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Biomedical subjects

M Liu

Publications and source records attributed to M Liu.

At least 361 records · Page 20Linked to original sources
PubMed1999

[Ultra trace determination of platinum, palladium, gold and rhodium in minerals].

Our work studied the minerals dissolved in aqua regia. The trace Pt(II), Pd(II) Au (III) and Rh(I) complexes were loaded by the mixed carbon powder which carried diphenyl thiourea when aqua regia or hydrochloric acid media as well as stannous chloride were present. We added some carbon powder in ashen loader and determined the elements with atomic emission spectrometry. The determination sensitivity counted with 10 grams of samples is 1 x 10(-9). The RSD for 0.05 x 10(-6) standard Pt, Pd, Au and Rh solutions are 6.0%, 5.1%, 8.5% and 11.4%, respectively. The method is simple and operation is easy. The results satisfy our requirement.

English Abstract↗
PubMed1999

[Study on the interaction of copper-zinc superoxide dismutase with cobalt (II)-histidine by spectral analysis--II. Effect of amount of external added Co(His)n, phosphate].

The effect of changing the amount of external added Co(His)n and phosphate on the interaction of Cu2Zn2SOD with organic metal compound (Cobalt (II)-Histidine) have been studied by means of ICP, VIS and measurement of enzyme activity. It has found that in aqueous solution, there exists a direct interaction of the metal ions of the active center in the metalloenzyme (Cu2Zn2SOD) with external added Co(His)n. As a result, part of the metal ions in metalloenzyme were replaced and the corresponding metalloenzyme derivatives (Co (II)-substituted derivatives of SOD) were produced and the catalytic activity of enzyme were affected. It has also studied the intensity of interactions in different molar ratios (Cobalt (II)-Histidine) and of the presence of phosphate and got some results under the effect of corresponding factors.

Cobalt↗
PubMed1999

[Study on the interaction of copper-zinc superoxide dismutase with cobalt (II)-histidine by spectral analysis. II. Effects of pH, interaction time].

The direct interaction of Cu2Zn2SOD with organic metal compound (Cobalt (II)-Histidine) was studied by ICP, VIS and the measurement of enzyme activity, and also investigated the effect of pH values and different interaction times for this interaction. The results showed that with the increased in pH values and the more longer interaction times, the intensity of interaction were increased and the corresponding catalytic activity of enzyme were affected.

Cobalt↗
PubMed1998

Molecular cloning and expression of human grap-2, a novel leukocyte-specific SH2- and SH3-containing adaptor-like protein that binds to gab-1.

The SH2- and SH3-containing adaptor molecules serve to recruit cytosolic signal-transducing molecules to the activated receptor tyrosine kinases. In this study, we report the molecular cloning of a novel adaptor-like protein, Grap-2 (Grb-2 related adaptor protein 2), using the multisubstrate docking protein Gab-1 as bait in the yeast two-hybrid system. Sequence analysis revealed that Grap-2 contains a SH3-SH2-SH3 structure that has a high degree of sequence homology to those of the Grb-2 and Grap adaptor molecules. However, unlike in Grap and Grb-2, the SH2 and the C-terminal SH3 domains of Grap-2 are separated by a 120-amino-acid glutamine-rich sequence that shows no apparent homology to any known molecule or structural motif. The C-terminal SH3 domain of Grap-2 alone is sufficient to bind to Gab-1. Furthermore, Northern blot analysis demonstrated that Grap-2 has two major transcripts of 1.4 and 4.0 kb that can only be detected in tissues rich in leukocytes and in two leukemia cell lines. This highly restricted pattern of expression suggests that Grap-2 may participate in leukocyte-specific protein tyrosine kinase signaling.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Preparation, Characterization, and Catalytic Properties of Polymer-Stabilized Ruthenium Colloids.

Poly(N-vinyl-2-pyrrolidone) (PVP)-stabilized ruthenium colloids were prepared by NaBH4 reduction at room temperature and characterized by transmission electron microscopy and x-ray photoelectron spectra. The average diameters of the colloids were 1.3-1.8 nm with final sigma = 0.4-0.7 nm with respect to the preparation conditions. The PVP-stabilized ruthenium colloids were used as catalysts in the hydrogenations of cyclooctene and n-heptene and the selective hydrogenation of citronellal to citronellol. Copyright 1998 Academic Press.

Journal Article↗
PubMed1998

Expression, characterization, and detection of human uridine phosphorylase and identification of variant uridine phosphorolytic activity in selected human tumors.

Uridine phosphorylase (UPase) catalyzes the reversible phosphorolysis of uridine to uracil. We purified the enzyme from the murine colon 26 tumor using a two-step procedure through 5-amino-benzylacyclouridine affinity chromatography. Antibodies raised in rabbits against the purified protein revealed single bands in Western blots of normal human tissue and tumor extracts. The polyclonal antibody used to screen a human liver expression library allowed the isolation of a 1.2-kb clone that contained the entire open reading frame of the human UPase. The UPase cDNA has been expressed as a fusion protein in Escherichia coli using the pMal-C2 vector. The kinetic analysis demonstrated that the recombinant UPase preferentially uses uridine, 5-fluorouracil, and uracil as substrates, although lower levels of activity were observed with 2-deoxyuridine and thymidine. Clinical samples of human tumors and adjacent normal tissues were assayed for phosphorolytic activity and sensitivity to 5-benzylacyclouridine (BAU), a potent inhibitor of the enzyme presently in Phase I-II clinical trial. Activity in normal tissues appeared to be low but very sensitive to BAU (approximately 90% inhibition at 10 microM). Tumors had generally 2-3-fold greater activity compared with adjacent normal tissues. In breast cancer specimens and head-neck squamous carcinomas, however, uridine cleavage was only partially inhibited (40-60%) by 10 or 100 microM BAU. The BAU-insensitive activity requires phosphate and pH conditions similar to the normal enzyme, and the new phosphorolytic activity was independent from thymidine phosphorylase. The BAU-insensitive phosphorolytic activity in selected tumors, coupled with the potent inhibitory activity of BAU against the "classical" uridine phosphorylase in normal human tissues, provides the rationale for combining BAU with 5-fluorouracil in the treatment of breast and head-neck tumors.

Amino Acid Sequence↗
PubMed1998

Antitumor activity of SCH 66336, an orally bioavailable tricyclic inhibitor of farnesyl protein transferase, in human tumor xenograft models and wap-ras transgenic mice.

We have been developing a series of nonpeptidic, small molecule farnesyl protein transferase inhibitors that share a common tricyclic nucleus and compete with peptide/protein substrates for binding to farnesyl protein transferase. Here, we report on pharmacological and in vivo studies with SCH 66336, a lead compound in this structural class. SCH 66336 potently inhibits Ha-Ras processing in whole cells and blocks the transformed growth properties of fibroblasts and human tumor cell lines expressing activated Ki-Ras proteins. The anchorage-independent growth of many human tumor lines that lack an activated ras oncogene is also blocked by treatment with SCH 66336. In mouse, rat, and monkey systems, SCH 66336 has excellent oral bioavailability and pharmacokinetic properties. In the nude mouse, SCH 66336 demonstrated potent oral activity in a wide array of human tumor xenograft models including tumors of colon, lung, pancreas, prostate, and urinary bladder origin. Enhanced in vivo efficacy was observed when SCH 66336 was combined with various cytotoxic agents (cyclophosphamide, 5-fluorouracil, and vincristine). In a Ha-Ras transgenic mouse model, prophylactic treatment with SCH 66336 delayed tumor onset, reduced the average number of tumors/mouse, and reduced the average tumor weight/animal. In a therapeutic mode in which gavage treatment was initiated after the transgenic mice had developed palpable tumors, significant tumor regression was induced by SCH 66336 in a dose-dependent fashion. This was associated with increased apoptosis and decreased DNA synthesis in tumors of animals treated with SCH 66336. Enhanced efficacy was also observed in this model when SCH 66336 was combined with cyclophosphamide. SCH 66336 is presently being evaluated in Phase I clinical trials.

3T3 Cells↗
PubMed1998

A human RNA polymerase II transcription termination factor is a SWI2/SNF2 family member.

We obtained protein sequence information from Drosophila factor 2, an ATP-dependent RNA polymerase II transcription termination factor, and discovered that it was identical to a SWI2/SNF2 family member called lodestar. Portions of putative human and Caenorhabditis elegans homologues were found in the sequence data bases and a complete cDNA for the human factor was generated using polymerase chain reaction techniques. Recombinant human factor 2 was produced in a baculovirus expression system, purified, and characterized. Similar to the authentic Drosophila factor, the human factor displayed a strong double-stranded DNA-dependent ATPase activity that was inhibited by single-stranded DNA and exhibited RNA polymerase II termination activity. Both factors were able to work on elongation complexes from either species. We discuss the mechanism of termination by factor 2 and the implications for the role of factor 2 in cellular activities.

Adenosine Triphosphatases↗
PubMed1998

Modulation of the positional specificity of lecithin-cholesterol acyltransferase by the acyl group composition of its phosphatidylcholine substrate: role of the sn-1-acyl group.

Human lecithin-cholesterol acyltransferase (LCAT), which is normally specific for the sn-2 position of phosphatidylcholine (PC), derives a significant percentage of acyl groups from the sn-1 position, when sn-2 is occupied by 18:0, 20:4, or 22:6. We investigated the relative importance of the two acyl groups of PC in determining the positional specificity by first analyzing the cholesteryl esters formed in the presence of symmetric PCs labeled at sn-2. Both human and rat LCATs transferred exclusively the sn-2-acyl group from all symmetric PCs, including 18:0-18:0, and 20:4-20:4, showing that the presence of these fatty acids at sn-2 does not automatically alter the positional specificity. The role of the sn-1-acyl group was then tested by using PCs containing 20:4 or 18:0 at sn-2 and fatty acids of various chain lengths and unsaturation at sn-1. With 20:4 at sn-2 and saturated fatty acids of various chain lengths at sn-1, human and rat LCATs derived, respectively, 5-72% and 1-20% of the total acyl groups from the sn-1 position. However, the chain length of the sn-1-acyl did not correlate with its utilization by either enzyme. Various unsaturated fatty acids at sn-1 also were transferred by human LCAT at a higher rate (5-75% of total) than they were transferred by rat LCAT (0-21%). With sn-2-18:0 PCs, however, rat LCAT exhibited greater alteration in positional specificity (30-95% from sn-1) than human LCAT (15-83% from sn-1). These results show that while the primary determinant of positional specificity is the sn-2-acyl group of PC, the structure of sn-1-acyl significantly modifies it.

Acylation↗
PubMed1998

Effect of complement inhibition with soluble complement receptor 1 on pig allotransplant lung function.

BACKGROUND: Lung dysfunction after transplantation continues to be a significant clinical problem. Soluble complement receptor 1 (sCR1) is a potent inhibitor of complement activation. We evaluated the inhibitory effect of sCR1 on complement activation and reperfusion injury in pig lung allografts. METHODS: In a randomized and blinded study, left lung transplantation was performed in 13 pigs. Donor lungs were flushed and then stored for 30 hr at 4 degrees C. Control pigs (n=7) received saline, and the treatment group (n=6) received 15 mg/kg sCR1 1 hr before reperfusion. One hour after reperfusion, the right pulmonary artery was clamped for 10 min to assess the function of the transplanted lung. Pulmonary function was assessed again on day 3. RESULTS: Complement inhibition was 93% in the sCR1 group and returned to baseline (8% inhibition) after 3 days. There was a trend toward a higher partial pressure of oxygen at 1 hr in the sCR1 group compared with the control group (mean +/- SE: 408+/-42 mmHg vs. 288+/-69 mmHg, P = 0.19). Alveolar ventilation was better in the sCR1 group than in the control group (P = 0.01) at 1 hr. Mixed venous saturation was significantly lower in the control group at both 1 hr (P = 0.02) and 3 days (P = 0.001). The wet/dry weight of the lung tissue was lower in the sCR1 group compared with the control group on day 3 (P < 0.05). Chemiluminescence, an index of phagocyte priming, was lower in the sCR1 group when cells were stimulated with complement opsonized zymosan but not when stimulated with zymosan or phorbol myristate acetate. CONCLUSION: sCR1 improves ventilation, reduces pulmonary edema, and may be beneficial in improving posttransplant lung oxygenation.

Animals↗
PubMed1998

Transition metals bind to glycated proteins forming redox active "glycochelates": implications for the pathogenesis of certain diabetic complications.

The present investigations arose from our interest in the possibility that some structures which arise secondary to protein glycation might bind transition metals such as iron and copper. In support of this we find that, when glycated, three different proteins--albumin, gelatin (a soluble collagen fragment) and elastin--all gain a substantial affinity for the transition metals iron and copper. The glycated proteins bind at least three times as much iron as do the non-glycated proteins. Similarly, glycated albumin and gelatin also bind 2-3 times as much copper. Furthermore, at least in the case of copper bound to glycated albumin, the bound metal retains redox activity and participates in the catalytic oxidation of ascorbic acid. Should similar "glycochelates" form in vivo in diabetics, reactions mediated by these chelates may be involved in certain complications of diabetes.

Albumins↗
PubMed1998

The observation of the local ordering characteristics of spermidine-condensed DNA: atomic force microscopy and polarizing microscopy studies.

Condensation of DNA by multivalent cations can provide useful insights into the physical factors governing the folding and packaging of DNA in vivo. In this work, local ordered structures of spermidine-DNA complexes prepared from different DNA concentrations have been examined by using atomic force microscopy (AFM) and polarizing microscopy (PM). Two types (I and II) of DNA condensates, significantly different in sizes, were observed. It was found that for extremely dilute solutions (DNA concentrations around 1 ng/microl or below), the DNA molecules would collapse into toroidal structures with a volume equivalent to a single lambda-DNA (type I). In relatively dilute solutions (DNA concentrations between 1 and 10 ng/microll), a significantly larger structure of multimolecular toroids (circular and elliptical, type II) were formed, which were constructed by many fine particles. Measurements show that the average diameter of these fine particles was similar to the outer diameter of the monomolecular toroids observed in extremely dilute solutions, and the thickness of the multimolecular toroids had a distribution of multi-layers with height increments of 11 nm, indicating that the multimolecular toroidal structures have lamellar characteristics. Moreover, by enriching the DNA-spermidine complexes in very diluted solution, branch-like structures constructed by subunits were observed by using AFM. The analysis of the pellets in polarizing microscopy reveals a liquid-crystal-like pattern. These observations suggest that DNA-spermidine condensation could have multiple stages, which are very sensitive to the DNA and spermidine concentrations.

Bacteriophage lambda↗
PubMed1998

Potent, selective, and orally bioavailable tricyclic pyridyl acetamide N-oxide inhibitors of farnesyl protein transferase with enhanced in vivo antitumor activity.

We previously reported compound 1 as a potent farnesyl protein transferase (FPT) inhibitor that exhibited reasonable pharmacokinetic stability and showed moderate in vivo activity against a variety of tumor cell lines. The analogous C-11 single compound, pyridylacetamide 2, was found to be more potent than 1 in FPT inhibition. Further studies showed that modification of the ethano bridge of the tricyclic ring system by conversion into a double bond with concomitant introduction of a single bond at C-11 piperidine resulted in compound 3 that had superior FPT activity and pharmacokinetic stability. Compound 4, a 5-bromo-substituted analogue of 3, showed improved FPT activity, had good cellular activity, and demonstrated a remarkably improved pharmacokinetic profile with AUC of 84.9 and t1/2 of 82 min. Compound4 inhibited the growth of solid tumor in DLD-1 model by 70% at 50 mpk and 52% at 10 mpk.

Administration, Oral↗
PubMed1998

Antioxidant action via p53-mediated apoptosis.

The biological effects of antioxidants are often considered in terms of their effects on oxygen or lipid radicals. However, antioxidants can also exert their effects through altering the cellular redox potential. Herein, we report that sulfur-containing antioxidants such as N-acetylcysteine and dimercaptopropanol induced apoptosis in several transformed cell lines and transformed primary cultures but not in normal cells. In contrast, chain-breaking antioxidants such as vitamin E lacked this activity. An increased glutathione level was not required for apoptosis; however, all apoptosis-inducing antioxidants elevated the total cellular thiol levels. Antioxidant-induced apoptosis required the p53 tumor suppressor gene. N-Acetylcysteine elevated p53 expression posttranscriptionally by increasing the rate of p53 mRNA translation rather than by altering the protein stability. The p53 induction occurred in normal cells. These observations indicate a redox sensor for p53 induction in vivo, with additional transformation-specific information being required for apoptosis. Manipulating p53-dependent apoptosis with nontoxic antioxidants may have a direct clinical application.

Acetylcysteine↗
PubMed1998

Inhibitors of farnesyl protein transferase. 4-Amido, 4-carbamoyl, and 4-carboxamido derivatives of 1-(8-chloro-6,11-dihydro-5H-benzo[5,6]- cyclohepta[1,2-b]pyridin-11-yl)piperazine and 1-(3-bromo-8-chloro-6,11- dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)piperazine.

The synthesis of a variety of novel 4-amido, 4-carbamoyl and 4-carboxamido derivatives of 1-(8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl) piperazine to explore the SAR of this series of FPT inhibitors is described. This resulted in the synthesis of the 4- and 3-pyridylacetyl analogues 45a and 50a, respectively, both of which were orally active but were found to be rapidly metabolized in vivo. Identification of the principal metabolites led to the synthesis of a variety of new compounds that would be less readily metabolized, the most interesting of which were the 3- and 4-pyridylacetyl N-oxides 80a and 83a. Novel replacements for the pyridylacetyl moiety were also sought, and this resulted in the discovery of the 4-N-methyl and 4-N-carboxamidopiperidinylacetyl derivatives 135a and 160a, respectively. All of these derivatives exhibited greatly improved pharmacokinetics. The synthesis of the corresponding 3-bromo analogues resulted in the discovery of the 4-pyridylacetyl N-oxides 83b (+/-) and 85b [11S(-)] and the 4-carboxamidopiperidinylacetamido derivative 160b (+/-), all of which exhibited potent FPT inhibition in vitro. All three showed excellent oral bioavailability in vivo in nude mice and cynomolgus monkeys and exhibited excellent antitumor efficacy against a series of tumor cell lines when dosed orally in nude mice.

3T3 Cells↗
PubMed1998

Adenovirus-mediated interleukin-10 gene transfer inhibits post-transplant fibrous airway obliteration in an animal model of bronchiolitis obliterans.

Bronchiolitis obliterans, a form of chronic allograft rejection characterized by progressive fibrous obliteration of the airways, is the major obstacle limiting prolonged survival of lung transplant recipients. To date, no effective therapy against this fatal complication exists. Interleukin-10 (IL-10), an anti-inflammatory and immunosuppressive cytokine, inhibits various T cell and antigen-presenting cell functions. We examined the effect of IL-10 in an animal model for bronchiolitis obliterans. A heterotopic tracheal transplant model was used. IL-10 was administered to the recipient either in its recombinant form by osmotic minipump or by adenoviral-mediated IL-10 gene transfer (Ad5E1mIL-10). Successful gene transfection and expression was confirmed by measuring circulating IL-10 protein. Tracheal allografts were assessed histologically based on a scoring system. IL-10 administration (in recombinant form or by gene transfer) inhibited the development of fibrous airway obliteration 3 weeks after transplantation in comparison to untreated controls (p < 0.05). This was demonstrated only if the delivery was initiated 5 days after transplantation and not if it was started at the time of transplantation. A single administration of the gene construct was sufficient to achieve the desired effect. We have shown that IL-10 can prevent the development of airway fibro-obliteration in this model. Gene transfection at a site distant from a graft can be used to produce a desired effect on the graft. IL-10 may be of major importance in the control of post-transplant bronchiolitis obliterans. The timing of its administration is critical and further studies are required to determine the mechanisms underlying the observed effects of IL-10.

Adenoviruses, Human↗
PubMed1998

Microwave a-Dipole Transitions of CH2DOH and CHD2OH in Excited Torsional States.

Previously identified, measured, and rotationally assigned but unpublished J = 0-1 and 1-2 microwave a-dipole lines for excited states of the torsion for CH2DOH and CHD2OH are given torsional assignments for the first four excited states. The troublesome assignments were for the K-1 = 0 lines of the o2 state of CH2DOH and the e2 state of CHD2OH, where a resonance is found for the J0J levels. The assignment for these states was facilitated by combination differences with the b- or c-dipole intratorsional state transitions, relative intensities, and FIR combination differences for the e2 and e3 states of CH2DOH. A few new b- and c-dipole assignments are reported for o2 of CH2DOH and e2 of CHD2OH. Transitions for these two states have been analyzed to estimate the strength of the resonant interaction and energy difference for the levels involved and to estimate how well the theory is predicting the K-1-dependent torsional energy levels. The empirically determined DeltaB and DeltaC from nonrigidity for each species for the four excited states should prove helpful for future calculations of vibration-internal rotation-overall rotation interactions in these molecules. Copyright 1998 Academic Press.

Journal Article↗