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Biomedical subjects

L Tong

Publications and source records attributed to L Tong.

At least 109 records · Page 6Linked to original sources
PubMed1996

Lung carcinoma in former smokers.

BACKGROUND: A reduction in the risk of lung carcinoma and a lower death rate among former smokers (FS) compared with current smokers (CS) have been documented in numerous U.S. and international studies. The main objective of our study was to compare the differences in demographic and clinical characteristics in groups stratified by smoking status and gender to evaluate the effect of smoking history and cessation on age at lung carcinoma diagnosis and on specific histologic type. METHODS: We conducted a cross-sectional study of lung cancer at The University of Texas M.D. Anderson Cancer Center from January 1986 to December 1990 and from January 1992 to December 1993. This study included 1039 patients age 19-88 with confirmed primary lung carcinoma who responded to self-administered risk factor questionnaires. Among them, 497 patients (47.83%) were CS, 444 patients (42.73%) were FS, 98 patients (9.43%) had never smoked (NS), and 840 patients (80.8%) were heavy smokers (more than 20 pack-years). RESULTS: The median age at lung carcinoma diagnosis for FS was slightly later than that for CS. The histologic type of lung carcinoma for those who had quit smoking more than 20 years previously was not significantly different from that of NS, but was significantly different from that of CS (P < 0.05) and from those who quit smoking fewer than 10 years previously (P < 0.10). CS was a positive predictor for both small cell carcinoma (odds ratio [OR] = 8.79) and squamous cell carcinoma (OR = 2.11) and negatively associated with adenocarcinoma (OR = 0.50), whereas FS was a positive predictor only for small cell carcinoma (OR = 5.50). The variable of pack-years was negatively associated with adenocarcinoma and positively associated with small cell carcinoma in all patients combined and in women, and was also positively associated with squamous carcinoma in all patients after adjustment by smoking status. CONCLUSIONS: These results indicate that smoking cessation or less life-time smoking exposure affects the distribution of specific histologic subtypes of lung cancer, especially for women, and that smoking cessation may postpone the age at which lung cancer occurs.

Adenocarcinoma↗
PubMed1996

Effect of nerve growth factor on AP-1, NF-kappa B, and Oct DNA binding activity in apoptotic PC12 cells: extrinsic and intrinsic elements.

Both intrinsic signals, such as serum and neurotrophic factor deprivation, and extrinsic events or agents, such as oxidative stress and glucose deprivation, can induce cell death in pheochromocytoma (PC12) cells. Also, treatment with nerve growth factor (NGF) reduces cell death due to the treatments mentioned. Serumless-induced cell death, as a model of apoptosis, has been intensively investigated in PC12 cells. In the present study, we investigated the molecular components of H2O2-induced cell death and compared it with serumless-induced cell death. Exposure of PC12 cells to intermediate concentrations of H2O2 (100 microM) induced nuclear condensation and DNA fragmentation, indicating that there is an apoptotic component in H2O2-induced cell death. Since transcription factors have been shown to play an essential role in the control of cellular proliferation, differentiation, and survival, we measured changes in the DNA binding activities of the transcription factors activator protein-1 (AP-1), nuclear factor kappa B (NF-kappa B), and octamer-binding protein (Oct) by electrophoretic mobility shift assay (EMSA) after H2O2 treatment and serum deprivation, both in the absence and presence of exogenous NGF in PC12 cells. AP-1 DNA binding activity transiently increased during apoptosis due to serum deprivation, and NGF treatment further stimulated AP-1 DNA binding activity in a more persistent fashion. NF-kappa B DNA binding activity only increased slightly after serum deprivation, and NGF treatment of PC12 cells decreased NF-kappa B binding activity in the late stages of serum deprivation. Oct DNA binding activity decreased after serum deprivation, while NGF had an opposite effect. AP-1 DNA binding activity also transiently increased after H2O2 treatment, as did NF-kappa B DNA binding activity. Our results suggest that AP-1 is likely to be a common component of signaling pathways associated with both the induction or suppression of apoptosis induced by intrinsic or extrinsic stimuli.

Animals↗
PubMed1996

Crystal structures of the human p56lck SH2 domain in complex with two short phosphotyrosyl peptides at 1.0 A and 1.8 A resolution.

src homology 2 (SH2) domains are modules of about 100 amino acid residues and bind to phosphotyrosine-containing motifs in a sequence-specific manner. They play important roles in intracellular signal transduction and represent potential targets for pharmacological intervention. The protein tyrosine kinase p56lck is a member of the src family and is involved in T-cell activation. The crystal structure of its SH2 domain with an 11-residue peptide showed that the phosphotyrosine and the Ile residue at the pY + 3 position are recognized by the SH2 domain. We present here the crystal structure of the SH2 domain of human p56lck in complex with the short phosphotyrosyl peptide Ac-pTyr-Glu-Glu-Ile (pYEEI peptide) at 1.0 A resolution. The structural analysis at atomic resolution reveals that residue Arg134 (alphaA2), which interacts with the phosphotyrosine side-chain, is present in two conformations in the complex. The structure at 1.8 A resolution of the complex with the phosphotyrosyl peptide Ac-pTyr-Glu-Glu-Gly (pYEEG peptide), which is 11 fold less potent, shows another binding mode for the pY + 3 residue as well as rearrangements of the side-chain of Arg196 (EF3) and one of the water molecules at the base of the pY + 3 pocket. The structure of the complex with the short pYEEI peptide at atomic resolution represents a good starting point for the design and optimization of new inhibitors. Comparative structural analysis of many different inhibitor complexes will be an important component of this drug discovery process.

Amino Acid Sequence↗
PubMed1996

Structure solution of a cubic crystal of concanavalin A complexed with methyl alpha-D-glucopyranoside.

The solution of the cubic crystal form (a = 167.8 A) of concanavalin A complexed with the monosaccharide methyl alpha-D-glucopyranoside is described. The space group has been determined as I2(1)3 rather than I23. The use of cadmium to replace cobalt at the transition metal-ion binding site and to replace calcium at its binding site proved to be crucial to the successful solution of the crystal structure. The relatively small isomorphous signals of 21 e(-) for the replacement of cobalt and 28 e(-) for the replacement of calcium, yielded interpretable difference Patterson maps. The electron-density map calculated in space group I2(1)3 at 5.4 A resolution, based on phases derived from single- and double-substituted cadmium differences, revealed a classical concanavalin A tetramer of 222 point symmetry, as seen in all the known crystal structures of concanavalin A. Rigid-body refinement at 3.6 A using the refined coordinates of saccharide-free concanavalin A converged to an R factor of 27.4%. A molecular-replacement analysis, consistent with this crystal structure, and initial experiences in the incorrect space group I23 are described as these also prove to be instructive.

Journal Article↗
PubMed1996

Crystal structure of dimeric HIV-1 capsid protein.

X-ray diffraction analysis of a human immunodeficiency virus (HIV-1) capsid (CA) protein shows that each monomer within the dimer consists of seven alpha-helices, five of which are arranged in a coiled coil-like structure. Sequence assignments were made for two of the helices, and tentative connectivity of the remainder of the protein was confirmed by the recent solution structure of a monomeric N-terminal fragment. The C-terminal third of the protein is mostly disordered in the crystal. The longest helices in the coiled coil-like structure are separated by a long, highly antigenic peptide that includes the binding site of an antibody fragment complexed with CA in the crystal. The site of binding of the Fab, the position of the antigenic loop and the site of cleavage between the matrix protein and CA establish the side of the dimer that would be on the exterior of the retroviral core.

Amino Acid Sequence↗
PubMed1996

Zinc absorption and intestinal losses of endogenous zinc in young Chinese women with marginal zinc intakes.

The objective of this study was to determine fractional absorption of exogenous zinc and intestinal excretion of endogenous zinc in women of childbearing age whose habitual dietary zinc intake was marginal. The target population (L group) comprised residents of a remote farming village in northeast China and the control subjects (M group) were residents of Beijing. Mean (+/-SE) calculated dietary zinc intakes were 5.2 +/- 0.2 and 8.1 +/- 0.2 mg/d, respectively. The phytate-zinc molar ratio in the diet of both groups was approximately 10:1. 70Zn was administered intravenously before breakfast and 67Zn orally with three main meals in 1 d. Subsequently, all feces were collected quantitatively until the second visible marker had been excreted and 12-h urine samples were collected on days 3-9. Fractional absorption was determined by measuring cumulative fecal excretion of nonabsorbed 67Zn and endogenous fecal zinc by isotope-dilution technique (70Zn). Fractional absorption values for L and M groups, respectively, were 0.31 +/- 0.03 and 0.34 +/- 0.03 (P=0.45). Corresponding figures for endogenous fecal zinc were 1.30 +/- 0.07 and 2.34 +/- 0.20 mg Zn/d (P<0.001). Both the estimated total size of the pools of zinc that exchange with zinc in plasma within 2 d (r=0.762, P<0.001) and the excretion of endogenous zinc in the feces (r=0.706, P<0.0001) were positively correlated with calculated total daily zinc absorption. We conclude that fractional absorption of zinc does not differ between women consuming marginal and adequate quantities of zinc in their diets, but endogenous zinc is conserved effectively by the intestine in women whose habitual dietary zinc is marginal.

Absorption↗
PubMed1996

Several polyhydroxymonoamide renin inhibitors assume similar conformations in the unbound and renin-bound states.

The solution conformations of three polyhydroxymonoamide renin inhibitors which differ in the relative configuration and position of the hydroxyl groups at the P3 position were investigated by NMR spectroscopy. The NMR data are consistent with a predominant conformation in DMSO with the exception that two inhibitors exhibit conformational averaging about a torsion angle along P3. Comparisons with the renin-bound structures determined by X-ray crystallography [Tong et al., (1995) J. Mol. Biol. 250, 211] show that the unbound and renin-bound conformations are similar (with exceptions in the P3 position). This similarity suggests that gross conformational changes of the inhibitor are not a prerequisite for binding to renin. Apart from being able to tolerate different dihydroxylated structures at P3, renin can also accommodate different conformations at P3. Differences were observed at the P3 position between the inhibitors in the unbound state, between the unbound and renin-bound states, and between the renin-bound states.

Alcohols↗
PubMed1996

[Cholesterol granulomatous tympano-mastoiditis].

In order to investigate the early diagnosis and proper management of the cholesterol granulomatous tympanomastoiditis, 6 cases verified by pathology and surgery were reviewed. All of these cases had a longterm or a historical otitis media. Among them, different clinical features were presented, such as chronic serous otitis media, idiopathic blue eardrum, or as a primary occupying lesion of the middle ear. Depend on the extension of the disease, surgical procedure varied in the 6 cases, including exploratory tympanotomy, ventilation tube insertion, antroatticotomy, simple mastoidectomy, and radical mastoidectomy. Postoperative follow up for at least one--7 year showed no recurrence, and hearing improvement in 5 cases. The clinical basis of the diagnosis and management of this disease were also discussed.

Adolescent↗
PubMed1995

Crystallographic studies on the binding modes of P2-P3 butanediamide renin inhibitors.

The binding modes of three peptidomimetic P2-P3 butanediamide renin inhibitors have been determined by x-ray crystallography. The inhibitors are bound with their backbones in an extended conformation, and their side chains occupying the S5 to S1' pockets. A (2-amino-4-thiazolyl)methyl side chain at the P2 position shows stronger hydrogen-bonding and van der Waals interactions with renin than the His side chain, which is present in the natural substrate. The ACHPA-gamma-lactam transition state analog has similar interactions with renin as the dihydroxyethylene transition state analog.

Crystallography↗
PubMed1995

Novel non-nucleoside inhibitors of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase. 4. 2-Substituted dipyridodiazepinones as potent inhibitors of both wild-type and cysteine-181 HIV-1 reverse transcriptase enzymes.

The major cause of viral resistance to the potent human immunodeficiency virus type 1 reverse transcriptase (RT) inhibitor nevirapine is the mutation substituting cysteine for tyrosine-181 in RT (Y181C RT). An evaluation, against Y181C RT, of previously described analogs of nevirapine revealed that the 2-chlorodipyridodiazepinone 16 is an effective inhibitor of this mutant enzyme. The detailed examination of the structure-activity relationship of 2-substituted dipyridodiazepinones presented below shows that combined activity against the wild-type and Y181C enzymes is achieved with aryl substituents at the 2-position of the tricyclic ring system. In addition, the substitution pattern at C-4, N-5, and N-11 of the dipyridodiazepinone ring system optimum for inhibition of both wild-type and Y181C RT is no longer the 4-methyl-11-cyclopropyl substitution preferred against the wild-type enzyme but rather the 5-methyl-11-ethyl (or 11-cyclopropyl) pattern. The more potent 2-substituted dipyridodiazepinones were evaluated against mutant RT enzymes (L100I RT, K103N RT, P236L RT, and E138K RT) that confer resistance to other non-nucleoside RT inhibitors, and compounds 42, 62, and 67, with pyrrolyl, aminophenyl, and aminopyridyl substituents, respectively, at the 2-position, were found to be effective inhibitors of these mutant enzymes also.

Cell Line↗
PubMed1995

Structure determination of coxsackievirus B3 to 3.5 A resolution.

The crystal structure of coxsackievirus B3 (CVB3) has been determined to 3.5 A resolution. The icosahedral CVB3 particles crystallize in the monoclinic space group, P2(1), (a = 574.6, b = 302.1, c = 521.6 A, beta = 107.7 degrees ) with two virions in the asymmetric unit giving 120-fold non-crystallographic redundancy. The crystals diffracted to 2.7 A resolution and the X-ray data set was 55% complete to 3.0,4, resolution. Systematically weak reflections and the self-rotation function established pseudo R32 symmetry with each particle sitting on a 32 special position. This constrained the orientation and position of each particle in the monoclinic cell to near face-centered positions and allowed for a total of six possible monoclinic space-group settings. Correct interpretation of the high-resolution (3.0-3.2 A) self-rotation function was instrumental in determining the deviations from R32 orientations of the virus particles in the unit cell. Accurate particle orientations permitted the correct assignment of the crystal space-group setting amongst the six ambiguous possibilities and for the correct determination of particle positions. Real-space electron-density averaging and phase refinement, using human rhinovius 14 (HRV14) as an initial phasing model, have been carried out to 3.5 A resolution. The initial structural model has been built and refined to 3.5 A resolution using X-PLOR.

Journal Article↗
PubMed1995

Phase refinement and extension by means of non-crystallographic symmetry averaging using parallel computers.

Electron-density averaging, fast Fourier synthesis and fast Fourier analysis programs have been adapted for parallel-computing systems. These have been linked to perform iterative phase improvement and extension utilizing non-crystallographic symmetry and solvent flattening. Various strategies for parallel algorithms have been tested on a variety of computers as a function of the number of computer nodes. Some experimental timing results are discussed.

Journal Article↗
PubMed1995

High resolution crystal structures of recombinant human renin in complex with polyhydroxymonoamide inhibitors.

The crystal structures of recombinant glycosylated human renin in complex with several polyhydroxymonoamide inhibitors have been determined at up to 1.8 A resolution. The high resolution structures permit a detailed analysis of the conformation of renin, the interactions between the inhibitors and renin, and the network of ordered water molecules. The polyhydroxymonoamide inhibitors are bound with their backbones in an extended conformation, and with their side-chains occupying the S3 to S1 pockets. The inhibited renin molecules are shown to exist in both the closed and the open conformations. Inhibitors bound to the two distinct forms of renin can assume different conformations at the P3 position.

Amides↗
PubMed1995

Transcription factor DNA binding activity in PC12 cells undergoing apoptosis after glucose deprivation.

Following hypoglycemic injury to rat pheochromocytoma PC12 cells, cells display nuclear chromatin condensation and nucleosome-sized DNA fragmentation. Electrophoretic mobility shift assays were used to characterize binding of nuclear proteins to consensus sequences for AP-1, nuclear factor kappa B (NF kappa B), and octamer family after glucose deprivation. While AP-1 DNA binding activity and NF kappa B DNA binding activity were transiently stimulated, DNA binding to the octamer motif decreased. These data suggest that changes in nuclear protein binding to specific consensus sequences are an early molecular event in hypoglycemic-ischemic injury-induced neuronal cell death.

Animals↗
PubMed1995

Reciprocal-space molecular-replacement averaging.

The molecular-replacement equations, in which electron-density averaging and skew averaging have been unified, were used in reciprocal space to refine and extend the resolution of phased reflections. A procedure has been developed for the treatment of molecular envelopes of general shape. The equations were successfully applied to the reflection data of bacteriophage phiX174 (60-fold redundancy). Truncation of the G diffraction function beyond the first few nodes did not have a significant effect on the quality of the molecular-replacement equations. Reciprocal-space molecular-replacement averaging should prove to be a useful alternative to real-space averaging. Strategies are discussed that are possible only in reciprocal space.

Journal Article↗
PubMed1995

Crystal structures of HIV-2 protease in complex with inhibitors containing the hydroxyethylamine dipeptide isostere.

BACKGROUND: The HIV protease is essential for the life cycle of the virus and is an important target for the development of therapeutic treatments against AIDS. The structures of HIV protease in complex with different inhibitors have helped in understanding the interactions between inhibitors and the protease and in the design and optimization of HIV protease inhibitors. RESULTS: We report here crystal structures at up to 1.7 A resolution of the homodimeric HIV-2 protease in complex with seven inhibitors containing the hydroxyethylamine dipeptide isostere. A novel dimethylphenoxyacetyl group that is present in some of these inhibitors is inserted between residues 48' and 49' in the flap of the protease and residues 29' and 30' (where a prime indicates a residue in the second monomer), which undergo a conformational change to accommodate the phenyl ring of the inhibitor. CONCLUSIONS: This study shows that besides the residues in the flap and residues 79-81 in the S1 substrate-binding pocket which undergo conformational changes upon inhibitor binding, residues 29 and 30 can also adapt their conformation to fit certain inhibitors. Conformational flexibility of the HIV protease plays an important role in inhibitor binding.

Acquired Immunodeficiency Syndrome↗
PubMed1995

[A survey on HIV and HV infection of heroin addicts in Linchang and Kunming].

Serum samples were collected from 353 heroin addicts in Linchang Prefecture and Kunming Area, Yunnan Province for detecting anti-HIV with ELISA and Western Blot, and 319 of them also for detecting various infection markers of hepatitis A, B, C and D with ELISA. Results showed no anti-HIV was found among them, overall infection prevalence rate of hepatitis A, B, C and D was 78.11%, 72.73% for males and 90.91% for females, and 1.57%, 63.97%, 51.85% and 5.79% positive rates for anti-HAV-IgM, HBV markers, anti-HCV and HDAg and/or anti-HD-IgM, respectively. Prevalence of mixed infection with different types of hepatitis was 40.07%, and 35.35% for mixed HBV and HCV. Infection rate of hepatitis B and C in Kunming Area was significantly higher than that in Linchang Prefecture, and so did in Han nationality than in other minority nationalities. It suggests hepatitis viruses infection is caused by drug abuse, use of non-sterilizing syringes with others.

Adolescent↗