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Biomedical subjects

B Liu

Publications and source records attributed to B Liu.

At least 559 records · Page 31Linked to original sources
PubMed1995

Etoposide protein binding in cancer patients.

The protein binding of etoposide was studied in vivo in 36 cancer patients receiving etoposide therapy. Free etoposide was separated from plasma using an ultrafiltration method and the etoposide concentrations (free and total) were measured by high-performance liquid chromatography (HPLC). Considerable interpatient variation in the protein binding of etoposide was observed. The protein binding of etoposide varied from 80% to 97% (mean, 93%). Univariate analysis showed a significant inverse correlation between the free fraction of etoposide and serum albumin (r = 0.74), daily dose (r = 0.37) and age (r = -0.34). Multivariate analysis demonstrated that serum albumin and age were independent predictors of the etoposide free fraction. Serum bilirubin showed no correlation with etoposide protein binding. There is wide variation in etoposide protein binding in cancer patients, which is mostly dependent on serum albumin concentration.

Administration, Oral↗
PubMed1995

A conserved sequence motif at the 5' terminus of the Southampton virus genome is characteristic of the Caliciviridae.

We have determined the 5'terminal cDNA sequence for the genome of Southampton virus, a recently characterized, human, small round-structured virus (SRSV). Genomic RNA was extracted directly from a stool sample and amplified by RT-PCR by homopolymer tailing of the 3' terminus of the cDNA. The additional sequence increases the overall length of the Southampton virus genome by 12 nucleotides, resulting in a significant change to the genome organization by extending the first large open reading frame (ORF) by 51 amino acids. The 5'terminal bases pGpT and the presence of conserved genome and putative subgenomic RNA terminal motifs are now prominent features shared between the human SRSV Southampton virus and the animal caliciviruses rabbit hemorrhagic disease virus and feline calicivirus.

Amino Acid Sequence↗
PubMed1995

Extracorporeal development and ultrarapid freezing of human fetal ova.

PURPOSE: The present study was performed to culture human fetal ova to determine whether they can be matured and cryopreserved using ultrarapid freezing. METHODS: Thirty-three pairs of fetal ovaries were obtained from fetuses of 16-20 weeks' gestation following elective abortion. Ovarian tissues were minced into approximately 1-mm sizes and cultured in Waymouth media either before or after ultrarapid freezing. The Waymouth medium was supplemented with 15% (v/v) fetal bovine serum, 0.03 IU/ml FSH and 35 ng/ml insulin. The tissue was cultured at 37 degrees C in 5% CO2 in air for 5-25 days in Falcon dishes and 30-40 days in Costar Transwell-COL membranes prior to induction of final maturation in the presence of LH and human follicular fluid. Minced tissues were also frozen by ultrarapid freezing in M199 with 4.2 M dimethylsulfoxide (DMSO) and 0.35 M sucrose and plunged directly into liquid nitrogen. For thawing, the straws were plunged into a 37 degrees C water bath for 5 s. The contents were then expelled and diluted 1:5 with thawing medium containing 0.42 M sucrose. After washing the thawed tissues were cultured as described for the fresh tissues. RESULTS: Patches of monolayer consisting of fibroblasts had formed within 2-3 days of culture of fresh tissues. After 1 week of culture, follicles separated out from the ovarian tissue but remained attached to the monolayer. The maximal number of follicles separating out from the tissue appeared about 1 week after initiating the culture (154 follicles per 10 fields at Day 5 and 61 and Day 25). After 40 days of culture in Costar dishes, 34% of the ova reached a diameter of more than 80 microns, which was significantly higher than at the beginning of culture (6%; P < 0.05). Among these ova, 34% were found to be surrounded by the zona pellucida, which was not observed at the beginning of culture. Following induction of final maturation, extrusion of the first polar body was noted in 25% of ova grown in Costar dishes for 40 days. Twelve percent of the oocytes showed the first polar body when they were grown in Costar dishes for less than 30 days. For frozen-thawed tissues, 14% of minced ovarian tissues displayed central necrosis immediately after thawing. Following digestion and Trypan blue staining, 75% of ova and 85% of somatic cells survived ultrapid freezing. Nineteen percent of the ova which have been cultured as described for fresh tissues displayed extrusion of the first polar body, comparing favorably with the 25% maturation rate observed with the fresh tissue (P > 0.05). CONCLUSION: This study demonstrates that morphologically normal, mature human ova can be obtained from primordial follicles in vitro development. Using a simple, quick ultrarapid freezing method, human fetal ova can be cryopreserved in the form of minced tissue without significantly compromising their ability to grow in vitro.

Animals↗
PubMed1995

Half-dose aprotinin preserves hemostatic function in patients undergoing bypass operations.

High-dose aprotinin reduces bleeding in cardiac operations but with potential side-effects and increased cost. It is therefore mandatory that the effectiveness of a low dose be investigated. Half of the Hammersmith regimen was studied in cardiac surgical patients to find out how it could reduce bleeding. Blood fibrinolysis parameters were studied in 40 elective patients undergoing coronary artery bypass grafting in a double-blind, placebo-controlled study design. The plasma activities of tissue plasminogen activator, plasminogen activator inhibitor, alpha 2-antiplasmin, plasminogen, fibrinogen, and D-dimer as well as platelet number, bleeding times, activated clotting time, and aprotinin plasma concentrations were assessed before, during, and after the operation. Fibrinolysis was inhibited by aprotinin as evidenced by decreased D-dimer (p = 0.0001) and tissue plasminogen activator (p = 0.0432) levels and increased plasminogen activator inhibitor (p = 0.0105) and alpha 2-antiplasmin (p = 0.0002) levels during the operation. A postoperative abnormal bleeding time occurred 38% more frequently in the placebo group (p < 0.05). Aprotinin plasma concentrations reached adequate levels to inhibit plasmin and plasma kallikrein. This study showed that half-dose aprotinin significantly inhibits fibrinolysis and prevents postoperative abnormal bleeding time in cardiac surgical patients.

Aged↗
PubMed1995

Topochemistry for preparing ligands that dimerize receptors.

BACKGROUND: The cyclic, disulfide-containing peptide, cyclo-Ac-[Cys-His-Pro-Gln-Gly-Pro-Pro-Cys]-NH2, binds to streptavidin with high affinity. In streptavidin-peptide cocrystals of space group I222, cyclic peptide monomers are bound on adjacent streptavidin tetramers related by a crystallographic two-fold symmetry axis. We set out to determine whether the disulfide bonds of the peptide, presented close to one another in the crystal, could undergo disulfide interchange to form a dimer. RESULTS: When juxtaposed, the disulfides of neighboring peptides undergo disulfide interchange, breaking and forming covalent disulfide bonds, to produce a peptide dimer adopting the symmetry of the crystal. This is the first example of a chemical transformation mediated by a protein crystal lattice. The structure of the streptavidin-bound monomer, and that of the dimer that was eventually produced from it in the crystal, were both determined from the same single crystal studied at different times. The two-fold symmetric peptide dimer was independently synthesized and shown to form crystals of dimerized streptavidin. CONCLUSIONS: We have shown that formation of a covalently linked peptide dimer can be mediated by a protein crystal lattice. The dimer thus produced dimerizes its target, streptavidin, suggesting that solid-state (or topochemical) reactions of this kind may be broadly useful for the preparation of ligands that can dimerize other protein targets.

Chromatography, High Pressure Liquid↗
PubMed1995

Mismatch repair gene defects in sporadic colorectal cancers with microsatellite instability.

Microsatellite instability has been observed in both sporadic and hereditary forms of colorectal cancer. In the hereditary form, this instability is generally due to germline mutations in mismatch repair (MMR) genes. However, only one in ten patients with sporadic tumours exhibiting microsatellite instability had a detectable germline mutation. Moreover, only three of seven sporadic tumour cell lines with microsatellite instability had mutations in a MMR gene, and these mutations could occur somatically. These results demonstrate that tumours can acquire somatic mutations that presumably do not directly affect cell growth but result only in genetic instability. They also suggest that many sporadic tumours with microsatellite instability have alterations in genes other than the four now known to participate in MMR.

Adult↗
PubMed1995

MSH2 deficient mice are viable and susceptible to lymphoid tumours.

Alterations of the human MSH2 gene, a homologue of the bacterial MutS mismatch repair gene, co-segregate with the majority of hereditary non-polyposis colon cancer (HNPCC) cases. We have generated homozygous MSH2-/- mice. Surprisingly, these mice were found to be viable, produced offspring in a mendelian ratio and bred through at least two generations. Starting at two months of age homozygous-/- mice began, with high frequency, to develop lymphoid tumours that contained microsatellite instabilities. These data establish a direct link between MSH2 deficiency and the pathogenesis of cancer. These mutant mice should be good models to study the progression of tumours and also to screen carcinogenic and anti-cancer agents.

Animals↗
PubMed1995

Genetic instability occurs in the majority of young patients with colorectal cancer.

Replication errors (RER) associated with genetic instability have been found in cancers of several different types and particularly in the tumours of patients with hereditary non-polyposis colorectal cancer (HNPCC). We have here determined the prevalence of such instability in relation to age among patients without HNPCC. Colorectal cancers (CRCs) in the majority of patients 35 years of age or younger exhibited instability (58% of 31 patients), whereas CRCs from patients older than 35 uncommonly did (12% of 158, p < 0.0001). Twelve of the patients under 35 with instability were evaluated for alterations of mismatch repair genes, and five were found to harbour germline mutations. These data suggest that the mechanisms underlying tumour development in young CRC patients differ from those in most older patients, regardless of HNPCC status. The results have important implications for genetic testing and management of young CRC patients and their families.

Adult↗
PubMed1995

Structural basis of drug resistance for the V82A mutant of HIV-1 proteinase.

A major problem in the development of antiviral therapies for AIDS has been the emergence of drug resistance. We report an analysis of the structure of a Val 82 to Ala mutant of HIV-1 proteinase complexed to A-77003, a C2 symmetry-based inhibitor. Modelling studies predicted that the V82A mutation would result in decreased van der Waals' interactions with the phenyl rings of A-77003 in both S1 and S1' subsites. Unexpected rearrangements of the protein backbone, however, resulted in favourable re-packing of inhibitor and enzyme atoms in the S1 but not the S1' subsite. This analysis reveals the importance of enzyme flexibility in accommodating alternate packing arrangements, and can be applied to the re-design of inhibitors targeted to drug resistant variants which emerge in the clinic.

Antiviral Agents↗
PubMed1995

Nucleotide sequence and expression of the genes for the alpha and beta subunits of phycocyanin in Cyanidium caldarium.

The nucleotide sequence of the plastid-encoded operon containing genes for the alpha (cpcA) and beta (cpcB) subunits of phycocyanin in the unicellular red alga Cyanidium caldarium is described. cpcB is located 5' to cpcA and the two genes are separated by a 102-bp spacer region. The transcription start site of cpcBA was mapped to 80 bp upstream of the ATG initiation codon of cpcB. Promoter-like elements similar to the -10 (TATAAT) and -35 (TTGACA) consensus promoters in bacteria were found 6 and 31 bp upstream of the transcription initiation site. Northern blotting revealed an abundant 1.3-kb cpcBA transcript in illuminated cells, but this transcript was undetectable in dark-grown cells. Expression levels of cpcBA in cells incubated with 10(-6) M heme in the dark were similar to those in cells illuminated for 24 h. Cells illuminated with 150 microM gabaculine (an inhibitor of delta-aminolevulinate synthesis) or 10 mM levulinic acid (an inhibitor of delta-aminolevulinate dehydrase) lacked detectable cpcBA transcripts. In cells illuminated with 200 microM N-methyl-mesoporphyrin IX (an inhibitor of ferrocheletase), inhibition of cpcBA expression and phycocyanin synthesis was similar. These results provide strong evidence that light induction of the cpcBA operon is dependent on synthesis of heme.

Amino Acid Sequence↗
PubMed1995

Normalized average glandular dose in magnification mammography.

PURPOSE: To evaluate the normalized average glandular dose (the average glandular dose per unit entrance skin exposure) in magnification mammography. MATERIALS AND METHODS: Photon transport in the breast was simulated by using Monte Carlo methods. A semielliptical cylinder containing glandular and adipose tissue was used to simulate the breast. Measured mammography spectra for a molybdenum target-molybdenum filter unit were utilized. The normalized average glandular dose was calculated as a function of half-value layer, tube voltage, breast thickness, and breast composition for typical magnification geometries. RESULTS: The normalized average glandular dose in magnification mammography is 7%-25% lower than that with the contact (nonmagnification) technique because of the effects of partial irradiation, smaller field size, and greater percentage depth dose gradient at the reduced source-to-skin distance. CONCLUSION: The normalized average glandular dose in magnification mammography is lower than that in contact mammography. The average glandular dose in magnification mammography, however, is still substantially greater due to the two to three times greater entrance skin exposure.

Female↗