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Biomedical subjects

S Song

Publications and source records attributed to S Song.

At least 181 records · Page 10Linked to original sources

[Paclitaxel (Tesu) as a single agent in the treatment of breast cancer].

OBJECTIVE: To evaluate the efficacy and the side effects of paclitaxel (Tesu) in breast cancer patients. METHODS: Tesu was administered at 175 mg/m2(170.9-210.8 mg/m2) to 22 patients with advanced breast cancer from March to July 1995. Tesu was given once in 21 days as one cycle, and the patients recieved 1-4 cycles (median: 3 cycles) of treatment. RESULTS: Tesu induced 3 complete responses and 11 partial responses. The duration of remission was 2-7 months (median 3.5 months). The most frequent toxicities associated with Tesu administration were leukopenia, alopecia and myalgias. CONCLUSION: Tesu as a single agent is effective in the treatment of breast cancer and the side effects are tolerable.

Adult↗

[Effects of icarrin on secretive function of cultured granulosa and adrenal cortical cells of rats].

Icarrin was added to cultured cells and the hormones in culture fluid were determined after 3 hours of incubation. The results showed that icarrin (30-1000 micrograms/L) could promote the estradiol production of granulosa cells. The most effective concentration was 100 micrograms/L. Icarrin also exerted a stimulatory effect on corticosterone production at the highest dosage (1000 micrograms/L).

Adrenal Cortex↗

[The study of color stability of ceramic stains subjected to glazing temperature].

Ceramic stains are used to modify the final colors of ceramic dental restorations. They are not color stable when subjected to glazing temperature. In order to understand the color change characteristics, the study tested the color stability of the five Vita VMK68 stains. The international color standard CIE1976LAB color system and CS-5 Spectrocolorimeter are used. The results indicate: significant color changes are noted for five stains; the color change characteristics among them are different; yellow-brown stain shows the most color unstability after firing.

Color↗

[The effect of systemic and local irradiation on wound macrophages and the repair promoting action of phenytoin sodium].

OBJECTIVE: To study the effect of systemic and local irradiation on wound macrophages (M phi) and the pair promoting action of phenytoin sodium on irradiation-impaired wound healing. METHODS: Wound M phi was collected by polyvinyl alcohol sponges which were implanted in a rat dorsum incision. The number of M phi, phagocytic function of wound M phi, and the release of tumor necrosis factor (TNT alpha) and interleukin-1 (IL-1) from wound M phi, and wound breaking strength (WBS) were respectively investigated. RESULTS: WBS was deceased after 6Gy systemic irradiation and 20Gy local irradiation, and phenytoin sodium improved WBS in normal wound and radiation-impaired wound. After 6Gy systemic irradiation the phagocytic function of wound M phi, the release of TNF alpha and IL-1 from wound M phi, as well as the number of M phi in wound, were significantly decreased on days 3, 5, 8 after wounding. After 20Gy local irradiation, the ratio of M phi in wound cells was significantly decreased on days 3, 5, 8, 13 after wounding, but the function of macrophage was not significantly decreased. Phenytoin sodium significantly increased the number of wound M phi, improved the phagocytic function of M phi, and the release of TNF alpha and IL-I from wound M phi on days 3, 5, 8 days after wounding despite the rats were radiated or not. CONCLUSION: The results indicated that the decrease of number and function of wound M phi play an important role in the impairment of early wound healing by systemic irradiation. Phenytoin sodium accelerated normal and irradiation-impaired wound healing by increasing the number of wound M phi and improving the M phi function.

Animals↗

[Clinical significance of expression of multidrug resistance gene in breast cancer tissue].

OBJECTIVES: To investigate the role of expression of multidrug resistance gene (mdr-1 gene) in chemotherapeutic resistance of breast cancer and to determine if expression of mdr-1 gene may act as an index for predicting chemotherapy response and prognosis. METHODS: Using reverse transcription-polymerase chain reaction (RT-PCR) technique, we determined the levels of mdr-1 mRNA in 82 breast cancer samples. RESULTS: Positive expressions of mdr-1 gene were 34.3% in 35 cases of untreated primary breast cancer and 59.0% in 47 cases of relapsed metastatic breast cancer, separately, and the difference was statistically significant (P < 0.05). In 28 cases of relapsed metastatic breast cancer of mdr-1 gene positive expression, 22(78.6%) were ever treated with MDR related drugs. Levels of mdr-1 gene expression of all 7 cases were higher after chemotherapy than before chemotherapy. Positive expressions were 16.7% and high grade positive expressions were 5.6% in 18 sensitive cases. Positive expressions were 71.4% and high grade positive expressions were 50.0% in 14 resistant cases. The difference was statistically significant (P < 0.01). There were no relations between expression of mdr-1 gene and ages, menopause status, lymphnode involvements, clinical stages, and estrogen receptor levels. CONCLUSION: The results indicated that retreated metastatic breast cancer is more extensively resistant than untreated primary breast cancer and acquired drug resistance is an important reason. Expression of mdr-1 gene seems to be a reference index for predicting response of chemotherapy.

Antineoplastic Agents↗

[The relationship between in vitro chemosensitivity of human breast cancer to MDR related drugs and expression of mdr-1 gene].

OBJECTIVE: To study the relationship between in vitro chemosensitivity of human breast cancer to MDR related drugs and expression of mdr-1 gene. METHODS: We measured the chemosensitivity of 56 human breast cancers to MDR related drugs by MTT assay in vitro and level of mdr-1 mRNA in these samples by RT-PCR technique. RESULTS: The expression of mdr-1 gene in the breast cancer resistant to drugs in vitro was increased significantly. The level of mdr-1 mRNA was not correlated with Imax%, but correlated with IC50 statistically. CONCLUSION: These results support that the increased expression of mdr-1 gene is a major cause of resistance to MDR related drugs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Characterization and quantitation of the apoproteins of high-density lipoprotein by capillary electrophoresis.

A method has been developed using capillary electrophoresis (CE) to quantitate plasma levels of apoprotein A-I (apoA-I) and apoprotein A-II (apoA-II) in high-density lipoprotein (HDL) samples. ApoA-I and apoA-II are resolved by CE in delipidated and non-delipidated HDL samples. Concentrations of apoA-I and apoA-II were calculated from their peak areas in the electropherogram. Results of the analysis of Sigma plasma standards (Controls 1 and 2) using CE are in good agreement with values obtained by Sigma using immunoturbidimetric assay. CE and reverse-phase high-performance liquid chromatography (RP-HPLC) were found to be complementary in the study of apoA-I and apoA-II. RP-HPLC resolves the isoforms of purified apoA-I and apoA-II, but it cannot resolve mixtures of them because the retention times of the isoforms overlap. CE separates apoA-I from apoA-II, but it does not resolve the isoforms. Matrix-assisted laser desorption/ ionization mass spectrometry was used to identify the isoforms of apoA-I and apoA-II by their molecular weight (M(r)) in fractions collected from RP-HPLC.

Apoproteins↗

Cloning and characterization of the gene encoding Halobacterium halobium adenylate kinase.

The gene (AK) encoding adenylate kinase (AK) of Halobacterium halobium was cloned. AK consisted of 648 bp and coded for 216 amino acids (aa). S1 mapping and primer extension experiments indicated that the transcription start point (tsp) was located immediately upstream from the start codon. The TAT-like promoter sequence was found at a position 20-24 bp upstream from tsp. The most striking property of the enzyme was a putative Zn finger-like structure with four cysteines. It might contribute to the structural stability of the molecule in high-salt conditions. Phylogenetic analysis indicated two lineages of the AK family, the short and long types which diverged a long time ago, possibly before the separation of prokaryotes and eukaryotes. Although the H. halobium AK belongs to the long-type AK lineage, it is located in an intermediary position between the two lineages of the phylogenetic tree, indicating early divergence of the gene along the long-type lineage.

Adenylate Kinase↗

Site-directed mutagenesis of putative catalytic and nucleotide binding sites in N10-formyltetrahydrofolate synthetase.

To determine the importance of specific amino-acid residues in catalysis and substrate binding by N10-formylH4 folate synthetase, one lysine and three histidine residues in the enzyme from Clostridium cylindrosporum were mutated to glutamine and serine residues, respectively. These residues, Lys-71, His-125, His-131, and His-268, are conserved in four bacterial and five eukaryotic proteins for which the amino-acid sequences are known. Previous evidence indicated that a histidine residue may play a role in catalysis and it has been proposed that Lys-71 could be a member of a putative nucleotide binding consenus sequence. The histidine mutations, H125S, H131S, and H268S, produced proteins that were unstable and were proteolytically degraded to different extents. No activity of purified H268S could be detected and the 240 kDa native tetramer was also absent. Activities of the H125S and H131S mutants could be measured and the Km values of the substrates were similar to those for the wild-type enzyme. It is concluded that the mutations resulted in monomers that do not fold properly and/or do not associate to the active tetramer and, as a consequence, are susceptible to intracellular proteolytic digestion. On the other hand, the K71Q mutation did not produce proteolyzed material. The resulting protein had a kcat value which was reduced by a factor of 3.3 x 10(-4). Km values of the substrates were not affected, nor were the affinty constants for MgATP and H4PteG3. CD and fluorescence spectra demonstrated that little change in the tertiary structure of the protein had occurred as a result of the mutation. The monomer form of K71Q was less stable than the monomer of the wild-type enzyme and reassociated less efficiently than the wild-type. From these results it is suggested that Lys-71 plays a critical role in catalysis by N10-formylH4 folate synthetase and that this residue may reside at an intersubunit interface.

Amino Acid Sequence↗

The unique endometrial expression and genomic organization of the porcine IGFBP-2 gene.

The insulin-like growth factor-binding proteins (IGFBPs-1-6) modulate the mitogenic and differentiative actions of the IGFs and may have IGF-independent functions. This study examined the gene expression and pregnancy-regulation of the IGF/IGFBP system in porcine uterine endometrium and myometrium during the periimplantation period and later stages of pregnancy. Endometrial IGFBP-2 mRNA abundance exhibited stage of pregnancy-dependent induction; whereas little or no IGFBP-2 mRNA was found in myometrium. IGFBP-2 protein was immunolocalized to the endometrial glandular and luminal epithelia (staining on day 60 > day 12) with minimal or no immunostaining of uterine stroma observed. IGFBP-3 and IGFBP-4 transcript levels became elevated in endometrium after implantation; whereas, IGFBP-5 and IGFBP-6 mRNAs were in greater abundance in periimplantation than post-implantation endometrium. IGFBP-1 transcripts, in contrast, could not be identified in porcine endometrium or myometrium of pregnancy. As a pre-requisite to understanding the pregnancy-induction and endometrial-specificity of the uterine-expressed IGFBP-2 gene, cosmids encompassing the pig IGFBP-2 chromosomal locus were isolated and characterized. This gene is comprised of four exons that span > 29 kb and encode a 316 amino acid precursor protein. All four exons were found to be G/C rich with exon 1 and immediate 5' flank exhibiting hallmarks of a CpG island. This latter region was devoid of TATA and CAAT motifs. Results identify the preferential endometrial expression of different IGFBP genes at either the periimplantation or post-implantation periods, perhaps reflecting distinct actions of these proteins at the embryo-maternal and feto-maternal interfaces, respectively. Interactions of steroid receptors, endometrial transcription factors and their corresponding cis elements may confer the unique uterine expression of the IGFBP-2 gene.

Amino Acid Sequence↗

An improved quantitative RT-PCR fluorescent method for analysis of gene transcripts in the STS-65 space shuttle experiment.

We describe a reverse transcription polymerase chain reaction (RT-PCR) technique using fluorescent dUTP to examine changes in mRNA level in samples. In this procedure, the amplified product is identified by the fluorescent detection system in an automated DNA sequencer, and if the MW of the DNA/RNA or the fluorescent dye is different, several samples can be analyzed in a single lane. The basis for this technique is similar to that of radiolabeled methods, and we applied this technique for the comparison of the expression level of the rat c-myc gene in osteoblasts exposed to microgravity and unit gravity conditions. Using the fluorescent- and radiolabeled methods, the level of rat c-myc mRNA were compared quantitatively and the results demonstrated that the c-myc expression level was not altered by microgravity. Therefore, this fluorescent RT-PCR technique is useful for gene expression analysis particularly when the samples are limited, such as in space flight experiments. The method also allows for rapid assessment of mRNA changes in many samples simultaneously.

Animals↗

Loss of deoxcytidine kinase expression and tetraploidization of HL60 cells following long-term culture in 1,25-dihydroxyvitamin D3.

Development of drug resistance is a major problem in attempts to control the growth of neoplastic cell populations. The resistance can he either inherent or acquired by an exposure to a chemotherapeutic drug. The available models for study of these phenomena have not led to major improvements in the therapy for human cancers. Therefore, in order to develop a new model for such studies, we have exposed human myeloid leukemia cells HL60 to increasing concentrations of 1,25-dihydroxyvitamin D3 (1,25D3) and characterized the emerging new phenotypes of these cells over a period of 4 years. During the stepwise development of resistance only cells which did not adhere to the flask walls were passaged. Beginning at 30 nM 1,25D3 the sublines became resistant to the differentiation-inducing and growth-retarding properties of 1,25D3 even at 400 nM. Also, their growth rates in 1,25D3-free media increased. In addition, beginning at 40 nM 1,25D3 the sublines acquired resistance to 5-beta-D-arabinocytosine (araC) due to the lack of expression of the deoxycytidine kinase gene. The araC-resistant sublines were also near-tetraploid, as judged by their DNA content. When grown in 1,25D3-free long-term culture the phenotype was essentially stable. The development of cross-resistance to araC during growth in the presence of an unrelated compound (i.e., 1,25D3) shows that in some instances an apparently inherent drug resistance may in fact he due to a metabolic defect resulting from an exposure to another agent.

Autoradiography↗

IL-10 cooperates with TNF-alpha to activate HIV-1 from latently and acutely infected cells of monocyte/macrophage lineage.

IL-10 is elevated in HIV-1-infected individuals and has been implicated in disease progression. In this study, we investigated the effects of IL-10 on the activation of HIV-1 from infected monocytes and macrophages. Although IL-10 alone did not induce HIV-1 replication, in the presence of TNF-alpha, IL-10 markedly enhanced virion production from a chronically infected promonocytic cell line (U1) and in acutely infected monocyte-derived macrophages. Neutralizing mAbs to IL-10 and TNF-alpha indicated that both cytokines were essential for the induction and were required to generate a synergistic increase in virus expression. The effects of the two cytokines were distinguishable functionally since pretreatment with TNF-alpha attenuated the cytokine cooperativity, while pretreatment with IL-10 potentiated their cooperativity, suggesting that IL-10 and TNF-alpha play different roles in the activation of virus. Northern blot analysis as well as Ab blocking and cytokine secretion studies indicated that the induction of either endogenous TNF-alpha or IL-10 was not involved in the cooperativity, nor was an up-regulation of TNF-alpha receptors. In combination with TNF-alpha, IL-10 stimulated activating protein-1 (AP-1) and nuclear factor (NF)-kappa B binding activities and cooperated to increase HIV-1 steady-state mRNA levels and enhance long terminal repeat-directed transcription through activation of the NF-kappa B binding sites, suggesting the IL-10 effect occurs at least in part at the transcriptional level. These results indicate that IL-10, in addition to down-regulating the cellular immune response to HIV-1, may also play a role in TNF-alpha-mediated activation of HIV-1 replication in the monocyte/macrophage lineage.

Base Sequence↗

Failure rates of leads, pulse generators, and programmers have not diminished over the last 20 years: formal monitoring of performance is still needed. BILITCH Registry and STIMAREC.

Formal Monitoring of Performance is Still Needed. In order to detect trends in the number of device or component failures that have occurred among permanent pacemaker systems since the 1970s, we reviewed the data of the five largest pacemaker manufacturers from the Bilitch Registry of permanent pacemaker pulse generators, the Stimarec failure registry, the general accounting office summaries of the United States Veterans Administration (VA) Registry of Pacemaker Leads, and the Implantable Lead Registry, from the Cleveland Clinic Lead registry, and the recalls and safety alerts issued by the United States Food and Drug Administration (FDA) over the last 20 years. The definition of failure followed the criterion, or criteria, developed within each registry and differed significantly between the registries. The 20-year period between 1976 and 1995 was divided into 5-year quartiles (QT): QT 1 = 1976-1980; QT2 = 1981-1985; QT3 = 1986-1990; and QT4 = 1991-1995. For pulse generators, the number of models with failures in each quartile in the Bilitch Registry were: QT 1 = 9; QT 2 = 11; QT3 = 17; QT4 = 13. In Stimarec, the number of units reported as having reached a dangerous condition were: QT1 = 710; QT2 = 212; QT3 = 114; QT4 = 310. From the FDA reports, the number of units included in recalls or safety alerts were: QT3 = 6,085; QT4 = 135,766. For permanent pacemaker leads, the numbers of failed or dangerous leads recorded in Stimarec were: QT3 = 16; QT4 = 32. In the VA Registry, the number of models having a below average survival was 2/92 (2.7%). In the Implantable Lead Registry, the number of models having a below average survival was 3/21 (14%). In the Cleveland Clinic series, 6/13 (46%) of lead models were recognized to have some failure involving the conductor, insulation, or connector. In the FDA reports, the number of leads involved in either recall or safety alert were: QT3 = 20,354; QT4 = 332,105. For programmers, the number of units involved either in a recall or safety alert were: QT3 = 11,124; QT4 = 3,528. In all of these series, each of the five largest manufacturers had some models or units involved in each time period. This review of programs has revealed: 1. The incidence of failures, recalls, or safety alerts did not decline over time; and 2. Despite changes in technology, formal monitoring of pacemaker systems is still warranted.

Electric Power Supplies↗

Helper virus-free transfer of herpes simplex virus type 1 plasmid vectors into neural cells.

Herpes simplex virus type 1 (HSV-1) plasmid vectors have promise for genetic intervention in the brain, but several problems caused by the helper virus have compromised their utility. To develop a helper virus-free packaging system for these vectors, the DNA cleavage/packaging signals were deleted from a set of cosmids that represents the HSV-1 genome. Following cotransfection into cells, this modified cosmid set supported replication and packaging of vector DNA. However, in the absence of the DNA cleavage/packaging signals, the HSV-1 genome was not packaged, and consequently vector stocks were free of detectable helper virus. In the absence of helper virus, the vectors efficiently infected rat neural cells in culture or in the brain with minimal cytopathic effects. beta-galactosidase-positive cells were observed for at least 1 month in vivo, and vector DNA persisted for this period. This system may facilitate studies on neuronal physiology and potential therapeutic applications.

Animals↗