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Biomedical subjects

M Lu

Publications and source records attributed to M Lu.

At least 343 records · Page 19Linked to original sources

Drug binding by branched DNA: selective interaction of tetrapyridyl porphyrins with an immobile junction.

The differential binding of a number of water-soluble cationic porphyrins to a branched DNA molecule is reported. Tetrakis(4-N-methylpyridiniumyl)porphine (H2TMpyP-4) interacts near the branch point with an immobile DNA junction formed from four 16-mer strands. Its Cu(II) and Ni(II) derivatives show stronger preferential binding in the neighborhood of the branch point. Axially liganded derivatives, Zn, Co, and Mn, also interact near this branch point, but in a different way. We use the reagents methidiumpropyl-EDTA.Fe(II) [MPE.Fe(II)] and bis(o-phenanthroline)copper(I) [(OP)2Cu(I)] to cleave complexes of DNA duplex controls and the junction with these porphyrins. The resulting cleavage patterns are consistent with previous evidence that the branch point provides a strong site for intercalative binding agents, which is not available in unbranched duplexes of identical sequence. The preferential scission by (OP)2Cu(I) in the presence of Ni and Cu porphyrins near the branch point exceeds that seen for any agents we have studied. This hyperreactivity is not seen in the case of porphyrins with axial ligands, ZnTMpyP-4, CoTMpyP-4, and MnTMpyP-4, although these also interact near the branch point. The Zn derivative tends to protect sites close to the branch point from cutting, while the Co and Mn porphyrins moderately enhance cleavage of sites in this region.

Base Sequence↗

Structure of the human smooth muscle alpha-actin gene. Analysis of a cDNA and 5' upstream region.

The structures of a cDNA and the 5' upstream region of the human smooth muscle alpha-actin gene have been characterized. Transcriptional start sites and the non-coding first exon were mapped by primer extension analysis and by comparing cDNA and genomic sequences. The deduced human smooth muscle alpha-actin protein sequence is identical to the corresponding bovine protein sequence, and thus confirms that the previously determined human genomic sequence contained a mutation at codon 312. Human smooth muscle cells express only a single, 1.4-kilobase smooth muscle alpha-actin transcript. 5' Noncoding sequences that have the greatest similarity to the chicken gene are located in five noncontiguous segments, extending from approximately 250 base pairs upstream of the cap site through the first exon. Conserved sequences encompass a region required for expression and tissue-specific regulation of chicken smooth muscle alpha-actin and therefore are probably also important for expression of the human gene.

Actins↗

Drug binding by branched DNA molecules: analysis by chemical footprinting of intercalation into an immobile junction.

Branched DNA structures interact with drugs differently from unbranched control duplexes of similar sequence. A specific interaction between the reagent (methidiumpropyl-EDTA).Fe(II) [MPE.Fe(II)] and a branched DNA molecule formed from 16-mer oligonucleotide strands has been reported [Guo, Q., Seeman, N. C., & Kallenbach, N. R. (1989) Biochemistry 28, 2355-2359]. The structure of the branched molecule is thought to be made up of two double-helical stacking domains with an overall twofold symmetry across the branch site. The MPE-Fe(II) interaction occurs predominantly at or adjacent to the branch site and is eliminated by a second intercalator, propidium iodide. Further studies on the nature and properties of this site are presented here. Comparison of the patterns of scission of linear duplex and branched tetramer by EDTA.Fe(II), MPE.Fe(II), and Cu(I)-(o-phenanthroline)2 [(OP)2Cu(I)] provides a higher resolution picture of the site of enhanced binding. In particular, the sensitive footprinting afforded by (OP)2Cu(I) allows us to localize the major site of preferential interaction with propidium precisely to the branch point itself, with a roughly twofold symmetric pattern of cuts resulting. In detail, the differential pattern with respect to each duplex control is distinct for each arm of the junction. Excess propidium results in apparent reversal of the crossover isomer of the junction, indicating a possible additional avenue for the action of drugs in biological systems--effects on the products of recombination.

Base Sequence↗

Molecular characterization of the t(10;14) translocation breakpoints in T-cell acute lymphoblastic leukemia: further evidence for illegitimate physiological recombination.

The t(10;14)(q24;q11) translocation is a non-random chromosome change seen in the leukemic cells of 5-10% of patients with T-cell acute lymphoblastic leukemia (T-ALL). Recent studies support the hypothesis that the translocation occurs in the course of aberrant physiological recombination and results in the juxtaposition of a T-cell receptor (TCR) gene in 14q11 with a putative oncogene, TCL3, in 10q24. We cloned and sequenced the translocation breakpoints on both derivative 10q+ and 14q- chromosomes from a patient with t(10;14)(q24;q11) T-ALL. Two distinct diversity segments of TCRD, D delta 2 and D delta 3, were identified at the two translocation breakpoints on chromosome 14. The 9.5 kb DNA that separates these two subunits in the germline was deleted, possibly in the course of a D-D joining event. The two chromosome 10 breakpoints were 10 nucleotides apart and occurred in the immediate vicinity of a pseudo-heptamer signal motif. N-region addition is also evident at the breakpoint on the derivative chromosome 10. Our observations strongly suggest that the IG/TCR recombinase normally involved in V-(D)-J joining was involved in the process of the t(10;14)(q24;q11) translocation.

Base Sequence↗

Distribution of charged residues stabilizes individual helices in myoglobins.

The effect of the distribution of charged residues on stability of alpha helices in isolated peptides and in globular proteins exemplified by myoglobins from 62 different species is discussed. A highly simplified set of rules is used to account for the interaction of charged groups with the dipole of an alpha helix. Only the position and sign of a charge with respect to the center of the helix and its ability to participate in intrahelical salt bridges determine its effect. These rules lead to a linear correlation between the helicity in variant C-peptide helices from RNAse and the extent to which the charge distribution opposes the helix dipole. Of the sample of 496 helices in the myoglobins studied, 456 exhibit arrangements of charges which oppose the effective dipole moment of the helix according to this calculation. A number of variants occur which leave the backbone moment of helices A-D unchanged, or even add to it. However no such variants exist in the sequences of helices E-H. We suggest that the E, F, G and H helices in myoglobins which show the strongest reversal of the helix dipole participate in the structures of early intermediates in folding of the chain. Stable helix structures should be more likely to occur in these isolated sequences also, and introduction of charge alterations in helices E to H should affect the initial refolding rate of mutant myoglobins.

Amino Acid Sequence↗

Internalization of fluorescent vasotocin-receptor agonist and antagonist in the toad bladder.

This study compares hydrosmotic action, receptor binding, and fluorescent uptake of an agonist, d9phe(flu)AVT, and an antagonist, d4lys(flu)AVT, in the toad bladder. D9phe(flu)AVT increased osmotic water flow across the bladder with a 50% effective dose of 2 nM, whereas d4lys(flu)AVT inhibited water flow with a 50% effective dose of 0.1 microM. D9phe(flu)aVT displaced 10 nM [3H]arginine vasopressin (AVP) from plasma membranes by 50% (IC50) with 10 nM, whereas d4lys(flu)AVT had an IC50 of 3 microM. The fluorescent agonist induced a persistent increase in membrane permeability to water after removal from the serosal bathing solution. This residual response was diminished by preincubation with an agonist (AVP), but not with an antagonist [d4lys(N3)AVT]. The agonist, d9phe(flu)AVT, was internalized into toad bladder epithelial cells, as seen by epifluorescence microscopy, and this uptake was blocked by d4lys(N3)AVT. The antagonist, by contrast, was not internalized but remained at the cell surface. After stimulation with forskolin, however, the fluorescent antagonist was also internalized. These experiments suggest that agonists, but not antagonists, form functional complexes with receptors that, via formation of cAMP, trigger not only an increase in membrane permeability to water but also facilitate the clearance of hormone from the cell surface by endocytic uptake.

Animals↗

[Simultaneous determination of brucine and strychnine in semen Strychni by dual wavelength spectrophotometry and studies on processing principles of semen Strychni].

The paper reports the experimental result of the simultaneous quantitative determination of strychnine (ST) and brucine(BR) in Semen Strychni by dual wavelength spectrophotometry. The result shows that there are some deviations in the official method, because the wavelength combination might not have been chosen rightly and the correct coefficient is inconsistent with the facts. We have made a study of the thermal stability of ST and BR, too. On this basis a baking principle for Semen strychni is spelt out.

Drugs, Chinese Herbal↗

[Studies on the phenomenon of latent propagated sensation along channel (LPSC) by combining applied knocks, measurement of resistance and record electric current].

About twenty five percent of people have the typical phenomenon, i.e. a specific feeling propagating along the channel course during the application of needling or other stimuli on Jing acupoint. These characteristics are named marked PSC. About seventy five percent of people with no prominent propagated sensation. We concerned about how to change the obscure appearance into obvious. Combining applied knocks, measurement resistance and record electric current were used in our studies. RESULTS 1. After knocks, a specific propagational numb feeling at the point which is named as "positive point". 2. Most positive points of channel course on all of the 26 subjects under examination, the impedance value 40-65 (100 k omega) was lower than that at control points 80-90 (100 k omega), but the amplitude of electric current wave (14-38 cm) was higher than that at control points (6-11 cm). 3. By linking up these positive points of specific feeling an imaginary line which just the classical large intestine channel, this line is named as latent propagational sensation ling along channel (LPSC).

Acupuncture Points↗

DNase I cleavage of branched DNA molecules.

We report here a potentially useful signature of branched DNA structures. The base 5' to the branch and the five bases flanking the 3' side of the branch site are protected from cleavage by DNase I in both three- and four-arm branched DNA molecules. Our procedure is to measure the cleavage profile for each 5' -labeled strand in a control duplex and compare this with that of the same strand in a branched structure under conditions yielding less than one cut per strand. The resulting cleavage pattern in an immobile four-arm junction is roughly 2-fold symmetric, consistent with the pattern of Fe(II).EDTA-induced cleavage that has been observed previously. In the three-arm junction, the DNase I cleavage pattern is asymmetric, indicating lack of 3-fold symmetry. A variable pattern of protection occurs to the 5' side of the branch in some strands only for both three- and four-arm junctions, extending 2-4 residues 5' to the branch.

Base Sequence↗

An epidemiological survey of age-related dementia in an urban area of Beijing.

An epidemiological survey of age-related dementia among community residents of an urban of Beijing was conducted in 1986. Initial screening of 1331 subjects aged 60 and above was made using the Mini-Mental State Examination (MMSE) with a cutoff point of 17. All suspected cases of dementia and 5.5% of all others were then given a full clinical examination, with subjects being diagnosed and classified according to DSM-III criteria. The MMSE was found to have satisfactory sensitivity, although scores were significantly correlated with education. Prevalence rates of moderate and severe dementia were 1.28% for those aged 60 and above and 1.82% for those aged 65 and above. Rates for multi-infarct dementia were higher than those for primary degenerative dementia; females had higher rates than males and rates increased sharply with age. All the dementia cases were cared for in their own homes, by relatives. There is a need for increased knowledge and services for elderly people in the community.

Aged↗

[Morphometric study on sensitization by hematoporphyrin derivative in Ehrlich ascites tumor cells irradiated by gamma-ray].

In this paper, light and electron micrographs of Ehrlich ascites tumor cells radiated by gamma-ray and influenced by hematoporphyrin derivative (HPD) were analysed by morphometric method. It was found that in these cells, the domain of microfilaments treated by HPD expanded extensively, which enhanced the damage of cells induced by gamma-ray. Twenty five minutes after radiation, the cellular fragments increased, resulting in a decrease in the mean diameter of cells and an increase of nuclear volume density and nucleocytoplasmic ratio. In addition, ribosomes on the rough endoplasmic reticulum surfaces fell off increasingly and the quantity of smooth endoplasmic reticula increased.

Animals↗

Comparative study of the femoral articular facies of knees of the primates.

In this article, on the basis of the characteristics of the moiré contour fringes of Nycticebus coucany, Macaca assamensis M'clelland, Presbytis phayrei, Phinopithecus roxellanae, Hylobates concolor leucogenys, Gorilla gorilla. Anthropopithecus troglodytes. Simia satyrus and modern human beings we divide the Primates into two types. The two types of the new classification may be two groups of the evolution moving state. For comparison with each other, the angle gamma between the approximately elliptical major axis of the moiré contour fringes on the medial condyle and the horizontal plane is taken as the criterion. We suggest that the Primates evolution to the state of erect walking is the process of the angle gamma evolution approaching 90 degrees, regarding the gamma of the moiré contour fringes of the medial condyle as the evolution angle on the knees of the Primates.

Animals↗

Linkage studies of Friedreich ataxia by means of blood-group and protein markers.

Friedreich ataxia (FA) is an autosomal recessive, neuro-degenerative disorder in which the pathogenetic mechanism remains unidentified despite extensive biochemical studies. Genetic-linkage studies provide an alternative approach to determining the basic defect. Linkage analysis between FA and 36 polymorphic-blood-group and protein markers has been carried out on three separate patient populations--16 families from the inbred Acadian population of Louisiana, 21 French-Canadian families from Quebec, and nine apparently unrelated British families--in an attempt to determine the chromosomal location of the disease mutation. Neither evidence of linkage to any of the markers investigated nor heterogeneity among the populations was found for any of the comparisons. The negative lod scores exclude the locus for FA from greater than 20% of the genome.

Blood Group Antigens↗

A DNA deletion associated with multiple impaired transcripts in the visual mutant TRP.

The transient receptor potential (trp) mutant in Drosophila is known to manifest retinal degeneration and involves defects in the intermediate steps of visual transduction. The chromosome walking technique has been conducted at the cytogenetic location of trp. Overlapping phage clones that cover a DNA stretch of 73 kb were obtained. Southern blotting studies detected a 2.3 kb DNA deletion within this region in the mutant. The deleted DNA fragment contains exons of three transcripts with lengths of 3.5, 1.5 and 0.8 kb. The transcription of the 3.5 and 1.5 kb RNAs is completely abolished in the mutant, whereas that of 0.8 kb RNA appears to be modified. The impairment in production of three RNAs, due to the DNA deletion, offers a possible molecular basis of the multiple defects displayed by the trp- phenotype.

Animals↗

Double immunoenzymatic labeling of lymphomatous tissues for both immunologic phenotype and a malignancy-associated nucleolar antigen.

Defining cell lineage in the non-Hodgkin's lymphomas (NHL) is challenging for the immunopathologist. Cell surface marker techniques have made a major contribution to the understanding of the biology and classification of lymphoproliferative disorders by permitting the determination of the lymphoid (B- or T-cell) or monocytic lineage of the tumors. Because lymphoma cells often simulate the morphologic features and cell surface phenotype of their normal lymphocytic counterparts, it is difficult to discriminate normal from neoplastic lymphocytes. The authors have used representative monoclonal antibodies (MAb) to cell surface antigens to assess tumor cell surface antigens associated with various lymphoreticular cell lineages. Heteroantisera to the human malignancy-associated nucleolar antigen (HMNA) was utilized as a marker for neoplastic lymphoid cells as previously described. The use of double immunoenzymatic staining with both peroxidase and alkaline phosphatase allow us simultaneously to determine lymphoid lineage and malignancy on human lymphoma cells. In 101 cases of various cell types of NHL, the anti-HMNA antiserum reacted with nucleoli in the morphologically neoplastic lymphoma cells, but not with normal-appearing lymphoid and other cell types present in the lesions. Control specimens from normal and hyperplastic lymphoid tissue also failed to react with anti-HMNA antibodies.

Antibodies, Monoclonal↗