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Biomedical subjects

B L Chen

Publications and source records attributed to B L Chen.

At least 19 recordsLinked to original sources
PubMed2001

[Telomerase activity in bladder cancer tissues].

OBJECTIVE: To study the correlation between telomerase and bladder cancer. METHODS: The telomerase activity was detected by telomerase PCR ELISA in 41 cases of bladder cancer tissues and 23 cases of non-cancerous bladder tissues. RESULTS: The telomerase activity was positive in 34 cases of bladder cancer tissues (82.9%) and 1 case of non-cancerous tissues (4.3%); the difference of positive rate was significant (P < 0.01). CONCLUSIONS: Telomerase activity is related with bladder cancer closely; telomerase activation may be an important molecular step in the initiation and development of bladder cancer; telomerase may be an excellent molecular biomarker in finding bladder cancer at an early stage and in postoperative following-up.

Adult↗
PubMed2001

[Prolactin in normal pregnancy and severe pregnancy-induced hypertension].

OBJECTIVE: This study was to investigate the relationship between serum prolactin and pregnancy-induced hypertension. METHOD: Maternal serum prolactin was estimated by radioimmunoassay in 89 normal pregnant women and 52 patients with severe pregnancy-induced hypertension at 28 to 42 week gestation. RESULTS: In normal pregnancy, prolactin level increased progressively from a mean value of 270 mg.L-1 in the 24th week to 440 mg.L-1 in the 34th week and decreased progressively from the 38th week to the 40th week. In severe pregnancy-induced hypertension increased progressively too; 31 of 52 patients with severe prolactin showed high prolactin levels in zone A (> mean value + standard of prolactin values in the normal pregnancy), 10 patients in zone B (mean + standard to mean) and 11 patients in zone C (< mean). CONCLUSION: These results suggest that high prolactin levels may play an important role in the pathogenesis of severe pregnancy-induced hypertension.

Adult↗
PubMed2001

Partition of polycyclic aromatic hydrocarbons on organobentonites from water.

A series of organobentonites synthesized by exchanging organic cation such as dodecyltri-methylammonium (DTMA), benzyldimethyltetradecylammonium (BDTDA), cetyltrimethyl-ammonium (CTMA), octodeyltrimethylammonium (OTMA) on bentonite. The optimal condition, properties and mechanisms for the organobentonites to sorb phenanthrene, anthracene, naphthalene, acenaphthene in water were investigated in detail. The partition behavior was determined for four polycyclic aromatic hydrocarbons (PAHs), such as naphthalene, phenanthrene, anthracene and acenaphthene, from water to a series of organobentonites. The interlayer spacings and organic carbon contents of organobentonites, removal rate and sorption capacities for organobentonites to treat phenanthrene, anthracene, naphthalene, acenaphthene were correlated to the length of alkyl chains and the amounts of cation surfactant exchanged on the bentonite. Phenanthrene, anthracene, naphthalene, and acenaphthene sorption to organobentonites were characterized by linear isotherms, indicating solute partition between water and the organic phase composed of the large alkyl functional groups of quaternary ammonium cations. PAHs distribution coefficients (Kd) between organobentonites and water were proportional to the organic carbon contents of organobentonites. However, the partition coefficients (Koc) were nearly constants for PAHs in the system of organobentonite-water. The Koc of phenanthrene, anthracene, naphthalene, acenaphthene were 2.621 x 10(5), 2.106 x 10(5), 2.247 x 10(4), 5.085 x 10(4), respectively. The means Koc values on the organobentonites are about ten to twenty times larger than the values on the soils/sediments, what is significant prerequisite for organobentonite to apply to remediation of pollution soil and groundwater. The sorption mechanism was also evaluated from octanol-water partition coefficients and aqueous solubility of PAHs. The correlations between 1gKoc and 1gKow, 1gKoc and 1gS for PAHs in the system of water/organobenotonites are also discussed.

Adsorption↗
PubMed2000

[Expression of different receptors of the apoptosis inducing gene TRAIL in human ovarian tumors].

Reverse transcriptase polymerase chain reaction (RT-PCR) was applied to assay mRNA expression of TRAIl(the TNF related apoptosis inducing ligand) receptors (DR5, DcR1, and DcR2) in 3 cases of normal ovarian tissues, 6 cases of ovarian benign tumors, and 16 cases of ovarian cancers. Peripheral blood lymphocytes were used as a positive control. Positive expression of the DR5 and DcR1 were found in peripheral blood lymphocytes and 3 cases of normal ovaries. Positive expressions of the DR5 and DcR1 were 83.3%(5/6) in benign ovarian tumors and 68.8%(11/16) in ovarian cancers respectively. Positive expression of the DcR2 was only found in normal ovaries and benign tumors. These findings suggest that expression of different receptors may play an important role in the apoptosis regulation of ovarian tumors, especially DcR2.

Apoptosis↗
PubMed1999

Solubility of recombinant human tissue factor pathway inhibitor.

Study of recombinant human tissue factor pathway inhibitor (rhTFPI) solubility shows (1) an inverted bell-shaped pH-solubility profile with a broad solubility minimum between pH 5 and 10 such that the solubility minimum midpoint is 2-3 pH units away from its isoelectric point; (2) a negative temperature-solubility coefficient; (3) a strong dependence of solubility on the valence of electrolytes, with both multivalent cations and anions enhancing this effect; and (4) a significant increase of solubility in the presence of charged polymers. At pH 6-7, rhTFPI solubility-salt profiles display typical salting-in and salting-out biphasic effects. At a slightly lower pH (pH 5), a third phase in addition to the salting-in and salting-out phases was observed at low ionic strength conditions (5 to 50 mM) where rhTFPI solubility increased as salt concentration decreased. The salting-out constant for rhTFPI in NaCl is 1.04 M(-1) and is independent of the pH of the solution. Resolubilization of rhTFPI precipitates revealed that "insolubility precipitates" (seen during buffer exchanges) resulted from protein solute saturation and could be redissolved by "native" solvent conditions. On the other hand, "instability precipitates" (typically seen after exposure to elevated temperatures or extended storage periods) were caused by insoluble protein aggregate formation and required strongly denaturing conditions to redissolve.

Amino Acid Sequence↗
PubMed1999

Flutamide suppressed prostate hypertrophy in rats and mice.

AIM: To study the suppressive effect of flutamide (Flu) on benign prostate hypertrophy. METHODS: The effect of Flu 10, 25, and 50 mg.kg-1 i.g. on the prostate was tested in orchiectomized rats with s.c. testosterone daily for 30 d and in mice implanted with homologous strain fetal mouse urogenital sinus for 14 d. RESULTS: 1) Flu dose-dependently suppressed the weight and volume of each lobe of the prostate to about 10%-50% of control. Also, the acini and height of epithelial cells atrophied. The effect was more powerful than that of estradiol (Est). 2) The weight and volume of the mouse prostate diminished in Flu-treated groups, but the dose-response relationship was seen only in volume. In this model, Est was better than Flu. CONCLUSION: Flu possesses the suppressive action on benign prostate hypertrophy.

Androgen Antagonists↗
PubMed1998

Correlation between the 1.6 A crystal structure and mutational analysis of keratinocyte growth factor.

A comprehensive deletion, mutational, and structural analysis of the native recombinant keratinocyte growth factor (KGF) polypeptide has resulted in the identification of the amino acids responsible for its biological activity. One of these KGF mutants (delta23KGF-R144Q) has biological activity comparable to the native protein, and its crystal structure was determined by the multiple isomorphous replacement plus anomalous scattering method (MIRAS). The structure of KGF reveals that it folds into a beta-trefoil motif similar to other members of fibroblast growth factor (FGF) family whose structures have been resolved. This fold consists of 12 anti-parallel beta-strands in which three pairs of the strands form a six-stranded beta-barrel structure and the other three pairs of beta-strands cap the barrel with hairpin triplets forming a triangular array. KGF has 10 well-defined beta strands, which form five double-stranded anti-parallel beta-sheets. A sixth poorly defined beta-strand pair is in the loop between residues 133 and 144, and is defined by only a single hydrogen bond between the two strands. The KGF mutant has 10 additional ordered amino terminus residues (24-33) compared to the other FGF structures, which are important for biological activity. Based on mutagenesis, thermal stability, and structural data we postulate that residues TRP125, THR126, and His127 predominantly confer receptor binding specificity to KGF. Additionally, residues GLN152, GLN138, and THR42 are implicated in heparin binding. The increased thermal stability of delta23KGF-R144Q can structurally be explained by the additional formation of hydrogen bonds between the GLN side chain and a main-chain carbonyl on an adjoining loop. The correlation of the structure and biochemistry of KGF provides a framework for a rational design of this potentially important human therapeutic.

Amino Acid Sequence↗
PubMed1997

Stromal fibroblasts influence oral squamous-cell carcinoma cell interactions with tenascin-C.

In this study we identified tenascin-C (TN-C) and one of its integrin receptors, alpha(v)beta6, in oral squamous-cell carcinoma (SCC) specimens. Neither TN-C nor alpha(v)beta6 are expressed in normal oral mucosa. We also studied 2 human oral squamous-cell carcinoma cell lines: the highly invasive HSC-3 cells, and the poorly invasive SCC-25 cells. We determined that adhesion of these cells to TN-C involves both alpha2 and alpha(v) integrins. Migration on TN-C by oral SCC cells required fibroblast-conditioned medium and did not occur in its absence. This migration was blocked by anti-alpha2 and anti-alpha(v) antibodies and was partially inhibited by antibodies to hepatocyte growth factor, epidermal growth factor and transforming growth factor-beta1. When seeded on TN-C, the poorly invasive SCC-25 cells formed alpha(v)beta6-positive focal contacts; the HSC-3 cells did not. HSC-3, SCC-25 and PTF cells secrete TN-C into the culture medium, as determined by Western blot. However, when HSC-3 cells were inoculated into the floor of the mouth of nude mice, only murine TN-C could be identified in the reactive stroma adjacent to the resulting tumor nests, demonstrating that in vivo, HSC-3 cells do not secrete TN-C. Our results demonstrate that alpha(v)beta6 and tenascin-C are neo-expressed in oral squamous-cell carcinoma, and that the tumor stromal environment is influential in oral SCC behavior.

Animals↗
PubMed1996

Stabilization of recombinant human keratinocyte growth factor by osmolytes and salts.

Keratinocyte growth factor (KGF) has limited stability in aqueous media, as it undergoes denaturation followed by aggregation at 37 degrees C. Heparin and anionic polymers have been shown to increase the denaturation temperatures and extend the half-life of the monomeric, native form of KGF during storage. These polymers, however, bind more than one protein molecule with high affinity, and such tight complex formation may cause problems for clinical use. In this study, we have tested low molecular weight additives, such as osmolytes and salts, for their effects on the stability of KGF against thermal denaturation and high-temperature storage. Salts such as NaCl, sodium phosphate, ammonium sulfate, and sodium citrate were highly effective in increasing both the denaturation temperature and storage stability. The fact that the same additives stabilize KGF against both stresses is consistent with the idea that the storage stability is determined by denaturation followed by aggregation. Among the osmolytes tested, N,N'-dimethylglycine, trehalose, and sucrose were also effective stabilizers. However, quantitative comparison of the osmolytes tested indicated that their effectiveness on the thermal denaturation and the storage stability is not exactly parallel, suggesting that other factors also contribute to the storage stability.

Drug Stability↗
PubMed1994

Strategies to suppress aggregation of recombinant keratinocyte growth factor during liquid formulation development.

Recombinant human keratinocyte growth factor (rhKGF) is a fairly unstable protein, posing a challenging problem for long-term storage. During storage, the protein unfolds at relatively low temperatures and the unfolded proteins aggregate rapidly, leading to the formation of large visible precipitates. Thermal unfolding of rhKGF displays a similar pattern, i.e., unfolding is followed immediately by aggregation as the temperature is increased. As the unfolding and aggregation (precipitation) of rhKGF limit the storage life of the protein, a search for stabilizers to suppress rhKGF unfolding and aggregation has been done by examining the effects of excipients on thermal melting temperature and on the rate of protein aggregation during storage. Sulfated polysaccharides and citrate are found to be effective in increasing the melting temperature of rhKGF or preventing its aggregation. In particular, 0.5% (w/v) heparin and high molecular weight dextran sulfate, and 0.5 M citrate are highly effective, decreasing the rates of rhKGF aggregation by about 50-fold. Other negatively charged small ions, such as phosphate, also have moderate stabilizing effects on rhKGF. A mechanistic study of the aggregation pathway of rhKGF has led to a better understanding of the stabilizing effects of these molecules. Molecules which enhance rhKGF conformational stability are capable of effectively suppressing rhKGF aggregation.

Animals↗
PubMed1994

Aggregation pathway of recombinant human keratinocyte growth factor and its stabilization.

Recombinant human keratinocyte growth factor (rhKGF) is prone to aggregation at elevated temperatures. Its aggregation pathway is proposed to proceed initially with a conformational change which perhaps results from repulsion between positively charged residues in clusters forming heparin binding sites. Unfolding of the protein leads to formation of large soluble aggregates. These soluble aggregates then form disulfide cross-linked precipitates. Finally these precipitates are converted to scrambled disulfides and/or non-disulfide cross-linked precipitates. Stabilizers such as heparin, sulfated polysaccharides, anionic polymers and citrate can greatly decrease the rate of aggregation of rhKGF at elevated temperatures. These molecules may all act by reducing charge repulsion on the protein thus stabilizing the native conformation. EDTA, on the other hand, is found to inhibit disulfide formation in aggregates and has only a moderate stabilizing effect on rhKGF.

Anions↗
PubMed1994

[Distal free-end removable partial denture fabrication in reduced interarch distance patients].

Reduced interarch distance, resulted from extrusion of antagonist teeth and/or down growth of alveolar bone due to long-time absence of natural teeth without adequate restoration in this area, is found in many cases. In such condition, it is difficult to fabricate a distal free-end removable partial denture with conventional resin base because of insufficient space for denture base resin, metal framework and artificial teeth, and the long-term prognosis of the denture is questionable due to minimized strength of the denture base. In this article, the authors demonstrate the clinical and laboratory methods and procedures for distal extension removable partial denture construction in reduced interach distance condition. Partial metal base in the insufficient vertical space area of the ordinary denture base is altered, the metal occlusal scheme and buccal resin facing are designed, instead of resin denture teeth. These designs provide strength, esthetic and masticatory function to the denture, and the denture base is convenient for future denture repair or relining.

Denture Bases↗
PubMed1992

Folding kinetics of T4 lysozyme and nine mutants at 12 degrees C.

The kinetics of unfolding and refolding of T4 lysozyme and nine of its mutants have been investigated as a function of guanidinium chloride concentration at 12 degrees C. All show simple two-state, first-order kinetics. Two types of mutants were studied: proline-alanine interchanges and substitutions at position 3 with side chains of varying hydrophobicity. Crystal structures are available for seven of the ten proteins. The effect of mutations on the folding kinetics is more pronounced and complex than on equilibrium thermodynamics. The proteins fall into two broad kinetic classes with one class rather close to the wild type. P86A is a mutant with marked changes in kinetics but only a very small change in stability. Since the 86 position is in the middle of an alpha-helix, the indications are that the helix containing an A residue is more stable in the transition state than one containing a P residue. The other mutants are more complicated, with the refolding and unfolding rates unequally affected by the mutations. On the basis of comparisons with other investigations, we conclude that the rate-determining step in the presence of guanidinium chloride is not the same as in aqueous solution and that it most likely precedes it. The indications are that we are studying the formation of a transition intermediate which is destabilized by the denaturant and which resembles the A intermediate of the framework or molten globule models for protein folding.

Amino Acid Sequence↗
PubMed1992

Lack of interaction between cefpirome and alcohol.

An observer-blind randomized, placebo-controlled, crossover study was conducted in 22 healthy male subjects. They received 2 g cefpirome or placebo intravenously following an overnight fast. One hour later they consumed a single 0.5 g/kg dose of alcohol. The treatments were reversed after a seven-day 'washout' period. Subjects were evaluated for any adverse events or 'disulfiram-like' symptoms. The effects of cefpirome on the pharmacokinetics of alcohol were also studied. There were no statistically significant differences in mean values for the various pharmacokinetic parameters for plasma alcohol between the cefpirome and placebo treatment groups. There were no side effects or 'disulfiram-like' reactions following consumption of alcohol in either group. A single iv dose of 2 g cefpirome was well-tolerated in healthy males and, moreover, pre-treatment with cefpirome did not adversely affect the metabolism of alcohol in these subjects.

Adult↗
PubMed1990

Synthesis of cyclic peptide homologs of glutathione as potential antitumor agents.

Two cyclic tripeptide homologs, cyclo(Glu[Cys-beta-Ala-]-OH) 8a, and cyclo(Glu[Cys-Gaba-]-OH) 8b, were synthesized by the pentafluorophenyl ester method in solution. These cyclic peptides are cyclo homologs of glutathione and are designed as potential antitumor agents. The 1H- and 13C-n.m.r. spectral parameters of cyclo(Glu[Cys(Bzl)-beta-Ala-]-OH) 7a were measured in DMSO-d6 and a possible conformation has been proposed. The cyclic peptide 8a showed low cytotoxic activities against three human tumor cell lines: KB, HeLa, and Colo 205.

Antineoplastic Agents↗
PubMed1989

Low-temperature unfolding of a mutant of phage T4 lysozyme. 1. Equilibrium studies.

The mutant protein I3C-C97/C54T of phage T4 lysozyme is free of sulfhydryl groups and has a genetically engineered disulfide bridge between positions 3 and 97 (Perry & Wetzel, 1986). This protein has a maximum stability at 12 degrees C in 3 M guanidinium chloride and undergoes reversible high- and low-temperature melting at 28 and -3 degrees C, respectively, in this medium. The free energy of stabilization of the protein has been studied over a range of temperature that includes both melting transitions. The stability curve fits a constant delta Cp model over the entire range, permitting an unusually complete determination of the thermodynamic parameters of the protein and demonstrating that the low-temperature unfolded form of the protein may be interpreted as an extrapolation with constant delta Cp of the high-temperature unfolded form. The free energy of unfolding is a linear function of guanidinium concentration within experimental error which permits a rough estimate of the stability of the protein at low temperatures and of the differential interaction of the unfolded protein with guanidinium chloride. These equilibrium studies provide a basis for the interpretation of the kinetic studies reported in the following paper.

Calorimetry↗