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Biomedical subjects

Y Fan

Publications and source records attributed to Y Fan.

At least 127 records · Page 7Linked to original sources
PubMed1998

Phenotype and genotype of advanced premalignant head and neck lesions after chemopreventive therapy.

BACKGROUND: The goal of chemoprevention is to reduce the risk of cancer development by reversing or blocking the tumorigenic process through the use of pharmacologic or natural agents. To determine the potential role of genetic alterations in assessing cancer risk and in evaluating the efficacy of chemopreventive agents, we studied 22 patients with advanced premalignant lesions of the head and neck who were part of a prospective cancer prevention trial that is investigating a regimen of 13-cis-retinoic acid, interferon alfa, and alpha-tocopherol administered for 12 months or until disease progression. METHODS: We used polymerase chain reaction analysis of microsatellite DNA sequences in cells from precancerous lesions to determine the frequencies of genetic alterations--namely, loss of heterozygosity (LOH) and microsatellite instability--at chromosomal loci that are commonly deleted in head and neck cancer. RESULTS: Prior to treatment, 17 (81%) of 21, eight (44%) of 18, and eight (42%) of 19 patients who were informative (i.e., heterozygous) at chromosomes 9p21, 3p14, and 17p13, respectively, exhibited LOH in at least one of their lesion biopsy specimens. Among nine patients who exhibited LOH at chromosome 9p21 in pretreatment biopsy specimens and who had completed at least 5 months of therapy, the genetic loss persisted in eight--including three of the four patients who exhibited complete histologic responses (i.e., no evidence of dysplasia in their biopsy specimens). IMPLICATION: Our data suggest that clinical and histologic assessments of the response to chemopreventive agents may be insufficient to determine their efficacy and that critical genetic alterations could be used as independent biomarkers to augment the ability to evaluate the efficacy of such agents.

Antineoplastic Agents↗
PubMed1998

[Identification of a mutation hotspot in exon 8 of Wilson's disease gene by cycle sequencing].

OBJECTIVE: To screen for mutation hotspot of Wilson's disease (WD) gene in Chinese. METHODS: Cycle sequencing was used to detect mutation in exon 8 of WD gene in 30 patients with WD. RESULTS: The same missense mutation, Arg778Leu, was identified in 14 WD patients, four of which were homozygous and the others were heterozygous for this mutation. The frequency of this mutation was 30%. CONCLUSION: The codon 778(CGG-->CTG) of exon 8 in WD gene was one of mutation hotspots in Chinese.

Adolescent↗
PubMed1998

Mechanism of action of eukaryotic DNA topoisomerase I and drugs targeted to the enzyme.

DNA topoisomerase I is essential for cellular metabolism and survival. It is also the target of a novel class of anticancer drugs active against previously refractory solid tumors, the camptothecins. The present review describes the topoisomerase I catalytic mechanisms with particular emphasis on the cleavage complex that represents the enzyme's catalytic intermediate and the site of action for camptothecins. Roles of topoisomerase I in DNA replication, transcription and recombination are also reviewed. Because of the importance of topoisomerase I as a chemotherapeutic target, we review the mechanisms of action of camptothecins and the other topoisomerase I inhibitors identified to date.

Antineoplastic Agents↗
PubMed1998

Suppression of human fibrosarcoma cell growth by transcription factor, Egr-1, involves down-regulation of Bcl-2.

Previously, we showed that the transcription factor Egr-1 suppressed the proliferation of v-sis transformed NIH3T3 cells and also a number of human tumor cells. Here, we investigate the possible mechanisms responsible for this function. We show that transfected Egr-1 in human fibrosarcoma cells HT1080 leads to down-regulation of Bcl-2. Transient CAT transfection assays reveal that expression of Egr-1 suppresses Bcl-2 promoter activity in a dose-dependent manner. Furthermore, overexpression of Bcl-2 in Egr-1-expressing HT1080 cells enhanced cell proliferation in monolayer culture and increased anchorage-independent growth. Our results suggest that suppression of tumor cell proliferation by Egr-1 may be at least partially mediated through the down-regulation of Bcl-2.

Blotting, Western↗
PubMed1998

Gene expression of monocyte chemoattractant protein-1 in giant cell tumors of bone osteoclastoma: possible involvement in CD68+ macrophage-like cell migration.

Giant cell tumor of bone (GCT) is one of a few neoplasms in which the macrophage/osteoclast precursor cells and osteoclast-like giant cells infiltrate the tumor mass. Monocyte chemoattractant protein 1 (MCP-1) is a potent chemotactic factor specific for monocytes. In search of relevant cytokines that may enhance the recruitment of these reactive cells, we evaluated the localization and regulation of MCP-1 mRNA and protein in GCT by using Northern blot analysis, in situ hybridization and immunohistochemistry. We also determined whether conditioned medium obtained from GCT cultures can recruit human peripheral blood monocytes (CD68+) in an in vitro chemotactic assay. Using Northern blot analysis, we detected the specific gene transcript for MCP-1 in all GCT samples tested. In situ hybridization and immunohistochemistry revealed that both MCP-1 gene transcript and protein were consistently present in the cytoplasm of stromal-like tumor cells of GCT. Treatment of mononuclear cells from GCT at third passage with TGF-beta1 for 24 h increased the level of MCP-1 mRNA in a dose-dependent manner, with the maximum effect at 1 ng/ml. Conditioned media from GCT cultures promoted the chemotactic migration of CD68+ peripheral monocytes, an activity which was abolished by the addition of MCP-1 antibody to the conditioned medium. Thus, the results of this study suggest that recruitment of CD68+ macrophage-like cells may be due to the production MCP-1 by stromal-like tumor cells. These CD68+ cells may originate from peripheral blood and could have the capability of further differentiating into osteoclasts in the tumor.

Antigens, CD↗
PubMed1998

Molecular modeling studies of the DNA-topoisomerase I ternary cleavable complex with camptothecin.

The present studies provide a three-dimensional model for the postulated ternary cleavable complex of topoisomerase I (top1), DNA, and camptothecin (CPT). Molecular simulations were done using the AMBER force field. The results suggest that a ternary cleavable complex might be stabilized by several hydrogen bonds in the binding site. In this proposed "drug-stacking" model, CPT is pseudointercalated in the top1-linked DNA cleavage site and interacts with the protein near its catalytic tyrosine through hydrogen bonding and stacking. The structural model is consistent with the following experimental observations: (i) the N3 position of the 5' terminal purine of the cleaved DNA strand is readily alkylated by 7-chloromethyl 10,11-methylenedioxy CPT; (ii) CPT generally tolerates substituents at positions 7, 9, and 10 but is inactivated by additions at position 12; (iii) 10,11-methylenedioxy (MDO) CPT is much more potent than 10,11-dimethoxy (DMO) CPT; (iv) the lactone portion of CPT is essential for top1 inhibitory activity; (v) 20S derivatives of CPT are much more potent than the 20R analogues; (vi) a catalytic tyrosine hydroxyl in top1 covalently links to the 3' terminal base, T, of the cleaved DNA strand; and (vii) top1 mutation Asn722Ser leads to CPT resistance. A total of 18 camptothecin derivatives with different DNA cleavage potencies were docked into the hypothetical cleavable complex binding site to test and refine the model. These studies provide insight into a possible mechanism of top1 inhibition by CPT derivatives and suggest rational approaches for the design of new CPT derivatives.

Amino Acid Substitution↗
PubMed1998

[Rapid selection of the gradually shortened DNA clones by using PCR amplification].

OBJECTIVE: To establish a simple technique with which the gradually shortened DNA clones can be selected rapidly and accurately so that the sequencing and identification of the full length cDNA or longer DNA fragments can be performed as quick as possible. METHODS: Primers were designed according to the sequence flanking the multiple cloning site of pGEM vector and were used to amplify the inserted fragments in a series of deletion sub-clones originated from a clone. with longer DNA insert fragment. These sub-clones which contain the gradually shortened fragments can be selected directly. This method was compared with the routine method in which the restriction endonuclease was used to digest DNA samples. RESULTS: A series of deletion sub-clones were identified accurately with this new method and the cycle sequencing could be performed on these PCR products as well. This method was characteristic of more accurate, more simple and less time-consuming, compared with the routine method. CONCLUSION: The method presented is very effective for rapid selection of the gradually shortened inserted fragments constructed in pGEM vector. It can greatly save time and materials, and the strategy in the report could also fit for selecting the clones containing gradually shortened fragments in other plasmid vectors.

DNA, Complementary↗
PubMed1998

An analysis of sex and breeding stage differences in prolactin binding activity in brain and hypothalamic GnRH concentration in Wilson's phalarope, a sex role-reversed species.

Wilson's Phalarope (Phalaropus tricolor) is a sex role-reversed species in which incubation of eggs and care of young is performed exclusively by the male. Plasma levels of prolactin (PRL), the hormone most associated with parental care in birds, are higher in incubating males than in nonincubating males or females. Conversely, plasma testosterone levels are reduced in males during incubation. In an attempt to characterize the physiological basis of this unusual parental care system we used quantitative film autoradiography and densitometry to measure the specific binding in vitro of 125I-ovine PRL to 12 brain regions in females, nonincubating males, and incubating males during the normal breeding season. We also measured hypothalamic chicken gonadotropin-releasing hormone I (cGnRH-I) in three brain areas in these same birds, as well as plasma levels of PRL and testosterone. Analysis revealed that cGnRH-I concentrations in the preoptic area and plasma testosterone levels were significantly lower in incubating males than in nonincubating males. Specific binding of 125I-ovine PRL was detected in choroid plexus and in several diencephalic brain regions of both sexes, with highest binding activity recorded in the dorsolateral thalamus, medial habenula, nucleus subrotundus, and preoptic area. When adjustments were made for the large number of comparisons performed, specific binding did not vary significantly by sex or breeding stage in any single brain region. However, average specific binding values in nonincubating males exceeded those of incubating males in 9 of the 11 PRL-sensitive regions examined. Increased occupancy of the receptor by endogenous PRL during incubation could have contributed to this result, since plasma PRL levels were elevated in incubating males. In addition, PRL binding activity in several of these brain regions tended to correlate negatively with plasma PRL. The two exceptions to this general pattern were the preoptic area and the lateral septum, where mean specific binding was 14-15% higher in incubating males than in nonincubating males. This raises the interesting possibility that PRL sensitivity is up-regulated during incubation in some regions of the male phalarope brain, such as the preoptic area and lateral septum, that have been implicated in PRL-modulated changes in behavior and reproductive activity during this breeding stage.

Animals↗
PubMed1998

Multiple forms of GnRH are released from perifused medial basal hypothalamic/preoptic area (MBH/POA) explants in birds.

Both chicken gonadotropin-releasing hormones I and II (cGnRH I and II) were detected in abundant quantity by radioimmunoassay of extracts of Japanese quail medial basal hypothalamic/preoptic area (MBH/POA) fragments that included the median eminence (ME) region. However, in radioimmunoassayed extracts of Japanese quail ME alone, the concentration of cGnRH I greatly exceeded that of cGnRH II (approximately 450 pg/ME vs < 10 pg/ME). Likewise, cGnRH I and II were released into perifusates from quail an turkey MBH/POA explants maintained in short-term perifusion. Release of both forms occurred whether or not explants included the ME region, i.e., from quail POA explants did not include the ME or from turkey MBH/POA explants from which the ME region had been dissected out. This indicates that neuropeptides released from areas other than the ME can be a major source of neuropeptides detected in perifusates. Further, release of cGnRH I was altered following the addition of norepinephrine to perfusion media, whereas cGnRH II release was unaffected, again, whether or not explants included the ME. These results demonstrate that the release of neurohemoral substances from perifused explants cannot be assumed to represent regulated secretion from the ME.

Animals↗
PubMed1998

Egr-1 inhibits apoptosis during the UV response: correlation of cell survival with Egr-1 phosphorylation.

UV irradiation of normal or immortalized cells induces a rapid increase in the expression of several transcription factors and is thought to serve a protective function. The human fibrosarcoma cell line, HT1080 clone H4, expresses almost undetectable levels of Egr-1 and does not respond to UV-C irradiation by the induction of Egr-1. The H4 cells are hypersensitive to UV which induces apoptosis and reduces clonogenicity. The introduction of exogenous Egr-1 into H4 (H4E9 and H4E4 cell-lines) confers protection from UV damage as measured by a number of assays. In both NIH3T3 (with inducible Egr-1) and H4E9 (constitutive Egr-1) cells, UV irradiation gave enhanced transactivation of Egr-1 reporters that correlated with phosphorylated Egr-1. Studies using inhibitors indicated that protein kinase-C and tyrosine kinases are involved in the anti-apoptotic effects of Egr-1 after UV damage. This is the first description of a biological effect of phosphorylated Egr-1.

3T3 Cells↗
PubMed1998

Mining the National Cancer Institute Anticancer Drug Discovery Database: cluster analysis of ellipticine analogs with p53-inverse and central nervous system-selective patterns of activity.

The United States National Cancer Institute conducts an anticancer drug discovery program in which approximately 10,000 compounds are screened every year in vitro against a panel of 60 human cancer cell lines from different organs. To date, approximately 62,000 compounds have been tested in the program, and a large amount of information on their activity patterns has been accumulated. For the current study, anticancer activity patterns of 112 ellipticine analogs were analyzed with the use of a hierarchical clustering algorithm. A dramatic coherence between molecular structures and their activity patterns could be seen from the cluster tree: the first subgroup (compounds 1-66) consisted principally of normal ellipticines, whereas the second subgroup (compounds 67-112) consisted principally of N2-alkyl-substituted ellipticiniums. Almost all apparent discrepancies in this clustering were explainable on the basis of chemical transformation to active forms under cell culture conditions. Correlations of activity with p53 status and selective activity against cells of central nervous system origin made this data set of special interest to us. The ellipticiniums, but not the ellipticines, were more potent on average against p53 mutant cells than against p53 wild-type ones (i.e., they seemed to be "p53-inverse") in this short term assay. This study strongly supports the hypothesis that "fingerprint" patterns of activity in the National Cancer Institute in vitro cell screening program encode incisive information on the mechanisms of action and other biological behaviors of tested compounds. Insights gained by mining the activity patterns could contribute to our understanding of anticancer drugs and the molecular pharmacology of cancer.

Antineoplastic Agents↗
PubMed1998

The Polycomb group in Caenorhabditis elegans and maternal control of germline development.

Four Caenorhabditis elegans genes, mes-2, mes-3, mes-4 and mes-6, are essential for normal proliferation and viability of the germline. Mutations in these genes cause a maternal-effect sterile (i.e. mes) or grandchildless phenotype. We report that the mes-6 gene is in an unusual operon, the second example of this type of operon in C. elegans, and encodes the nematode homolog of Extra sex combs, a WD-40 protein in the Polycomb group in Drosophila. mes-2 encodes another Polycomb group protein (see paper by Holdeman, R., Nehrt, S. and Strome, S. (1998). Development 125, 2457-2467). Consistent with the known role of Polycomb group proteins in regulating gene expression, MES-6 is a nuclear protein. It is enriched in the germline of larvae and adults and is present in all nuclei of early embryos. Molecular epistasis results predict that the MES proteins, like Polycomb group proteins in Drosophila, function as a complex to regulate gene expression. Database searches reveal that there are considerably fewer Polycomb group genes in C. elegans than in Drosophila or vertebrates, and our studies suggest that their primary function is in controlling gene expression in the germline and ensuring the survival and proliferation of that tissue.

Amino Acid Sequence↗
PubMed1998

[Improving the bonding strength of castable ceramic crowns].

To study the influence of bonding agent on fracture strength of Plat-II castable ceramic crowns bonded to molars, we tested the specimens in vitro with Panavia 21 resin bonding agent and porcelite dual cure cement. The results showed that the fracture loading (845.8 +/- 137.1 N) of crowns bonded with Panavia 21 bonding agent was higher than that (534.0 +/- 58.7 N) of crows bonded with porcelite dual cure cement. The difference between the two agents was statistically significant (P < 0.05). The crowns bonded with Panavia 21 agent had higher strength than bite forces. These suggest that costable ceramic crowns could be bonded with Panavia 21 resin agent in clinical practice.

Crowns↗
PubMed1998

[Pulmonary complications occurring after allogeneic bone marrow transplantation].

OBJECTIVE: To explore the risk factors for and pathogenesis of pulmonary complications (PC) occurred after allogeneic bone marrow transplantation (allo-BMT). METHODS: The PC in 185 patients undergone allo-BMT were analyzed. RESULTS: Ninety-three PC episodes were observed in 89 patients and most of them were due to infections, including bacterial pneumonia (n = 27), interstitial pneumonia (n = 7), pulmonary fungus disease (n = 16), tuberculosis (n = 4), obstructive lung disease (n = 2), pulmonary edema (n = 2), lung abscess (n = 1) and 34 episodes caused by two or more pathogens. The overall mortality for PC was 12.43% (23/185). CONCLUSION: The risk factors for PC occurred after allo-BMT were not related to age and sex of recipients, bone marrow status before BMT, conditioning regimen and pulmonary function. Graft-versus-host-disease significantly increased the morbidity and mortality of PC after allo-BMT.

Acute Disease↗
PubMed1998

[Polymerase chain reaction technique in monitoring treatment of bacillary pulmonary tuberculosis].

OBJECTIVE: To explore the relationship between sputum Mycobacterium tuberculosis as well as its DNA negative conversion and relapse in bacillary pulmonary tuberculosis during chemotherapy and 2 years after completion of treatment, and to evaluate the value of polymerase chain reaction (PCR) technique in monitoring the efficacy of treatment. METHOD: Eighty-seven patients with bacillary pulmonary tuberculosis were monthly examined by PCR technique, smear and culture methods, and were followed up for 2 years after treatment. RESULT: The duration of sputum negative conversion by PCR technique was 1-3 months later than that by smear and culture methods. The more the sputum bacteria, the longer the duration of PCR positive results. Positive PCR results maintained in 10 out of 87 patients for more than 1 year, among them 3 (30%) relapsed respectively at 8, 12 and 16 months after treatment. One PCR negative conversion case relapsed at 18 months after treatment. These 4 cases who regained sputum positive results and showed deterioration in chest X-ray films were admitted to hospital again. CONCLUSION: PCR technique is more practical than smear and culture methods in monitoring efficacy of the treatment of bacillary pulmonary tuberculosis, and is useful for evaluating cases with possible relapse.

Adult↗
PubMed1998

[Seasonal and sexual variety of Ginkgo flavonol glycosides in the leaves of Ginkgo biloba L].

HPLC methods have been developed for the determination of Ginkgo flavonol glycosides in the Ginkgo biloba leaves obtained from May to November in the fallen leaves and in the leaves obtained from female and male trees. The method includes hydrolysis of the leaves and subsequent quantitative chromatographic assay of the aglycones, followed by calculation of Ginkgo flavonol glycosides content. The result shows that the leaves obtained in May have the highest content of 0.96%, and then the content decreases from May to August, and from August to November remains almost the same, that is 0.5% also. Fallen leaves have the lowest content of 0.44%. The content range is 0.96% to 0.44%. Male trees have higher content of glycosides than female trees.

Chromatography, High Pressure Liquid↗