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Biomedical subjects

X Luo

Publications and source records attributed to X Luo.

At least 289 records · Page 16Linked to original sources

Charge densities of atoms of conjugated styryl ketones having activity against L1210 leukemia cells.

Electron density calculations were undertaken on several atoms in a series of 3-substituted-4-phenyl-3-buten-2-ones in order to gain insight into the molecular features which affect charge densities. The results indicate that substituents at position 3 alter the electron densities of the olefinic group but have little effect on the acetyl function. The compounds were tested against L1210 cells in vitro, and the results suggest that electronic--but not steric--factors are important in affecting cytotoxicity. The most active compound was 3-phenylmethylene-2,4-pentanedione (1c) with an ED50 value of 1.06 x 10(-8) M.

Animals↗

[A rapid FIA-spectrophotometric method with online extraction for the content uniformity test of atropine sulfate tablets].

A rapid spectrophotometric method based on FIA for the content uniformity test of atropine sulfate tablets has been developed. By means of the self-designed FIA system with an on-line extraction device, many difficulties resulting from extraction, such as slow analytical rate, environmental pollution, poor reproducibility, etc, were overcome, and the routine procedure of the official content uniformity test was tremendously simplified. Results obtained with the proposed method agree well with those obtained with the official test. Furthermore, the proposed method attained a sampling rate of 60 samples per hour, a recovery of 100.0%, a relative standard deviation of 0.7%, and a detection limit of 0.24 micrograms/ml. Uniform design proves effective to optimize complex FIA conditions, and FIA promises a new approach to test the content uniformity of pharmaceutical tablets.

Atropine↗

Role of reversible phosphorylation of acetyl-CoA carboxylase in long-chain fatty acid synthesis.

Acetyl-CoA carboxylase, the rate-limiting enzyme in the biogenesis of long-chain fatty acids, is regulated by phosphorylation and dephosphorylation. The major phosphorylation sites that affect carboxylase activity and the specific protein kinases responsible for phosphorylation of different sites have been identified. A form of acetyl-CoA carboxylase that is independent of citrate for activity occurs in vivo. This active form of carboxylase becomes citrate-dependent upon phosphorylation under conditions of reduced lipogenesis. Therefore, phosphorylation-dephosphorylation of acetyl-CoA carboxylase is the enzyme's primary short-term regulatory mechanism; this control mechanism together with cellular metabolites such as CoA, citrate, and palmitoyl-CoA serves to fine-tune the synthesis of long-chain fatty acids under different physiological conditions.

Acetyl-CoA Carboxylase↗

[Studies on eliminating the influence of random errors of analytical methods on the content uniformity test].

The conclusion drawn from the content uniformity test for a batch of solid dosage forms is influenced by the random error of the analytical method (random methodic error for short) used. Theoretically, the test by variables based on the statistical parameters of the sample has the merit of eliminating the influence of the random methodic error according to the principle of superposition of errors. In this paper, random methodic errors of some analytical methods were obtained by experiment and then used to eliminate the influence of random methodic errors on the content uniformity test by variables devised by us. Thus, the accuracy of the test is further improved.

Pharmaceutical Preparations↗

Effects of SOS and MucAB functions on reactivation and mutagenesis of M13 replicative form DNA bearing bulky lesions.

We have previously determined the specificity of -1 frameshifts induced by aflatoxin-B1-2,3-dichloride (AFB1C12) in phage M13 double-strand replicative form (RF) DNA. The system consists of: (i) in vitro adduction of RF DNA of BK8, a lacZ + 1 frameshift derivative of phage M13mp8; (ii) transfection into unirradiated or UV-irradiated bacterial host cells; (iii) scoring and sequencing of revertants (i.e., -1 frameshifts). The previous data had shown that induction of SOS functions enhanced mutagenesis. However, this increase in mutagenesis is not accompanied by enhanced survival in a majority of the strains tested. Here, we present evidence to show that the lack of SOS reactivation is a specific property of the RF DNA system rather than a specific property of the lesion. A model mechanism based on the replicative strategy of transfected RF DNA can account for these observations. In addition, we have calculated individual Weigle mutagenesis factors at 8 major mutagen induced sites reported previously. Analysis of these data indicates that, within a restricted subset of possible mutational events (i.e., -1 frameshifts), Weigle mutagenesis is affected by both the DNA sequence environment of the mutation site as well as the repair phenotype of the cell.

Aflatoxin B1↗

Mechanisms of mutagenesis by a bulky DNA lesion at the guanine N7 position.

In order to examine the mechanisms of mutagenesis by a bulky DNA lesion at the guanine N7 position, the replicative form DNA of phage M13AB28 (mp8 without the amber codons in phage genes) was modified in vitro with aflatoxin B1-2,3-dichloride and transfected into appropriate Escherichia coli cells. Forward mutations in the lacZ alpha-complementing gene segment were identified as light blue or colorless plaques on appropriate indicator plates, isolated, and defined by DNA sequencing. Transfection of modified DNA into uvrA-/mucAB+ cells without prior UV (SOS) induction increased mutation frequency eight-fold over untreated DNA, whereas this increase was 12-fold upon SOS induction. Transfection of modified DNA after conversion of the primary guanine-aflatoxin lesions to the stable imidazole ring-opened formamidopyrimidine-aflatoxin suggested that these lesions were nearly equally mutagenic. A majority of point mutations under all conditions affected G:C bp. Base substitutions were in the majority, but significant frameshift mutagenesis was also detected in SOS-induced cells. Both G-to-T transversions and G-to-A transitions were produced at equal efficiency and together accounted for virtually all of the base substitutions induced by the primary lesions. Point mutations occurred predominantly at predicted damage hotspots. The characteristics of base substitution and frameshift mutations, together with available information point to multiple mechanisms of mutagenesis by this class of mutagens. The data indicate that primary lesions have the properties of both a noninstructional and pseudo-instructional lesion. In addition, the sequence context appears to play a role in determining whether a frameshift or a base substitution is induced by this bulky lesion.

Aflatoxin B1↗

[Cytogenetic studies on 3 esophageal cancer cell lines].

The cytogenetic studies on three esophageal cancer cell lines established in China were done. Thirty metaphases showing suitable chromosome length and good G-banding pattern from each of the cell lines were chosen and subjected to karyological analysis. The typical karyotypes from these cell lines were listed, and the variation of chromosome number as well as the morphological characteristics, possible sources and the incidence of the marker chromosomes were analysed. Eca 109 is the cell line first established and used extensively in China. A strictly regular karyotype pattern was found in it: the modal number of chromosomes being 63-64; the number of each type of chromosome varying between 1-5; a distal deletion of short arm of chromosome No. 1 being discernible in all metaphases, with break sites located within 1p22-1p33. Also a distal deletion of long arm of chromosome No. 4 was usually visible. There were seven marker chromosomes with high incidence. Among them, M1 marker chromosome was a large subacrocentric chromosome which was observed in the early passages of this cell line. The chromosome number of Ec 17 cell line was usually subtetraploid. In addition to the numerical variation in some of the chromosomes, six marker chromosomes were usually observed. Among them, M1 involved reciprocal translocation between chromosome No. 1 and No. 4. M3 of Ec 17 was in correspondence with M5 of Eca 109. Both were Rob (13q;14q). The chromosome number of Ec 56 was usually subtetraploid, and in addition to the numerical variation in some of the chromosomes, seven marker chromosomes were usually observed.

Cell Line↗

Malignant transformation of baby hamster lung fibroblasts induced in vitro by a new nitrosamine compound.

A new nitrosamine compound, N-1-methylacetonyl-N-3-methylbutyl-nitrosamine (MAMB-NA), isolated from corn bread inoculated with moulds commonly occurring in Linxian County, a high incidence area for esophageal cancer in North China was tested for its potential carcinogenicity in vitro. Baby hamster lung fibroblasts (BHL) were treated with MAMBNA in tissue culture medium containing liver microsome preparation of Aroclor 1254 treated rat. Cell transformation was assessed by morphological changes, loss of density-dependent inhibition and unlimited growth in vitro, chromosome changes, colony formation on soft agar, growth at low serum concentration, Con A agglutinability and tumor formation after heterotransplantation into immunosuppressed newborn rats. Like the known carcinogens N-methyl-N'-nitro-N-nitroso-guanidine and diethylnitrosamine, MAMBNA was able to cause malignant transformation of cells cultured in vitro.

Animals↗

Steroidogenic factor 1 (SF-1) is essential for endocrine development and function.

Steroidogenic factor 1 (SF-1), an orphan nuclear receptor, initially was isolated as a key regulator of the tissue-specific expression of the cytochrome P450 steroid hydroxylases. Thereafter, analyses of sites of SF-1 expression during mouse embryological development hinted at considerably expanded roles for SF-1, roles that were strikingly confirmed through the analyses of SF-1 knockout mice. These SF-1 knockout mice exhibited adrenal and gonadal agenesis, associated with male-to-female sex reversal of their internal and external genitalia and death from adrenocortical insufficiency. These findings showed unequivocally that SF-1 is essential for the embryonic survival of the primary steroidogenic organs. SF-1 knockout mice also had impaired pituitary expression of gonadotropins and agenesis of the ventromedial hypothalamic nucleus (VMH), establishing that SF-1 regulates reproductive function at all three levels of the hypothalamic-pituitary gonadal axis. This article reviews the experiments that have defined these essential roles of SF-1 in endocrine development and highlights important areas for future studies.

Animals↗

Analysis of two types of cone bipolar cells in the retina of a New World monkey, the marmoset, Callithrix jacchus.

Two types of cone bipolar cells, the blue cone bipolar cell and the diffuse bipolar cell (DB3), were labelled immunohistochemically and investigated in the retina of a New World monkey, the marmoset. Blue cone bipolar cells were labelled with an antiserum against cholecystokinin. Short-wavelength-sensitive (SWS) cones were labelled with an antiserum against the SWS cone opsin. The DB3 cells were labelled with antibodies to calbindin. Blue cone bipolar cells in marmoset do not form a regular mosaic but instead follow the random distribution of the SWS cones. Nevertheless, the SWS cone to blue cone bipolar cell connectivity in marmoset is very similar to that previously described for macaque. In contrast to the blue cone bipolar cells, the DB3 cells form a regular mosaic. The synaptic connectivity of DB3 cells in the inner plexiform layer was analyzed. They make output synapses onto ganglion cells and amacrine cells, and gap junctions with each other. Our results provide further evidence for the existence of parallel bipolar cell pathways in the primate retina and support the view that the retinae of Old World and New World primates have common neuronal connectivity. The random distribution of SWS cones and blue cone bipolar cells is an exception to the general rule of a regular mosaic distribution of cell populations in the retina.

Animals↗

A single carbocyclic nucleotide substitution in a 12mer DNA gives a Hoogsteen basepaired duplex (till 38 degrees C) and a hairpin (till 65 degrees C). A 600 MHz NMR spectroscopic study.

The impact of intramolecular stereoelectronic effects has been examined by comparison of the solution structures of natural oligo-DNA duplex, 5'(1C2G3C4G5A6A7T8T9C10G11C12G)2(3'), and its carbocyclic-nucleotide analogues in which the pentose sugar in 2'-dA residue is replaced with its carbocyclic counterpart (i.e. 2'-deoxyaristeromycin). Based on the NMR evidences, it has been shown, that 2'-deoxyaristeromycin analog exists in a dynamic equilibrium between the two forms of duplexes, one with W-C bp and the second with Hoogsteen bp in ca 1:1 ratio at lower temperature (below 35 degrees C) and as hairpin at higher temperature (from approximately 40 degrees-60 degrees C).

Base Pairing↗

A phase II trial of high-dose methotrexate in previously untreated children and adolescents with high-risk unresectable or metastatic rhabdomyosarcoma.

PURPOSE: The outcome for children with advanced-stage rhabdomyosarcoma remains poor with contemporary treatment regimens. Evaluation of new drugs is important to improve clinical outcome. Because methotrexate has shown promising activity in the treatment of patients with recurrent rhabdomyosarcoma, we conducted a phase II trial in untreated children with advanced-stage disease to evaluate the efficacy and safety of this agent. PATIENTS AND METHODS: Fifteen patients received 1 to 4 courses of high-dose methotrexate (HDMTX, 12 g/m2). Patients then received standard multiagent chemotherapy (vincristine, dactinomycin, cyclophosphamide, ifosfamide, mesna) with cytokine support and local radiotherapy. Patients who responded to HDMTX received four additional courses of this drug during continuation therapy. RESULTS: Twelve patients were evaluable for response after 2 or more courses of HDMTX; 4 achieved a partial response (33.3%). After administration of standard chemotherapy and radiation, the estimated 2-year progression-free survival for all patients was 56% (SD 15%). The drug was well-tolerated and the most common side effects included mucositis, transient elevation of transaminases, and neutropenia. The four patients who received additional courses of HDMTX during continuation therapy had limited toxicity which included mucositis, anemia, and thrombocytopenia. CONCLUSIONS: About one-third of children with previously untreated advanced-stage rhabdomyosarcoma responded to HDMTX. Its different mechanism of action and non-overlapping toxicity with other agents make HDMTX an attractive candidate for incorporation into front-line treatment regimens for rhabdomyosarcoma.

Adolescent↗