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Biomedical subjects

Q Yu

Publications and source records attributed to Q Yu.

At least 19 recordsLinked to original sources
PubMed2002

Enzymatic hydrolysis of waste sugarcane bagasse in water media.

Enzymatic hydrolysis of natural cellulose such as sugarcane bagasse is usually carried out in a buffer medium. In this paper, the enzymatic hydrolysis of a waste sugarcane bagasse in water media was carried out.The bagasse was pre-treated with heating explosion and pure (ion exchange), reverse-osmosis and tap water media were used in place of a buffer solution in the hydrolysis process. The yields for reducing sugars and the changes in solution pH and electric conductivity during the hydrolysis under various conditions were studied. The results were also compared with those obtained in buffer solutions. Similar levels of sugar yields were obtained in water and buffer solution media. The pH of the hydrolyzate was in the range of 4.5 - 5.0, which coincided with the optimum pH for the enzyme reaction. It was considered that the enzyme and the substrate formed a transitional complex in the hydrolysis process. The transitional complex provided the buffering capacity pH 5. The results indicate of the hydrolyzate solution at around that industrialization of the enzymatic hydrolysis in a water medium is feasible.

Cellulose↗
PubMed2001

Asymmetric synthesis of (-)-eburnamonine and (+)-epi-eburnamonine from (4S)-4-ethyl-4-[2-(hydroxycarbonyl)ethyl]-2-butyrolactone.

The key chiral nonracemic 4,4-disubstituted 2-butyrolactone carboxylic acid, (S)-4, is readily accessible via an efficient and stereospecific dirhodium(II) tetraacetate catalyzed tertiary C-H insertion reaction of the diazomalonate (S)-5. The coupling of the acid (S)-4 with tryptamine produces the amide (S)-3, which is then transformed into the aldehyde 23 and hydroxy-lactam 24. Acid-mediated Pictet-Spengler cyclization of 23 and 24 produces the tetracyclic indole lactams (1S,12bS)-25a and (1S,12bR)-25b. Compounds 25a and 25b are converted, via the lactam alcohols 30a and 30b, to (-)-eburnamonine (1a) and (+)-epi-eburnamonine (1b).

4-Butyrolactone↗
PubMed2001

Methyl analogues of the experimental Alzheimer drug phenserine: synthesis and structure/activity relationships for acetyl- and butyrylcholinesterase inhibitory action.

With the goal of developing potential Alzheimer's pharmacotherapeutics, we have synthesized a series of novel analogues of the potent anticholinesterases phenserine (2) and physostigmine (1). These derivatives contain methyl (3, 4, 6), dimethyl (5, 7, 8, 10, 11) and trimethyl (14) substituents in each position of the phenyl group of the phenylcarbamoyl moieties, and with N-methyl and 6-methyl substituents (12, 13, 31, 33). We also quantified the inhibitory action of these compounds against human acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). An analysis of the structure/anticholinesterase activity relationship of the described compounds, together with molecular modeling, confirmed the catalytic triad mechanism of the binding of this class of carabamate analogues within AChE and BChE and defined structural requirements for their differential inhibition.

Acetylcholinesterase↗
PubMed2001

Expression of cyclins E1 and E2 during mouse development and in neoplasia.

Cyclin E1 (formerly called cyclin E) and the recently described cyclin E2 belong to the family of E-type cyclins that operate during the G(1)/S phase progression in mammalian cells. The two E-cyclins share a catalytic partner, cyclin-dependent kinase 2 (CDK2), and activate their associated kinase activities at similar times during cell cycle progression. Despite these similarities, it is unknown whether the two proteins perform distinct functions, or, alternatively, they control S-phase entry of different cell types in a tissue-specific fashion. To start addressing in vivo functions of E-cyclins, we determined the expression pattern of cyclins E1 and E2 during normal mouse development. We found that the two E-cyclins showed very similar patterns of expression; both were expressed within the proliferating compartment during embryo development. Analyses of cells and tissues lacking members of the retinoblastoma (pRB) family of proteins revealed that the expression of both cyclins is controlled in a pRB-dependent, but p107- and p130-independent fashion, likely through the pRB-dependent E2F transcription factors. We also found that cyclins E1 and E2 are expressed at high levels in mouse breast tumors driven by the Myc oncogene. Last, we found that cyclin E2 is overexpressed in approximately 24% of analyzed human mammary carcinomas. Collectively these findings suggest that the expression of cyclins E1 and E2 is governed by similar molecular circuitry.

Animals↗
PubMed2001

Antisense inhibition of Chk2/hCds1 expression attenuates DNA damage-induced S and G2 checkpoints and enhances apoptotic activity in HEK-293 cells.

The cellular response to DNA damage involves checkpoint controls that delay cell cycle progression in order to provide time for repair of damaged DNA. Chk2/hCds1 is a recently identified homolog of the yeast Cds1 kinase that is involved in cell cycle checkpoint response to DNA damage. To investigate the functions of Chk2/hCds1 in response to DNA damage in mammalian cells, we established a stable human kidney embryonic cell line (HEK-293) that expresses antisense Chk2/hCds1 (Chk2AS) under the control of an inducible promoter. Cells that express Chk2AS display defective S-phase delay in response to DNA replication-mediated DNA damage induced by the topoisomerase I inhibitor camptothecin. The defective G2 checkpoint was also observed in Chk2AS cells exposed to the DNA damaging agent VP-16 or gamma-radiation. Enhanced apoptosis was observed in Chk2AS cells after exposure to gamma-radiation or camptothecin. No p53 activation was observed after DNA damage in HEK-293 or Chk2AS cells. Our results indicate that perturbation of Chk2/hCds1 expression adversely affects the S- and G2-phase checkpoints following DNA damage or DNA replication block, and suggest that reduced expression of Chk2/hCds1 might promote a p53-independent apoptotic response.

Apoptosis↗
PubMed2001

Angiopoietin-1, unlike angiopoietin-2, is incorporated into the extracellular matrix via its linker peptide region.

Angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) affect angiogenesis differently during embryogenesis and tumorigenesis. In an attempt to understand the molecular basis underlying the distinct roles of those two homologous molecules, we investigated the association of Ang-1 and Ang-2 with the extracellular matrix (ECM). TA3 murine mammary carcinoma (TA3) and Lewis lung carcinoma cells expressing v5 epitope-tagged Ang-1 and Ang-2 were used in our studies. The results indicated that Ang-1 is secreted and incorporated into the ECM of the tumor cells, whereas Ang-2 is not associated with the ECM. The mutagenesis study indicated the domain that is responsible for the ECM association of Ang-1 is the linker peptide region between the coiled-coil and the fibrinogen-like domains. A weak binding between the coiled-coil domain of Ang-1 and the ECM was observed. Immunocytochemistry study revealed a distinct ECM distribution pattern of Ang-1, which is quite different from that of fibronectin, laminin, and collagen types I and IV. The ECM-associated Ang-1 proteins are released, and Tie-2 receptors are phosphorylated upon the adhesion of human umbilical vein endothelial cells. Implications of the difference in the ECM association of Ang-1 and Ang-2, which are related to the regulation of angiopoietin activity and their roles in local versus distant angiogenesis during tumor metastasis, are discussed.

Angiopoietin-1↗
PubMed2001

Specific protection against breast cancers by cyclin D1 ablation.

Breast cancer is the most common malignancy among women. Most of these cancers overexpress cyclin D1, a component of the core cell-cycle machinery. We previously generated mice lacking cyclin D1 using gene targeting. Here we report that these cyclin D1-deficient mice are resistant to breast cancers induced by the neu and ras oncogenes. However, animals lacking cyclin D1 remain fully sensitive to other oncogenic pathways of the mammary epithelium, such as those driven by c-myc or Wnt-1. Our analyses revealed that, in mammary epithelial cells, the Neu-Ras pathway is connected to the cell-cycle machinery by cyclin D1, explaining the absolute dependency on cyclin D1 for malignant transformation in this tissue. Our results suggest that an anti-cyclin D1 therapy might be highly specific in treating human breast cancers with activated Neu-Ras pathways.

Animals↗
PubMed2001

Direct evidence for a geometrically constrained "entatic state" effect on copper(II/I) electron-transfer kinetics as manifested in metastable intermediates.

The absolute magnitude of an "entatic" (constrained) state effect has never been quantitatively demonstrated. In the current study, we have examined the electron-transfer kinetics for five closely related copper(II/I) complexes formed with all possible diastereomers of [14]aneS(4) (1,4,8,11-tetrathiacyclotetradecane) in which both ethylene bridges have been replaced by cis- or trans-1,2-cyclohexane. The crystal structures of all five Cu(II) complexes and a representative Cu(I) complex have been established by X-ray diffraction. For each complex, the cross-reaction rate constants have been determined with six different oxidants and reductants in aqueous solution at 25 degrees C, mu = 0.10 M. The value of the electron self-exchange rate constant (k(11)) has then been calculated from each cross reaction rate constant using the Marcus cross relation. All five Cu(II/I) systems show evidence of a dual-pathway square scheme mechanism for which the two individual k(11) values have been evaluated. In combination with similar values previously determined for the parent complex, Cu(II/I)([14]aneS(4)), and corresponding complexes with the two related monocyclohexanediyl derivatives, we now have evaluated a total of 16 self-exchange rate constants which span nearly 6 orders of magnitude for these 8 closely related Cu(II/I) systems. Application of the stability constants for the formation of the corresponding 16 metastable intermediates--as previously determined by rapid-scan cyclic voltammetry--makes it possible to calculate the specific electron self-exchange rate constants representing the reaction of each of the strained intermediate species exchanging electrons with their stable redox partners--the first time that calculations of this type have been possible. All but three of these 16 specific self-exchange rate constants fall within--or very close to--the range of 10(5)-10(6) M(-1) s(-1), values which are characteristic of the most labile Cu(II/I) systems previously reported, including the blue copper proteins. The results of the current investigation provide the first unequivocal demonstration of the efficacy of the entatic state concept as applied to Cu(II/I) systems.

Copper↗
PubMed2001

Preliminary experiment of fluorescent X-ray computed tomography to detect dual agents for biological study.

The simultaneous observation of various information, such as blood flow, tissue metabolism and distribution of receptors, is quite important in order to understand the functional state of biomedical objects. The simultaneous detectability of contrast agents by fluorescent X-ray computed tomography (FXCT) with synchrotron radiation is examined in this study. The system consisted of a silicon (111) double-crystal monochromator, an X-ray slit system, a scanning table, a PIN diode, a highly purified germanium detector and an X-ray charge-coupled device (CCD) camera. The monochromatic X-ray beam energy was adjusted to 37.0 keV and collimated into a pencil beam of 1 x 1 mm. The fluorescent spectra of the K alpha lines for iodine and xenon were detected simultaneously. FXCT could image the distribution of both iodine and xenon agents in a phantom clearly and the contrast ratio was significantly better than that of transmission X-ray computed tomography images.

Fluorescence↗
PubMed2001

Tandem ligation of unprotected peptides through thiaprolyl and cysteinyl bonds in water.

Tandem ligation for the synthesis and modification of proteins entails forming two or more regiospecific amide bonds of multiple free peptide segments without a protecting-group scheme. We here describe a semi-orthogonal strategy for ligating three unprotected peptide segments, two of which contain N-terminal (NT) cysteine, to form in tandem two amide bonds, an Xaa-SPro (thiaproline), and then an Xaa-Cys. This strategy exploits the strong preference of an NT-cysteinyl peptide under acidic conditions to undergo selectively an SPro-imine ligation rather than a Cys-thioester ligation. Operationally, it was performed in the N --> C direction, first by an imine ligation at pH < 3 to afford an Xaa-thiazolidine ester bond between a peptide containing a carboxyl terminal (CT)-glycoaldehyde ester and a second peptide containing both an NT-Cys and a CT-thioester. The newly created O-ester-linked segment with a CT-thioester was then ligated to another NT-cysteinyl peptide through thioester ligation at pH > 7 to form an Xaa-Cys bond. Concurrently, this basic condition also catalyzed the O,N-acyl migration of an Xaa-thiazolidine ester to the Xaa-SPro bond at the first ligation site to complete the tandem three-segment ligation. Both ligation reactions were performed in aqueous buffered solvents. The effectiveness of this three-segment ligation strategy was tested in six peptides ranging from 19 to 70 amino acids, including thiaproline --> proline analogues of somatostatins and two CC-chemokines. The thiaproline replacements in these peptides and proteins did not result in altered biological activity. By eliminating the protecting-group scheme and coupling reagents, tandem ligation of multiple free peptide segments in aqueous solutions enhances the scope of protein synthesis and may provide a useful approach for combinatorial segment synthesis.

Amino Acid Sequence↗
PubMed2001

Tyrosine kinase-dependent, phosphatidylinositol 3'-kinase, and mitogen-activated protein kinase-independent signaling pathways prevent lung adenocarcinoma cells from anoikis.

Normal epithelial cells are anchorage-dependent. Detachment of normal epithelial cells from their substratum causes apoptosis, termed anoikis. Malignant tumor cells, however, can survive and proliferate independent of anchorage. To understand the molecular basis of tumor cell anchorage independence, we investigated the role of tyrosine kinases and their downstream signaling pathways in anoikis resistance of human lung adenocarcinoma cells. Four of the five lung adenocarcinoma cell lines analyzed are resistant to anoikis. Tyrosine kinase inhibitor genistein rendered three of them sensitive to anoikis. Although cell detachment induced rapid protein tyrosine dephosphorylation in Madin-Darby canine kidney cells, a nontransformed epithelial cell line, tyrosine phosphorylation of several proteins in the tumor cells is anchorage-independent. Similarly, phosphorylation of Akt and mitogen-activated protein kinase, two signaling proteins downstream of tyrosine kinases, was decreased in Madin-Darby canine kidney cells but increased in some of the tumor cells upon cell detachment. Inhibition of phosphorylation of the two proteins, however, did not induce anoikis in the tumor cells. Specific inhibitors to several known tyrosine kinases also failed to induce anoikis in these cells. These data suggest the existence of tyrosine kinase-dependent phosphatidylinositol 3'-kinase and mitogen-activated protein kinase-independent signaling pathways that function to regulate cell survival and death. Alteration in these pathways may count for the anchorage-independent survival of the lung adenocarcinoma cells and other malignant tumor cells.

Adenocarcinoma↗
PubMed2001

Retinal uptake of intravitreally injected Hsc/Hsp70 and its effect on susceptibility to light damage.

PURPOSE: To evaluate the uptake by the rat retina of an intravitreally injected mixture of the constitutive and inducible forms of the 70 kD heat shock protein (Hsc/Hsp70) and test its potential to protect photoreceptors from light damage. METHODS: Hsc/Hsp70 and actin (control protein) were labeled with fluorescein (referred to as fl-Hsc/Hsp70 and fl-actin). The labeled proteins were microinjected intravitreally into the normal or light damaged rat eye and each eye collected at three intervals after the injections. Retinal uptake of Hsc/Hsp70 or actin was studied in frozen sections using epifluorescence microscopy and in western blots of retinal homogenates using an anti-fluorescein antibody. Additionally, the cytoprotective effects of Hsc/Hsp70 were tested in rats that first were exposed to bright light (170 ft-c) for 24 h and then given an intravitreal injection of the protein immediately thereafter. Ten days later, photoreceptor damage was evaluated by measuring the area of the outer nuclear layer at fixed locations along the circumference of the retina. RESULTS: The fluorescein-labeled proteins were detected in the retina one h after administration and were retained there for more than 6 h. They were diffusely distributed, primarily in the nerve fiber layer, ganglion cell layer, and plexiform layers. Fl-Hsc/Hsp70 was also found in the outer nuclear layer (ONL) at 6 h after injection. At 24 h post-injection, the proteins were undetectable by epifluorescence microscopy of retinal sections, but could still be detected in western blots of retinal homogenates. The pattern of protein uptake was similar in light-damaged retinas. Ten days after light damage, the retinas in those eyes that received injections of Hsc/Hsp70 had greater ONL areas compared to either the light-damaged retinas of uninjected eyes or those that had received actin. The difference was statistically significant (p<0.05). CONCLUSIONS: Intravitreally injected Hsc/Hsp70 is taken up by retinal cells and, when administered after an acute injury like light damage, increased the number of surviving photoreceptors.

Animals↗
PubMed2001

Phenotypic correction of lipid storage and growth arrest in wolman disease fibroblasts by gene transfer of lysosomal acid lipase.

Wolman disease is a lethal lysosomal storage disease due to deficiency of lysosomal acid lipase (LAL). Wolman disease is characterized by pronounced hepatic involvement while neurological symptoms are uncommon, making Wolman disease an attractive candidate for liver-directed gene therapy. This study was performed to test the effects of gene replacement in fibroblasts lacking LAL, using a recombinant adenovirus encoding the human LAL cDNA (AdhLAL). Human fibroblasts from a Wolman disease patient were infected with AdhLAL and showed a dose-dependent increase in LAL protein and activity up to 5-fold above levels in control fibroblasts. Furthermore, 72 hr after infection with AdhLAL there was a dose-dependent correction of the severe lipid storage phenotype of Wolman disease fibroblasts. Electron microscopy confirmed significant correction of the lysosomal lipid storage in AdhLAL-infected Wolman disease fibroblasts at the ultrastructural level. Intravenous injection of AdhLAL into wild-type mice resulted in a 13.5-fold increase in hepatic LAL activity, and overexpression of LAL was not associated with toxic side effects. These data demonstrate high-level lysosomal expression of recombinant LAL in vitro and in vivo and show the feasibility of gene therapeutic strategies for the treatment of Wolman disease.

Adenoviridae↗
PubMed2001

Enantioselective syntheses of monotetrahydrofuran Annonaceous acetogenins tonkinecin and annonacin starting from carbohydrates.

The total synthesis of two mono-THF acetogenins, tonkinecin (1) and annonacin (2), is reported in full detail. Terminal acetylene 3 prepared from D-glucono-delta-lactone and asymmetric dihydroxylation was employed as a common intermediate for both targets 1 and 2. Pd(0)-catalyzed coupling reaction of 3 with vinyl iodides 4 and 5, the chiral centers of which were taken from D-xylose and S-(-)-ethyl lactate, afforded enyne 26 and 27, respectively. Selective hydrogenation of 26 or 27 with diimide followed by removal of MOM ethers completed the synthesis of 1. A coupling reaction between the lithium derivative of 3 and epoxide 6 in the presence of boron trifluoride etherate gave 42. Both chiral centers in epoxide 6 were taken from L-ascorbic acid. Subsequent catalytic hydrogenation and MOM protection led to 43b. Introduction of the butenolide moiety by aldol condensation of protected S-lactal followed by cleavage of all MOM ethers completed the synthesis of 2.

Carbohydrates↗
PubMed2001

Deletion of the p27Kip1 gene restores normal development in cyclin D1-deficient mice.

D-type cyclins (cyclins D1, D2, and D3) are key components of cell cycle machinery in mammalian cells. These proteins are believed to drive cell cycle progression by associating with their kinase partners, cyclin-dependent kinases, and by directing phosphorylation of critical cellular substrates. In addition, D-cyclins play a kinase-independent role by sequestering cell cycle inhibitors p27(Kip1) and p21(Cip1). In the past, we and others generated cyclin D1-deficient mice and have shown that these mice display developmental abnormalities, hypoplastic retinas, and pregnancy-insensitive mammary glands. To test the significance of cyclin D1-p27(Kip1) interaction within a living mouse, we crossed cyclin D1-deficient mice with mice lacking p27(Kip1), and we generated double-mutant cyclin D1(-/-)p27(-/-) animals. Here we report that ablation of p27(Kip1) restores essentially normal development in cyclin D1-deficient mice. Our results provide genetic evidence that p27(Kip1) functions downstream of cyclin D1.

Animals↗
PubMed2001

Correlates of functional disability in essential tremor.

The decision to treat patients with essential tremor (ET) is based primarily on the functional impact of the tremor. Correlates of functional disability, apart from the severity of the tremor itself, have not been studied. The objective of this work was to study correlates of functional disability in ET, and to present data on the extent of functional disability in community-dwelling ET cases. ET cases and age-matched control subjects were ascertained from a tertiary referral center at Columbia-Presbyterian Medical Center and a community in northern Manhattan, N.Y. Subjects underwent a 2.5-hour evaluation, including a tremor disability questionnaire, a videotaped tremor examination rated by a neurologist, a performance-based test of function, quantitative computerized tremor analysis, the Hamilton Anxiety Rating Scale, and the depression module of the Structured Clinical Interview for DSM-IV. Seventy-six (85.4%) of 89 cases reported disability on > or =1 item on the disability questionnaire. In multivariate linear regression analyses, current major depression, Hamilton Anxiety Rating Scale score, age, and tremor severity were independently correlated with performance-based test scores. Twenty-seven (73.0%) of 37 community cases reported disability on > or =1 (mean = 8.4) item on the questionnaire, and 25 (67.6%) demonstrated moderate or greater difficulty on > or =1 (mean = 4.2) task in a performance-based test. Depression, anxiety, and age, independent of the severity of tremor, were associated with greater functional disability in ET, so that these factors must be considered when assessing the impact of new treatments in ET. Among a group of community-dwelling cases, approximately three-quarters reported disability, suggesting that the number of individuals who might receive some benefit from advances in the treatment of ET is probably a great deal larger than previously thought.

Activities of Daily Living↗