueous phase volume and the addition of surfactant into the internal aqueous phase display considerable effects on OMP loading efficiency. A small volume of internal aqueous phase and intermediate volumes of organic phase and external aqueous phase were favorable to achieve micropsheres with a size of 1-2 microns and high antigen encapsulation efficiency (70-80%). In vitro OMP release profiles from PELA microspheres consist of a small burst release followed by a gradual release phase. The OMP release rate shows some relations with the porous and water-swollen inner structure of the microspheres matrix. The presence of surfactant in microspheres accelerates OMP release, but the OMP entrapment within microspheres shows limited effects on the release profile.

Antigens, Bacterial↗
PubMed1999

Low-energy collisionally activated decomposition and structural characterization of cyclic heptapeptide microcystins by electrospray ionization mass spectrometry.

Characteristics of electrospray ionization mass spectrometry/collision-induced dissociation (ESIMS/CID) mass spectra of microcystins, cyanobacterial cyclic heptapeptide hepatoxins, were examined. The collision conditions showed remarkable effects on the quality of the CID mass spectra, which were divided into three patterns according to the number of Arg residues. A characteristic cleavage reaction and neutral losses of MeOH, NH3 and guanidine group(s) from the (2S,3S,8S,9S)-3-amino-9-methoxy-2,6,8-trimethyl-10-phenyldeca-4 E,6E-dienoic acid (Adda) and Arg residues were observed in the ESI and ESIMS/CID mass spectra, suggesting the most probable protonation sites in [M + H]+ and [M + 2H]2+ ions of microcystins. Microcystins with no Arg residue showed only [M + H]+ ions with a proton reacting at the methoxyl group in the Adda residue, and the ESIMS/CID/MS data revealed their structures unambiguously. The protonation site in [M + H]+ ions of microcystins with Arg residue(s) was the guanidine group. The [M + 2H]2+ ions of microcystins possessing one Arg residue had one proton on the Arg residue and probably another proton on the Adda residue, while the [M + 2H]2+ ions of microcystins having two Arg residues showed protonation at both Arg residues and the ESIMS/CID/MS data assigned their sequences. Structures of microcystins possessing one Arg residue can be assigned by ESIMS/CID/MS of [M + H]+ ions combined with those of [M + 2H]2+ ions.

Anabaena↗
PubMed1999

Electrospray ionization mass spectrometric analysis of microcystins, cyclic heptapeptide hepatotoxins: modulation of charge states and [M + H]+ to [M + Na]+ ratio.

Electrospray ionization mass spectrometry was used to develop a rapid, sensitive, and accurate method for determination and identification of hepatotoxic microcystins, cyanobacterial cyclic heptapeptides. To optimize the electrospray ionization conditions, factors affecting charge state distribution, such as amino acid components of sample, proton affinity of the additives, and additive concentration, were investigated in detail and a method for controlling charge states was developed to provide molecular-related ions for assignment of molecular weight and reasonably abundant precursor ions for MS/MS analysis. A procedure for identification of microcystins consisting of known amino acids was proposed: for microcystins giving abundant [M + 2H]2+ ions, the addition of nitrogen-containing bases to the aqueous sample solution is effective to obtain an increased intensity of [M + H]+ ions, whereas the addition of Lewis acids containing nitrogen can produce increased abundances of [M + 2H]2+ ions for microcystins giving weak [M + 2H]2+ ions. Microcystins possessing no arginine residue always give sodium adduct ions [M + Na]+ as the base peak, and these are difficult to fragment via low energy collision-induced dissociation to yield structurally informative products; the addition of oxalic acid increases [M + H]+ ion abundances, and these fragment readily.

Acetates↗
PubMed1999

Apoptosis induced by infection of primary brain cultures with diverse human immunodeficiency virus type 1 isolates: evidence for a role of the envelope.

Apoptosis of neurons and astrocytes is induced by human immunodeficiency type 1 (HIV-1) infection in vitro and has been demonstrated in brain tissue from patients with AIDS. We analyzed a panel of diverse HIV-1 primary isolates for the ability to replicate and induce neuronal and astrocyte apoptosis in primary human brain cultures. Apoptosis was induced three- to eightfold by infection with the blood-derived HIV-1 isolates 89.6, SG3, and ADA. In contrast, the brain-derived HIV-1 isolates YU2, JRFL, DS-br, RC-br, and KJ-br did not induce significant levels of apoptosis. The ability of HIV-1 isolates to induce apoptosis was independent of their replication capacity. Studies of recombinant chimeras between the SG3 and YU2 viruses showed that replacement of the YU2 Env with the SG3 Env was sufficient to confer the ability to induce apoptosis to the YU2 virus. Replacement of the Env V3 regions alone largely conferred the phenotypes of the parental clones. The SG3 Env used CXCR4 and CCR3 as coreceptors for virus entry, whereas YU2 used CCR5 and CCR3. The V3 regions of SG3 and YU2 conferred the ability to use CXCR4 and CCR5, respectively. In contrast, the 3' region of Env, particularly the C3V4 region, was required in conjunction with the V3 region for efficient use of CCR3. These results provide evidence that Env is a major determinant of neurodegenerative mechanisms associated with HIV-1 infection in vitro and raise the possibility that blood-derived viruses which emerge during the late stages of disease may affect disease progression in the central nervous system.

Animals↗
PubMed1999

[A clinical observation of krypton yellow laser photocoagulation for cystoid macular edema in nonproliferative diabetic retinopathy].

OBJECTIVE: To evaluate the clinical effects of krypton yellow laser photocoagulation for cystoid macular edema (CME) in nonproliferative diabetic retinopathy (NPDR). METHODS: 52 eyes (37 cases) with CME in NPDR were treated with local or grid macular krypton yellow photocoagulation, and according to the course they were divided into two groups: group I ( or= 7 months). The follow-up was 1 year. The visual acuity and the degree of macular edema in various period were analyzed and compared. RESULTS: The mean visual acuity was 0.27 +/- 0.21 before treatment and 0.53 +/- 0.26 after treatment (P < 0.01), 90.4% was increased, 5.8% was stable and 3.8% was decreased. CME disappeared completely in 55.8% of the patients, disappeared partially in 42.3% and stable in 1.9%. In group I the visual acuity was improved in 81.5% of the patients at post-treatment 1 month; at post-treatment 6 months, the visual acuity was increased in 100% of the cases, CME disappeared completely in 70.4% and disappeared partially in 29.6%. In group II, the visual acuity was improved in 20% of the patients at post-treatment 1 month, and at post-treatment 6 months in 88%, CME disappeared completely in 40% and disappeared partially in 56%. The differences in the rate of visual recovery and therapeutic effects between the two groups were statistically significant (P < 0.01). CONCLUSIONS: Krypton yellow laser is prominently effective and selective for CME in NPDR. The effects are related to the course of the disease, and the therapeutic results are better in cases receiving early treatment.

Adult↗
PubMed1998

Characterization of mutations in the cystathionine beta-synthase gene in Irish patients with homocystinuria.

We used single-strand conformational polymorphism and nucleotide sequencing to characterize defective cystathionine beta-synthase gene alleles in 18 independent Irish patients with homocystinuria. Six mutations were detected, three of which have been reported previously and three of which were novel. The novel mutations include T302C (L101P), C684G (N228K), and G1063C (A354P). Of the three, only T302C (L101P) was somewhat prevalent, being found in 3 of 37 independent alleles.

Cystathionine beta-Synthase↗
PubMed1998

Seven new microcystins possessing two L-glutamic acid units, isolated from Anabaena sp. strain 186.

Electrospray ionization mass spectrometry has been applied to the structure assignment of seven new microcystins (1-7), obtained from cultured Anabaena sp. strain 186. The seven new microcystins contain the dehydroalanine (Dha) or L-Ser unit instead of the N-methyldehydroalanine unit and the L-Glu and/or its delta-methyl ester [E(OMe)] units at the two variable L-amino acid units, and the structures were assigned as [Dha7]microcystin-E(OMe)E(OMe) (1), [D-Asp3,Dha7]microcystin-E(OMe)E(OMe) (2), [L-Ser7]microcystin-E(OMe)E(OMe) (3), [D-Asp3,L-Ser7]microcystin-E(OMe)E(OMe) (4), [Dha7]microcystin-EE(OMe) (5), [D-Asp3,Dha7]microcystin-EE(OMe) (6), and [L-Ser7]microcystin-EE(OMe) (7). These microcystins are the first examples containing dicarboxylic amino acids at the two variable L-amino acid units in microcystins.

Anabaena↗
PubMed1998

Aging renders the brain vulnerable to amyloid beta-protein neurotoxicity.

The formation of fibrillar deposits of amyloid beta protein (Abeta) in the brain is a pathological hallmark of Alzheimer's disease (AD). A central question is whether Abeta plays a direct role in the neurodegenerative process in AD. The involvement of Abeta in the neurodegenerative process is suggested by the neurotoxicity of the fibrillar form of Abeta in vitro. However, mice transgenic for the Abeta precursor protein that develop amyloid deposits in the brain do not show the degree of neuronal loss or tau phosphorylation found in AD. Here we show that microinjection of plaque-equivalent concentrations of fibrillar, but not soluble, Abeta in the aged rhesus monkey cerebral cortex results in profound neuronal loss, tau phosphorylation and microglial proliferation. Fibrillar Abeta at plaque-equivalent concentrations is not toxic in the young adult rhesus brain. Abeta toxicity in vivo is also highly species-specific; toxicity is greater in aged rhesus monkeys than in aged marmoset monkeys, and is not significant in aged rats. These results suggest that Abeta neurotoxicity in vivo is a pathological response of the aging brain, which is most pronounced in higher order primates. Thus, longevity may contribute to the unique susceptibility of humans to Alzheimer's disease by rendering the brain vulnerable to Abeta neurotoxicity.

Aging↗
PubMed1998

Epidemiological typing of klebsiellae with extended-spectrum beta-lactamases from European intensive care units.

Extended-spectrum beta-lactamases (ESBLs) are an increasing cause of resistance to oxyimino-aminothiazolyl cephalosporins, especially in klebsiellae. In a recent survey we detected ESBLs in 220 (23%) of 966 consecutive klebsiellae from 35 intensive care units (ICUs) in southern and western Europe. The present study examined the extent to which this distribution reflected epidemic strain spread, as against the distribution of ESBL genes into unrelated strains. All 220 ESBL producers were subjected to capsular serotyping and pulsed-field gel DNA electrophoresis (PFGE). Beta-Lactamases were typed for strains isolated on three or more occasions, with the emphasis on SHV enzymes, as these were commoner than TEM variants. Serotyping and PFGE typing defined 85 distinct strains, from 23 of the 35 participating centres. Of 14 centres that contributed five or more ESBL producers, all sent representatives of more than one strain, and two centres sent members of ten or more different strains in contributions of 17-21 ESBL-producing isolates. Nevertheless, epidemic strains-defined as those represented by three or more isolates-accounted for a majority (61%) of the collection. Fifty-two isolates of the same serotype K25 (occasionally acapsular) strain with SHV-4 beta-lactamase were recovered at two French hospitals and one in Belgium. This strain has been found by others in France, and has become particularly widespread. Another single strain was found in two separate Portuguese centres, and many individual hospitals had one or more epidemic strain(s), as well as a scatter of diverse ESBL producers. Major variation in antibiogram and plasmid profile was apparent within strains, with some intra-strain variation in beta-lactamase type. These data imply a fluid situation, with resistance determinants being gained, modified or lost. The endemicity of ESBL producers is disturbing since it limits the potential for control by blocking strain spread, while the diversity within strains is disturbing because it complicates the design of antibiotic policies even during 'single strain' outbreaks.

Anti-Bacterial Agents↗
PubMed1998

Interactions of beta-lactamases with sanfetrinem (GV 104326) compared to those with imipenem and with oral beta-lactams.

Sanfetrinem is a trinem beta-lactam which can be administered orally as a hexatil ester. We examined whether its beta-lactamase interactions resembled those of the available carbapenems, i.e., stable to AmpC and extended-spectrum beta-lactamases but labile to class B and functional group 2f enzymes. The comparator drugs were imipenem, oral cephalosporins, and amoxicillin. MICs were determined for beta-lactamase expression variants, and hydrolysis was examined directly with representative enzymes. Sanfetrinem was a weak inducer of AmpC beta-lactamases below the MIC and had slight lability, with a kcat of 0.00033 s(-1) for the Enterobacter cloacae enzyme. Its MICs for AmpC-derepressed E. cloacae and Citrobacter freundii were 4 to 8 microg/ml, compared with MICs of 0.12 to 2 microg/ml for AmpC-inducible and -basal strains; MICs for AmpC-derepressed Serratia marcescens and Morganella morganii were not raised. Cefixime and cefpodoxime were more labile than sanfetrinem to the E. cloacae AmpC enzyme, and AmpC-derepressed mutants showed much greater resistance; imipenem was more stable and retained full activity against derepressed mutants. Like imipenem, sanfetrinem was stable to TEM-1 and TEM-10 enzymes and retained full activity against isolates and transconjugants with various extended-spectrum TEM and SHV enzymes, whereas these organisms were resistant to cefixime and cefpodoxime. Sanfetrinem, like imipenem and cefixime but unlike cefpodoxime, also retained activity against Proteus vulgaris and Klebsiella oxytoca strains that hyperproduced potent chromosomal class A beta-lactamases. Functional group 2f enzymes, including Sme-1, NMC-A, and an unnamed enzyme from Acinetobacter spp., increased the sanfetrinem MICs by up to 64-fold. These enzymes also compromised the activities of imipenem and amoxicillin but not those of the cephalosporins. The hydrolysis of sanfetrinem was examined with a purified Sme-1 enzyme, and biphasic kinetics were found. Finally, zinc beta-lactamases, including IMP-1 and the L1 enzyme of Stenotrophomonas maltophilia, conferred resistance to sanfetrinem and all other beta-lactams tested, and hydrolysis was confirmed with the IMP-1 enzyme. We conclude that sanfetrinem has beta-lactamase interactions similar to those of the available carbapenems except that it is a weaker inducer of AmpC types, with some tendency to select derepressed mutants, unlike imipenem and meropenem.

Anti-Bacterial Agents↗
PubMed1998

[Experimental study of the therapeutic effects of an anti-endothelial cell monoclonal antibody BVE-1 for solid tumor xenograft in nude mice].

OBJECTIVE: To study the possibility of targeting endothelial cells with monoclonal antibody for the therapy of solid tumors. METHODS: Leiomyosarcoma cell line SK-LMS-1, liver cancer cell line 7721 and pancreatic cancer cell line SW1990 xenografts in nude mice were treated i.p. with an anti-endothelial cell monoclonal antibody BVE-1 or 131I labeled BVE-1, with normal mouse IgG or 131I labeled IgG as controls. The tumor volume was measured at regular intervals following treatment. After sacrifice of the mice, the tumor was histologically examined and the intra-tumoral microvessel density(TMVD) recorded. RESULTS: The tumor growth inhibition effects in mice treated with BVE-1 was 49.8% in SK-LMS-1, 48.7% in SW1990 and 70.5% in 7721, respectively. Metastasis of leiomyosarcoma was also inhibited by the antibody treatment, leading to decreased death rate. This effect was enhanced when treated with 131I-labeled BVE-1 with an increase of tumor growth inhibition rate to 82.2%-86.6%. Pathologically, capillary endothelial cells degeneration, occlusion of capillaries and massive tumor cells necrosis around the degenerated vessels were observed in the BVE-1 treated mice. TMVD was significantly lower in the BVE-1 treated mice than that in mice treated with normal mouse IgG and in the untreated mice. CONCLUSION: The monoclonal antibody against vascular endothelial cells BVE-1 is effective in the treatment of human cancer xeno-transplanted in nude mice through the induction of capillary endothelial degeneration and vascular occlusion inside of the tumor. It can be used as a novel strategic approach in the treatment of human solid tumors.

Animals↗
PubMed1998

[In vivo inductive effect of hemin on the erythroid progenitor of the normal and aplastic anemia mice].

OBJECTIVE: To investigate the in vivo effect of hemin on erythroid progenitor of the normal and aplastic anemia mice. METHODS: BFU-E and CFU-E of normal and aplastic anemia(AA) mice were assayed at different time (6 h, 12 h and 24 h) after hemin injection on a dosage of 6.50 micrograms/g body weight, and at 6 h after injection of different doses of hemin (0.65 microgram/g, 6.50 micrograms/g and 13.00 micrograms/g body weight). RESULTS: The yields of BFU-E and CFU-E from AA mice were reduced compared with that from normal mice. At 6 h after hemin injection (6.50 micrograms/g b.w.), the yields of BFU-E and CFU-E from AA mice were increased from 3 +/- 2/femur and 12 +/- 3/femur to 10 +/- 2/femur (P < 0.01) and 39 +/- 12/femur (P < 0.01), respectively, and so did the case for normal mice (for BFU-E, from 1,056 +/- 160/femur to 3,410 +/- 708/femur, P < 0.01, and for CFU-E, from 12 +/- 3/five 200x fields to 38 +/- 3/five 200x fields, P < 0.01). Low dose of hemin had no inductive effect. CONCLUSION: Hemin is a in vivo inducer of erythroid progenitors both in normal and AA mice.

Anemia, Aplastic↗