Dinucleotide repeat polymorphism in the canine retinoblastoma (RB1) gene.
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Animals↗
Biomedical subjects
Y Cao
Publications and source records attributed to Y Cao.
Using novel phylogenetic methods to evaluate mammalian mtDNA, including amino acid-invariant sites-LogDet plus site stripping, to detect internal conflicts in the data, with special reference to the positions of hedgehog, armadillo, and elephant.
We look at the higher-order phylogeny of mammals, analyzing in detail the complete mtDNA sequences of more than 40 species. We test the support for several proposed superordinal relationships. To this end, we apply a number of recently programmed methods and approaches, plus better-established methods. New pairwise tests show highly significant evidence that amino acid frequencies are changing among nearly all the genomes studied when unvaried sites are ignored. LogDet amino acid distances, with modifications to take into account invariant sites, are combined with bootstrapping and the Neighbor Joining algorithm to account for these violations of standard models. To weight the more slowly evolving sites, we exclude the more rapidly evolving sites from the data by using "site stripping". This leads to changing optimal trees with nearly all methods. The bootstrap support for many hypotheses varies widely between methods, and few hypotheses can claim unanimous support from these data. Rather, we uncover good evidence that many of the earlier branching patterns in the placental subtree could be incorrect, including the placement of the root. The tRNA genes, for example, favor a split between the group hedgehog, rodents, and primates versus all other sequenced placentals. Such a grouping is not ruled out by the amino acid sequence data. A grouping of all rodents plus rabbit, the old Glires hypothesis, is also feasible with stripped amino acid data, and rodent monophyly is also common. The elephant sequence allows confident rejection of the older taxon Ferungulata (Simpson, 1945). In its place, the new taxa Scrotifera and Fereuungulata are defined. A new likelihood ratio test is used to detect differences between the optimal tree for tRNA versus that for amino acids. While not clearly significant as made, some results indicate the test is tending towards significance with more general models of evolution. Individual placement tests suggest alternative positions for hedgehog and elephant. Congruence arguments to support elephant and armadillo together are striking, suggesting a superordinal group composed of Xenarthra and African endemic mammals, which in turn may be near the root of the placental subtree. Thus, while casting doubt on some recent conclusions, the analyses are also unveiling some interesting new possibilities.
Animals↗
Assessing the Cretaceous superordinal divergence times within birds and placental mammals by using whole mitochondrial protein sequences and an extended statistical framework.
Using the set of all vertebrate mtDNA protein sequences published as of May 1998, plus unpublished examples for elephant and birds, we examined divergence times in Placentalia and Aves. Using a parsimony-based test, we identified a subset of slower evolutionary rate placental sequences that do not appear to violate the clock assumption. Analyzing just these sequences decreases support for Marsupionta and the carnivore + perissodactyl group but increases support for armadillo diverging earlier than rabbit (which may represent the whole Glires group). A major theme of the paper is to use more comprehensive estimates of divergence time standard error (SE). From the well-studied horse/rhino split, estimated to be 55 million years before present (mybp), the splitting time within carnivores is confidently shown to be older than 50 million years. Some of our estimates of divergence times within placentals are relatively old, at up to 169 million years, but are within 2 SE of other published estimates. The whale/cow split at 65 mybp may be older than commonly assumed. All the sampled splits between the main groups of fereuungulates (the clade of carnivores, cetartiodactyls, perissodactyls, and pholidotes) seem to be distinctly before the Cretaceous/Tertiary boundary. Analyses suggest a close relationship between elephants (representing Afrotheria) and armadillos (Xenarthra), and our timing of this splitting is coincident with the opening of the South Atlantic, a major vicariant event. Recalibrating with this event (at 100 mybp), we obtain younger estimates for the earliest splits among placentals. Divergence times within birds are also assessed by using previously unpublished sequences. We fail to reject a clock for all bird taxa available. Unfortunately, available deep calibration points for birds are questionable, so a new calibration based on the age of the Anseriform stem lineage is estimated. The divergence time of rhea and ostrich may be much more recent than commonly assumed, while that of passerines may be older. Our major concern is the rooting point of the bird subtree, as the nearest outgroup (alligator) is very distant.
Animals↗
The effect of commencing combination antiretroviral therapy soon after human immunodeficiency virus type 1 infection on viral replication and antiviral immune responses.
Twelve subjects were treated with zidovudine, lamivudine, and ritonavir within 90 days of onset of symptoms of acute infection to determine whether human immunodeficiency virus type 1 (HIV-1) infection could be eradicated from an infected host. In adherent subjects, with or without modifications due to intolerance, viral replication was suppressed during the 24-month treatment period. Durable suppression reduced levels of HIV-1-specific antibodies and cytotoxic T lymphocyte responses in selected subjects. Proviral DNA in mononuclear cells uniformly persisted. The persistence of HIV-1 RNA expression in lymphoid tissues and peripheral blood mononuclear cells suggests that elimination of this residual pool of virus should be achieved before considering adjustments in antiretroviral therapeutic regimens. In addition, given the reduction in levels of virus-specific immune responses, it would seem prudent to consider enhancing these responses using vaccine strategies prior to the withdrawal of antiviral therapy.
Acquired Immunodeficiency Syndrome↗
Interleukin-18 acts as an angiogenesis and tumor suppressor.
Interleukin-18 (IL-18), also called interferon-gamma (IFN-gamma)-inducing factor, has recently been characterized as a potent IFN-gamma-inducing cytokine. We now report that IL-18 is a novel antiangiogenic and antitumor cytokine. In vitro, IL-18 specifically inhibits fibroblast growth factor-2-stimulated proliferation of capillary endothelial cells. In vivo, IL-18 is sufficiently potent to suppress the fibroblast growth factor-induced corneal neovascularization by systemic administration in mice. This cytokine also inhibits embryonic angiogenesis in the chick chorioallantoic membrane assay. Systemic and intralesional administrations of IL-18 produce a significant suppression of the growth of murine T241 fibrosarcoma in syngeneic C57Bl6/J and immunodeficient SCID mice. The antitumor effect appears to be potent because an average of >75% inhibition of primary tumor growth was observed at a dose of 50 microg/kg/day. In cell culture, murine T241 fibrosarcoma cells are insensitive to recombinant IL-18 at concentrations that significantly inhibit endothelial cell proliferation. Immunohistochemical studies of tumor tissues reveal hypovascularization of the IL-18-treated tumors. These results suggest that IL-18 may participate in the regulation of a switch of tumor angiogenesis.-Cao, R., Farnebo, J., Kurimoto, M., Cao, Y. Interleukin-18 acts as an angiogenesis and tumor suppressor.
Animals↗
Decay kinetics of human immunodeficiency virus-specific effector cytotoxic T lymphocytes after combination antiretroviral therapy.
Little is known of the changes in human immunodeficiency virus type 1 (HIV-1)-specific effector cytotoxic T lymphocytes (CTL) after potent antiretroviral therapy. Using HLA/peptide tetrameric complexes, we show that after starting treatment, there are early rapid fluctuations in the HIV-1-specific CTL response which last 1 to 2 weeks. These fluctuations are followed by an exponential decay (median half-life, 45 days) of HIV-1-specific CTL which continues while viremia remains undetectable. These data have implications for the immunological control of drug-resistant virus.
ADP-ribosyl Cyclase↗
Adaptation of very virulent infectious bursal disease virus to chicken embryonic fibroblasts by site-directed mutagenesis of residues 279 and 284 of viral coat protein VP2.
The full-length RNA genomes of a chicken embryonic fibroblast (CEF)-nonpermissive, very virulent infectious bursal disease virus (IBDV) (strain HK46) were amplified into cDNAs by reverse transcription-PCR. The full-length cDNAs were sequenced and subcloned into a eukaryotic expression vector, from which point mutations were introduced into the VP2 region by site-directed mutagenesis. The wild-type and mutated plasmids were transfected directly into CEFs to examine their ability to generate CEF-permissive recombinant viruses. Substitution of amino acid residues 279 (Asp-->Asn) and 284 (Ala-->Thr) of the VP2 protein yielded a recombinant virus which was able to be passaged in CEFs, whereas the wild-type cDNAs and an amino acid substitution at residue 330 (Ser-->Arg) of the VP2 protein alone did not yield viable virus. The results indicated that mutation of other viral proteins, including VP1, VP3, VP4, and VP5, was not required for CEF adaptation of the virus. The same approach may be used to produce CEF-adapted strains from newly evolved IBDVs or to manipulate the antigenicity of the virus.
Amino Acid Sequence↗
Cortical language activation in stroke patients recovering from aphasia with functional MRI.
BACKGROUND AND PURPOSE: Two mechanisms for recovery from aphasia, repair of damaged language networks and activation of compensatory areas, have been proposed. In this study, we investigated whether both mechanisms or one instead of the other take place in the brain of recovered aphasic patients. METHODS: Using blood oxygenation level-dependent functional MRI (fMRI), we studied cortical language networks during lexical-semantic processing tasks in 7 right-handed aphasic patients at least 5 months after the onset of left-hemisphere stroke and had regained substantial language functions since then. RESULTS: We found that in the recovered aphasic patient group, functional language activity significantly increased in the right hemisphere and nonsignificantly decreased in the left hemisphere compared with that in the normal group. Bilateral language networks resulted from partial restitution of damaged functions in the left hemisphere and activation of compensated (or recruited) areas in the right hemisphere. Failure to restore any language function in the left hemisphere led to predominantly right hemispheric networks in some individuals. However, better language recovery, at least for lexical-semantic processing, was observed in individuals who had bilateral rather than right hemisphere-predominant networks. CONCLUSIONS: The results indicate that the restoration of left-hemisphere language networks is associated with better recovery and inversely related to activity in the compensated or recruited areas of the right hemisphere.
Adult↗
HIV-1-specific immune responses in subjects who temporarily contain virus replication after discontinuation of highly active antiretroviral therapy.
Therapeutic intervention with highly active antiretroviral therapy (HAART) can lead to suppression of HIV-1 plasma viremia to undetectable levels for 3 or more years. However, adherence to complex drug regimens can prove problematic, and subjects may temporarily discontinue HAART for variable periods. We studied 6 HIV-1-infected individuals who stopped therapy. Off HAART, levels of viremia were suppressed to fewer than 500 copies/mL in 2 subjects for more than 12 and more than 24 months, respectively, and in 1 subject for 4 months on 1 occasion. Three subjects failed to contain plasma viremia. Broad and strong HIV-1-specific immune responses were detected in subjects with prolonged suppression of viral replication. This longitudinal study suggests that containment of HIV-1 replication to low or undetectable levels after discontinuation of HAART is associated with strong virus-specific immune responses. Boosting of HIV-1-specific immune responses should be considered as an adjunctive treatment strategy for HIV-1-infected individuals on HAART.
Acquired Immunodeficiency Syndrome↗
Model dependence of the phylogenetic inference: relationship among carnivores, Perissodactyls and cetartiodactyls as inferred from mitochondrial genome sequences.
Some previous analysis of mitochondrial proteins strongly support the Carnivora/Perissodactyla grouping excluding Cetartiodactyla (Artiodactyla + Cetacea) as an outgroup, but the support of the hypothesis remains equivocal from the analysis of several nuclear-encoded proteins. In order to evaluate the strength of the support by mitochondrial proteins, phylogenetic relationship among Carnivora, Perissodactyla, and Cetartiodactyla was estimated with the ML method by using the updated data set of the 12 mitochondrial proteins with several alternative models. The analyses demonstrate that the phylogenetic inference depends on the model used in the ML analysis; i.e., whether the site-heterogeneity is taken into account and whether the rate parameters are estimated for each individual proteins or for the concatenated sequences. Although the analysis of concatenated sequences strongly supports the Carnivora/Perissodactyla grouping, the total evaluation of the separate analyses of individual proteins, which approximates the data better than the concatenated analysis, gives only ambiguous results, and therefore it is concluded that more data are needed to resolve this trichotomy.
Animals↗
Therapeutic potentials of angiostatin in the treatment of cancer.
The discovery of specific endothelial inhibitors such as angiostatin and endostatin not only increases our understanding of the functions of these molecules in the regulation of physiological and pathological angiogenesis, but also provides an important therapeutic strategy for cancer treatment. Recent studies have demonstrated that the angiostatin protein significantly suppresses the growth of a variety of tumors in mice. However, the dosages of angiostatin protein used in these animal studies seem to be too high for clinical trials. In addition, repeated injections and long-term treatment with angiostatin are required to reach its maximal antitumor effect. In this article, I will discuss several alternative approaches that may become feasible to move angiostatin therapy from animal experiments into the clinic. In particular, I will emphasize the therapeutic potentials of angiostatin gene therapy and more potent angiogenesis inhibitors that are related to angiostatin.
Angiostatins↗
Development and usefulness of new polymerase chain reaction-based tests for detection of different alleles at codons 136 and 171 of the ovine prion protein gene.
OBJECTIVE: To develop new and improved tests to detect alleles at codons 136 and 171 of the ovine prion protein locus and to evaluate the frequency of these alleles. ANIMALS: 159 Suffolk sheep belonging to 3 flocks. PROCEDURE: Polymerase chain reaction (PCR) analysis that contained diagnostic restriction site variation for each allele were developed for the relevant gene regions. Alleles were determined by analyzing DNA isolated from buccal swab specimens or blood samples. RESULTS: At codon 136, frequencies of the alanine and valine alleles were found to be 97 and 3%, respectively. At codon 171, frequencies of the glutamine, arginine, and histidine alleles were found to be 57, 41, and 2%, respectively. CONCLUSIONS: Little variation was detected in codon 136, whereas noteworthy variation was found in codon 171; > 40% of the alleles at this locus coded for glutamine. Because the glutamine allele at codon 171 confers susceptibility to scrapie, reduction of its frequency is of importance to management of sheep flocks. CLINICAL RELEVANCE: Genotyping of sheep, using the tests reported here, should facilitate selective breeding programs designed to decrease the risk of scrapie.
Alleles↗
[Columbia University experience of detection of circulating cells by RT-PCR PSA in prostate cancer as a predictive factor of stage and biochemical recurrence].
OBJECTIVES: The Columbia University experience of RT-PCR PSA as a predictive factor of stage and biochemical recurrence is reviewed by trying to explain its differences. PATIENTS AND METHODS: 319 patients were included between January 1993 and March 1998. Radical prostatectomy was performed in all patients by the same surgeon. The RT-PCR protocol has been previously described (Katz et al., Urology, 1994). Biochemical recurrence was defined by a PSA greater than or equal to 0.2 ng/ml. RESULTS: Histological examination diagnosed 218 pT2 and 101 pT3 tumours. Thirty-four of the 218 pT2 patients (16%) had a positive RT-PCR versus 51 of the 101 pT3 patients (51%, p < 0.001). Analysis of Kaplan-Meier curves showed an 84% recurrence-free survival when RT-PER was negative versus 47% when RT-PCR was positive (Log-rank test, p = 0.0002). Multivariate analysis showed that independent predictive factors of biochemical recurrence were stage (p = 0.004), Gleason score estimated on the operative specimen (p = 0.010) and serum PSA (p = 0.047); RT-PCR (p = 0.075), strongly correlated with stage, was not an independent predictive factor. By exclusively comparing preoperative parameters, PSA (p = 0.004) and RT-PCR (p = 0.006) were found to be independent predictive factors compared to digital rectal examination (p = 0.371) and Gleason score on biopsies (p = 0.076). CONCLUSION: In this institution, RT-PCR PSA is a predictive parameter of stage and biochemical recurrence. No consensus has yet been reached in the literature concerning the reference protocol, as each team has developed its own RT-PCR technique applied to its own patient population. Comparison of results is therefore difficult.
Adult↗
A 12-Mb complete coverage BAC contig map in human chromosome 16p13.1-p11.2.
We have constructed a complete coverage BAC contig map that spans a 12-Mb genomic segment in the human chromosome 16p13.1-p11.2 region. The map consists of 68 previously mapped STSs and 289 BAC clones, 51 of which-corresponding to a total of 7.721 Mb of genomic DNA-have been sequenced, and provides a high resolution physical map of the region. Contigs were initially built based mainly on the analysis of STS contents and restriction fingerprint patterns of the clones. To close the gaps, probes derived from BAC clone ends were used to screen deeper BAC libraries. Clone end sequence data obtained from chromosome 16-specific BACs, as well as from public databases, were used for the identification of BACs that overlap with fully sequenced BACs by means of sequence match. This approach allowed precise alignment of clone overlaps in addition to restriction fingerprint comparison. A freehand contig drawing software tool was developed and used to manage the map data graphically and generate a real scale physical map. The map we present here is approximately 3.5 x deep and provides a minimal tiling path that covers the region in an array of contigous, overlapping BACs.
Base Sequence↗
[Cloning and expression analyses of down-regulated cDNA C6-2A in human esophageal cancer].
OBJECTIVE: To clone genes associated with the genesis of human esophageal cancer. METHODS: Identifying missing or low expressing cDNAs in human esophageal cancer tissues by mRNA differential display and examining its mRNA expression in 4 human cancer cell lines, 9 fetal tissues and other matched esophageal cancer tissues by Northern blot, dot blot and RT-PCR. RESULTS: One cDNA fragment named C6-2A, was cloned and sequenced. There was no identical sequence with C6-2A in BLASTN database; but in querying Genbank EST, the authors found that C6-2A was identical with ne27b03.s1NCI-CGAP-C03 humans sapiens cDNA clone IMAGE:898541 3' and zv30g07.rl Soares ovary tumor NbHOT homo sapiens cDNA clone 755196. 6/6 esophageal cancer tissues in Northern blot and 7/8 in dot blot did not or slightly express C6-2A. RT-PCR analysis showed that C6-2A was expressed much lower in 17/20 esophageal cancer tissues than adjacent microscopically normal mucosa, highly expressed in fetal esophageal mucosa, skin, cerebrum, placenta; moderately expressed in fetal stomach and liver, but not detected in fetal heart, small intestine and kidney. CONCLUSION: The high frequency of deletion of decreased expression of C6-2A in esophageal cell lines and human esophageal cancer tissues suggested that C6-2A might be involved in the carcinogenesis of esophagus.
Cloning, Molecular↗
Transdifferentiation of prostate cancer cells to a neuroendocrine cell phenotype in vitro and in vivo.
PURPOSE: To better understand the source of neuroendocrine cells associated with human prostate cancer progression, we studied the ability of a cultured prostate cancer cell line, LNCaP, to transdifferentiate into neuroendocrine-like cells in vitro and in vivo. MATERIALS AND METHODS: Cyclic AMP concentrations were measured in extracts of LNCaP cells cultured in the presence of normal or hormone-deficient medium (containing charcoal-stripped serum) with the use of an immunoassay. Quantitative RT-PCR procedures were used to determine whether hormone depletion affects TGF-beta2 mRNA expression. Western blotting procedures (for neuron specific enolase [NSE]) were used to determine whether TGF-beta2 supplementation or antibody neutralization might affect the ability of cultured LNCaP cells to transdifferentiate to neuroendocrine-like cells. Finally, tumors formed from LNCaP cells xenografted into male nude mice were evaluated for the presence of neuroendocrine cells (prior and subsequent to castration of the host mouse) using an immunohistochemical stain for chromogranin A. RESULTS: LNCaP cells cultured in a hormone-deficient medium have a mean 9-fold increase in cyclic AMP (p = 0.02) and a significant decline in the expression of TGF-beta2 mRNA when compared with cells grown in normal medium. Supplementation or depletion of TGF-beta2 did not affect the neuroendocrine conversion of LNCaP cells as assessed by NSE expression patterns. LNCaP tumors growing in castrated male nude mice were found to have significantly increased numbers of chromogranin A positive neuroendocrine cells (46/high powered field) when compared with tumors growing in intact male mice (3/high powered field) (p = 0.0038). CONCLUSIONS: Exposure of LNCaP cells to a hormone deficient medium drastically increased cyclic AMP production and this may identify the biochemical pathway through which hormone depletion induces a neuroendocrine conversion of prostate cancer cells. Hormone depletion also reduced TGF-beta2 mRNA expression and this finding was consistent with our inability to demonstrate any effect of TGF-beta2 on neuroendocrine conversion in vitro. Finally, our demonstration of increased neuroendocrine cells found in LNCaP tumors growing in castrated immunodeficient mice suggests that the neuroendocrine cells associated with advanced human prostate tumors in vivo, arise from prostate cancer cells through the transdifferentiation process.
Animals↗
[The correlation between integration of HBV X, S, Pre-S, C gene and the expression of oncogenes/tumor suppressor genes in primary hepatocellular carcinoma].
OBJECTIVE: To study the relation between the integration of HBV X, S, Pre-S and C genes and the expression of oncogenes/tumor suppressor genes in hepatocellular carcinoma(HCC). METHODS: To prepare the Dig-HBV probes with random priming method, to detect the existing status of HBV DNA and the integration rates of HBV X, S, Pre-S and C genes by Southern blot and dot blot hybridization, and to examine the expression of oncogenes and tumor suppressor genes by immunohistochemistry in HCC. RESULTS: The integration rates of HBV X, S, Pre-S and C genes in HCC were 87.5%(28/32), 62.5% (20/32), 62.5%(20/32) and 25.0%(8/32), respectively. The expression rates of p62myc, p21ras, p53 and p16 proteins were 81.2%(26/32), 50.0%(16/32), 43.8%(14/32), and 31.3(10/32), respectively. Statistical analysis showed that the expression of p62myc, p21ras and variant p53 proteins was obviously higher in HCC group with X gene than in free-X gene HCC group and that the expression of p62myc protein was obviously higher in HCC group with Pre-S gene than in free-Pre-S HCC group. CONCLUSION: The integration of HBV X or Pre-S gene with cellular chromosome can activate myc, ras oncogenes and inactivate the p53 tumor suppressor gene.
Carcinoma, Hepatocellular↗
[Study on the relationship between the history of abnormal pregnancy and TORCH infection in pregnant woman].
OBJECTIVE: To investigate the relationship between the history of abnormal pregnancy and the Toxoplasma(TOX), Other(OTH), Rubella virus(RUV), Cytomegalo virus(CMV), Herpes simplex virus-II (HSV-II) (TORCH) infections in pregnant woman. METHODS: Enzyme-Linked immunosorbent assay(ELISA) combined with polymerase chain reaction (PCR) technique were used to detect TORCH infection in pregnant women with histories of abnormal pregnancies(study group, n = 54) and normal pregnant women (control group, n = 54). The fetal cord blood samples were also detected. RESULTS: In study group, the rates of previous TORCH infection: CMV 46.29%, RUV 16.29%, TOX 16.67%, HSV-II 29.63%. The rates of active infection: CMV 57.40%, RUV 59.26%, TOX 38.89%, HSV-II 46.29%. The rates of recurrent infection: CMV 38.89%, RUV 38.89%, TOX 11.11%, HSV-II 22.22%. These three kinds of infection rates in study group were significantly higher than that of control group (P < 0.01). The abnormal pregnant cntcomes in study group were significantly higher than that of control group(P < 0.01). The incidence of maternal-fetal vertical transmission in study group was 73.08%. CONCLUSION: TORCH series infection is one of the important causes of abnormal pregnant cutcomes. It is absolutely necessary to screen TORCH infection for women who had the histories of abnormal pregnancies in order to prevent birth defects and perinatal complications. ELISA combined with PCR technique is a valuable method for the diagnosis of TORCH infection.
Adult↗