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B Mao

Publications and source records attributed to B Mao.

At least 55 records · Page 3Linked to original sources
PubMed1997

Solution structure of the aminofluorene-intercalated conformer of the syn [AF]-C8-dG adduct opposite a--2 deletion site in the NarI hot spot sequence context.

This paper addresses structural issues related to the capacity of aminofluorene [AF] for frameshift mutations of the -2 type on C8 covalent adduct formation at the G3 site in the d(C-G1-G2-C-G3-C-C) NarI hot spot sequence. This problem has been approached from a combined NMR and relaxation matrix analysis computational structural study of the [AF]dG adduct in the d(C-G-G-C-[AF]G-C-C).d(G-G-C-C-G) sequence context at the 12/10-mer adduct level (designated [AF]dG.del(-2) 12/10-mer). The proton spectra of this system are of exceptional quality and are consistent with the formation of an AF-intercalated conformer with the modified guanine in a syn alignment displaced along with the 5'-flanking cytosine residue into the major groove. The solution structure has been determined by initially incorporating intramolecular and intermolecular proton-proton distances defined by lower and upper bound deduced from NOESY spectra as restraints in molecular mechanics computations in torsion angle space and subsequently refined through restrainted molecular dynamics calculations based on a NOE distance and intensity refinement protocol. Strikingly, the [AF]dG.del(-2) 12/10-mer duplex adopts only one of two potential AF-intercalation alignments for the [AF]dG adduct opposite the -2 deletion site in the NarI sequence context with the extrusion of the dC-[AF]dG step favored completely over extrusion of the [AF]dG-dC step at the lesion site. This polarity establishes that the structural perturbation extends 5' rather than 3' to the [AF]dG lesion site in the adduct duplex. This structure of the [AF]dG adduct opposite a -2 deletion site shows distinct differences with conclusions reported on the alignment of the related acetylaminofluorene [AAF]dG adduct opposite a -2 deletion site in the identical NarI sequence context [Milhe, C., Fuchs, R. P. P., and Lefevre, J. F. (1996) Eur. J. Biochem. 235, 120-127]. In that study, qualitative NMR data without computational analysis were employed to conclude that the extrusion at the lesion site occurs at the [AAF]dG-dC step for the AAF-intercalated conformer of the adduct duplex. The structure of the [AF]dG adduct opposite a -2 deletion site determined in our group provides molecular insights into the architecture of extended slipped mutagenic intermediates involving aromatic amine intercalation and base-displaced syn modified guanines in AF and, by analogy, AAF-induced mutagenesis in the NarI hot spot sequence context.

Acetoxyacetylaminofluorene↗
PubMed1997

Solution structure of the aminofluorene-stacked conformer of the syn [AF]-C8-dG adduct positioned at a template-primer junction.

A solution structural study has been undertaken on the aminofluorene-C8-dG ([AF]dG) adduct located at a single strand-double strand d(A1-A2-C3-[AF]G4-C5-T6-A7-C8-C9-A10-T11-C12-C13).d (G14-G15-A16-T17-G18-G19-T20-A 21-G22) 13/9-mer junction (designated [AF]dG 13/9-mer) using proton-proton distance and intensity restraints derived from NMR data in combination with a computational protocol, which includes intensity refinement. This single strand-double strand junction models one arm of a replication fork composed of a 13-mer template strand, which contains the [AF]dG modification site, and a 9-mer primer strand, which has been elongated up to, but not including, the modified guanine. The NMR data establish that the duplex segment retains a minimally perturbed B-DNA conformation including Watson-Crick hydrogen-bonding at the junctional dC5.dG22 base pair. The NMR spectra are consistent with the guanine ring of the [AF]dG4 adduct adopting a syn glycosidic torsion angle and being displaced into the major groove with the adjacent dC3 residue displaced into the minor groove. Such a base displacement of the modified guanine is accompanied by stacking of one face of the fluorene ring of [AF]dG4 with the dC5.dG22 base pair, while the other face of the flourene ring is stacked with the purine ring of the nonadjacent dA2 residue in the intensity-refined solution structures of the [AF]dG 13/9-mer. A comparison of structural features of the C8-[AF]dG adduct (this study) with those of the (+)-trans-anti-N2-[BP]dG adduct [Cosman et al. (1995) Biochemistry 34, 15334-15350] in the same 13/9-mer junctional sequence context has identified common features associated with the alignment of the modified guanine adducts at the template-primer junction. Thus, despite differences in the covalent linkage site for the C8-[AF]dG and (+)-trans-anti-N2-[BP]dG adducts, one face of the aromatic ring of the carcinogen stacks over the junctional base pair and in so doing displaces the modified guanine in a syn alignment into the major groove. These results lend credence to earlier proposals that such an adduct alignment may represent a common mutagenic conformer at a template-primer junction associated with a replication fork.

Acetoxyacetylaminofluorene↗
PubMed1997

Single-strand breaks in oligodeoxyribonucleotides induced by fission neutrons and gamma radiation and measured by gel electrophoresis: protective effects of aminothiols.

The technique of high-resolution gel electrophoresis using oligodeoxyribonucleotides of known composition as model systems, offers a simple quantitative estimate of DNA damage in aqueous solution induced by ionizing radiation. The fraction of damaged DNA can be quantitatively defined in terms of the increased electrophoretic mobilities of the damaged oligonucleotides, relative to the mobility of the unirradiated and intact oligonucleotides. The usual direct strand breaks can be observed at gamma-ray dosages of 200 Gy. However, at a gamma-ray dosage of 400 Gy, only a broad background, attributed to heterogeneously and multiply damaged oligonucleotide fragments with overlapping and varying electrophoretic mobilities, can be distinguished. On the other hand, individual bands due to resolvable DNA fragments are evident even at dosages as high as 400 Gy for fission neutrons. When double-stranded oligonucleotides are exposed to gamma-ray dosages of 200 Gy, the fraction of damaged DNA approaches 30-40%. This damage can be almost completely suppressed (> 99%) if the irradiations are conducted in aqueous solutions in the presence of 0.5-1.0 mM concentrations of the thiols cysteamine or 3-(3-methylaminopropylamino)propanethiol (WR-151326). The rate constant of reaction of OH radicals with small double stranded oligonucleotides 16 base pairs long, KDNA, is found to be closer to the diffusion-controlled value (> 3 x 10(9) M-1 s-1) than the magnitudes of KDNA for the higher molecular weight, native DNA reported in the literature. These observations suggest that oligonucleotides represent more simple model systems than native DNA in solutions for studying the mechanisms of radioprotection exerted by thiols of different structures.

Amino Acids↗
PubMed1997

[Progress of study on biomechanical mechanisms of head impact injury].

This article reviews the researches on biomechanical mechanisms of head impact injury. Biomechanical factors that contribute to craniocerebral impact injury are discussed. The processes of injuries to skull and brain are described respectively. The contents include the static anatomic structure and dynamic properties of the skull, the changes of shear force and stress in skull fracture. The mechanisms of brain injury by linear movement and rotational movement as well as the relationship between skull injury and brain injury are described and analysed. Also the existing problems and the prospects for further research are brought forth.

Animals↗
PubMed1996

Solution conformation of the N-(deoxyguanosin-8-yl)-1-aminopyrene ([AP]dG) adduct opposite dC in a DNA duplex.

Combined NMR-molecular mechanics computational studies were undertaken on the C8-deoxyguanosine adduct formed by the carcinogen 1-nitropyrene embedded in the d(C5-[AP]G6-C7).d(G16-C17-G18) sequence context in a 11-mer duplex, with dC opposite the modified deoxyguanosine. The exchangeable and nonexchangeable protons of the aminopyrene moiety and the nucleic acid were assigned following analysis of two-dimensional NMR data sets in H2O and D2O solution. There was a general broadening of several proton resonances for the three nucleotide d(G16-C17-G18) segment positioned opposite the [AP]dG6 lesion site resulting in weaker NOEs involving these protons in the adduct duplex. The solution conformation of the [AP]dG.dC 11-mer duplex has been determined by incorporating intramolecular and intermolecular proton-proton distances defined by upper and lower bounds deduced from NOESY spectra as restraints in molecular mechanics computations in torsion angle space. The aminopyrene ring of [AP]dG6 is intercalated into the DNA helix between intact Watson-Crick dC5.dG18 and dC7.dG16 base pairs. The modified deoxyguanosine ring of [AP]dG6 is displaced into the major groove and stacks with the major groove edge of dC5 in the adduct duplex. Both carbon and proton chemical shift data for the sugar resonances of the modified deoxyguanosine residue are consistent with a syn glycosidic torsion angle for the [AP]dG6 residue. The dC17 base on the partner strand is displaced from the center of the helix toward the major groove as a consequence of the aminopyrene ring intercalation into the helix. This base-displaced intercalative structure of the [AP]dG.dC 11-mer duplex exhibits several unusually shifted proton resonances which can be accounted for by the ring current contributions of the deoxyguanosinyl and pyrenyl rings of the [AP]dG6 adduct. In summary, intercalation of the aminopyrene moiety is accompanied by displacement of both [AP]dG6 and the partner dC17 into the major groove in the [AP]dG.dC 11-mer duplex.

Base Composition↗
PubMed1996

Structure and function of the band 3 Cl-/HCO3- transporter in chronic respiratory failure patients.

OBJECTIVE: To study red blood cell (RBC) membrane band 3 protein structure and anion transport function in cor pulmonale patients with respiratory failure. PATIENTS AND METHODS: Blood samples were obtained from 80 cases of cor pulmonale and 37 normal subjects (control group). The patients were divided into type I respiratory failure (Group I, n = 40) and type II respiratory failure (Group II, n = 40). The anion permeability of the erythrocyte membrane (Pcl), PO2 and PCO2 in 12 of the patients with type II respiratory failure were observed in acute stage (AS), chronic stage (CS) and recovery stage (RS). Membrane protein was analyzed by polyacrylamide electrophoresis in SDS. 55-KDa membrane domain was fractionated on 10% NaDodSO4 polyacrylamide gel column and purified further with a sephadax G-25 column. The composition of amino acids was analyzed on a Beckman 6300 Gold system amino acid analyzer. The Pcl was determined by the hypoisotonic hemolysis method. RESULTS: The relative content of band 3 protein erythrocytic membrane, anion permeability coefficient of the erythrocyte membrane and plasma chloride in the patients with cor pulmonale with type II respiratory failure were significantly lower than those in the patients with type I respiratory failure and the control. The number of residues in the anion transport domain of the trypsin fragment of 55,000 daltons of band 3 protein showed no significant difference among the three groups. CONCLUSIONS: The structure of anion transport sites remains intact and so the reduction of the anion transport function of band 3 protein in patients with cor pulmonale with type II respiratory failure may be due to the decrease of the relative content of band 3 protein, the decrease of extraerythrocytic chloride and hypoxia.

Anion Exchange Protein 1, Erythrocyte↗
PubMed1996

[Clinical analysis of diffuse axonal injury].

Sixty cases of diffuse axonal injury were analysed in this paper. All cases were caused by traffic accident; the mortality was 53.12%. Clinical manifestations were post-traumatic immediate and continuous coma with severe dysfunction of brain stem. MRI is helpful for clinical diagnosis. Pathological findings include the diffuse axonal injury of cortical while matter, corpus callosum, brain stem, and focal hemorrhage and infarction. The early use of hyperbaric oxygen combined with neuro-growth factor as an effective therapy is recommended.

Accidents, Traffic↗
PubMed1996

[Medulloblastoma of posterior fossa in children--report of 42 cases].

Forty-two cases of medulloblastoma of posterior fossa in children are presented in this paper. Of the children, 28 were males and 14 females; their age ranged from 1.5 to 12 (mean 7.3) years. The foci found were in vermis (36) and cerebellar hemispheres (6). All of these children presented symptoms and signs of obviously increased intracranial pressure, and 31(77%) of them had the signs of cerebellar functional deficits. CT scan showed severe obstructive hydrocephalus in 39 cases. 42 children with posterior fossa medulloblastoma underwent surgical resection. Three died of postoperative prespiratory and circulatory failure, 39 made good recovery and received craniospinal radiotherapy and adjunct chemotherapy. Up to now, none died. Surgical intervention and operative procedures were emphasized particularly. Radiotherapy and chemotherapy were discussed also.

Child↗
PubMed1995

Solution conformation of [AF]dG opposite a -2 deletion site in a DNA duplex: intercalation of the covalently attached aminofluorene ring into the helix with base displacement of the C8-modified syn guanine and adjacent unpaired 3'-adenine into the major groove.

This paper reports the solution conformation of the covalent aminofluorene-C8-deoxyguanosine [AF]dG adduct positioned opposite a -2 deletion site in a DNA oligomer duplex. The combined NMR and molecular mechanics computational studies were undertaken on the [AF]dG adduct embedded in the d(C5-[AF]G6-A7-C8).d(G17-G18) sequence context in a duplex containing 12 residues on the modified strand and 10 on the partner strand, with no bases opposite the [AF]dG6-dA7 segment. The exchangeable and nonexchangeable protons of the aminofluorene moiety and the nucleic acid were assigned following analysis of two-dimensional NMR data sets in H2O and D2O solution. The solution conformation of the [AF]dG.2del 12-mer duplex has been determined by incorporating intramolecular and intermolecular proton-proton distances defined by upper and lower bounds deduced from NOESY spectra as restraints in molecular mechanics computations in torsion angle space. The aminofluorene ring of [AF]dG6 is intercalated between intact Waston-Crick dC5.dG18 and dC8.dG17 base pairs with the deoxyguanosine base of [AF]dG6 in a syn alignment displaced into the major groove. The syn glycosidic torsion angle at [AF]dG6 is supported by both carbon and proton chemical shift data for the sugar resonances of the modified deoxyguanosine residue. The unpaired dA7 base is also looped out of the helix into the major groove with the purine rings of [AF]dG6 and dA7 stacking on each other in the groove. The long axis of the intercalated aminofluorene ring is parallel to the long axis of the flanking dG.dC base pairs. The intercalation site is wedge shaped with a pronounced propeller-twisting and buckling of the dC5.dG18 base pair. The deoxyguanosine base of [AF]dG6, which is positioned in the major groove, is inclined relative to the helix axis and stacks over the 5'-flanking dC5 residue in the solution structure. The intercalative base displacement structure of the [AF]dG.2del 12-mer duplex exhibits several unusually shifted proton resonances that can be readily accounted for by the ring current contributions of the deoxyguanosine purine and carcinogen fluorene aromatic rings of the [AF]dG6 adduct. We note similarities between the present conformation of [AF]dG positioned opposite a -2 deletion site with our earlier conformational studies of [AF]dG positioned opposite a -1 deletion site [Mao, B., Cosman, M., Hingerty, B. E., Broyde, S., & Patel, D. J. (1995) Biochemistry 34, 6226-6238]. For both conformations, the aminofluorene carcinogen inserts into the helix at the deletion site through base displacement of the modified deoxyguanosine in a syn alignment into the major groove and directed toward its 5'-neighbor in the sequence. These structures provide a molecular explanation of how transient strand slippage of the lesion-containing segment can be accommodated by a double helix following translesion synthesis.

Base Sequence↗
PubMed1995

Stereochemistry-dependent bending in oligonucleotide duplexes induced by site-specific covalent benzo[a]pyrene diol epoxide-guanine lesions.

The apparent persistence length of enzymatically linearized pIBI30 plasmid DNA molecules approximately 2300 bp long, as measured by a hydrodynamic linear flow dichroism method, is markedly decreased after covalent binding of the highly tumorigenic benzo[a]pyrene metabolite 7R,8S-dihydroxy-9S,10R-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene [(+)-anti-BPDE]. In striking contrast, the binding of the non-tumorigenic, mirror-image 7S,8R,9R,10S enantiomer [(-)-anti-BPDE] to DNA has no measurable effect on its alignment in hydrodynamic flow gradients (< or = 2.2% of the DNA bases modified). In order to relate this effect to BPDE-nucleotide lesions of defined stereochemistry, the bending induced by site-specifically placed and stereochemically defined (+)- and (-)-anti-BPDE-N2-dG lesions in an 11mer deoxyoligonucleotide duplex was studied by ligation and gel electrophoresis methods. Out of the four stereochemically isomeric anti-BPDE-N2-deoxyguanosyl (dG) adducts with either (+)-trans, (-)-trans, (+)-cis, and (-)-cis adduct stereochemistry, only the (+)-trans adduct gives rise to prominent bends or flexible hinge joints in the modified oligonucleotide duplexes. Since both anti-BPDE enantiomers are known to bind preferentially to dG (> or = 85%), these observations can account for the differences in persistence lengths of DNA modified with either (+)-anti-BPDE or the chiral (-)-anti-BPDE isomer.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1995

Solution conformation of [AF]dG opposite a -1 deletion site in a DNA duplex: intercalation of the covalently attached aminofluorene ring into the helix with base displacement of the C8-modified Syn guanine into the major groove.

This paper reports on the solution structure of the [AF]dG adduct positioned opposite a deletion site in a DNA oligomer duplex that defines the alignment of the covalent aminofluorene--C8-guanine adduct relative to the deletion site. The combined NMR molecular mechanics computational studies were undertaken on the [AF]dG adduct embedded in the d(C5-[AF]G6-C7).d(G16-G17) sequence context in a duplex containing 11 residues on the modified strand and 10 on the partner, with no base opposite the modification. The exchangeable and nonexchangeable protons of the aminofluorene moiety and the nucleic acid were assigned following analysis of two-dimensional NMR data sets in H2O and D2O solution. The solution conformation of the [AF]G.del 11-mer duplex has been determined by incorporating intramolecular and intermolecular proton-proton distances defined by lower and upper bounds deduced from NOESY spectra as restraints in molecular mechanics computations in torsion angle space. The aminofluorene ring of [AF]dG6 is intercalated between intact Watson-Crick dC5.dG17 and dC7.dG16 base pairs with the guanine base of [AF]dG6 in a syn alignment displaced into the major groove. The syn glycosidic torsion angle at [AF]dG6 is supported by both carbon and proton chemical shift data for the sugar resonances of the modified guanine residue. The long axis of the aminofluorene ring is parallel to the long axis of the flanking dG.dC base pairs with the AF ring undergoing rapid 180 degrees flips on the NMR time scale. The intercalation site is wedge shaped with a pronounced propeller-twisting and buckling of the dC5.dG17 base pair. The guanine base of [AF]dG6, which is positioned in the major groove, is inclined relative to the helix axis and stacks over the 5'-flanking dC5 residue in the solution structure. The intercalative-base displacement structure of the [AF]dG.del 11-mer duplex exhibits several unusually shifted proton resonances that can be readily accounted for by the ring current contributions of the guanine purine and carcinogen fluorene aromatic rings of the [AF]dG6 adduct. There are similarities between this structure of the AF-C8-dG covalent adduct positioned opposite a deletion site and the (+)-trans-anti-BP-N2-dG covalent adduct positioned opposite a deletion site in the same sequence context reported previously from this laboratory [Cosman et al. (1994) Biochemistry 33, 11507-11517]. The chromophores are intercalated into the helix opposite the deletion site with displacement of the modified guanine into the major groove in both cases.(ABSTRACT TRUNCATED AT 400 WORDS)

Base Sequence↗
PubMed1995

Synthesis and characterization of covalent adducts derived from the binding of benzo[a]pyrene diol expoxide to a -GGG- sequence in a deoxyoligonucleotide.

Direct synthesis and purification procedures are described for the preparation of adducts derived from the covalent binding of 7R,8S-dihydroxy-9S,10R-epoxy-7,8,9,10-tetrahydro-benzo[a]pyrene [(+)-anti-BPDE or (+)-BPDE 2] to each of the three guanine residues (trans-N2-dG lesions) in the oligodeoxyribonucleotide d(CTATG1G2G3TATC). The positions of the modified Gs are defined by Maxam-Gilbert sequencing techniques. Six different oligonucleotides with one or two precisely positioned (+)-anti-BPDE residues are identified. The absorbance, circular dichroism and fluorescence characteristics are changed upon formation of duplexes with the complementary strands d(GATACCCATAG). In the doubly-modified oligonucleotides, a broad, excimer-like long wavelength fluorescence emission band is observed with a maximum near 455 nm only if the two (+)-anti-BPDE-modified Gs are adjacent to one another. The covalently attached (+)-anti-BPDE residues decrease the thermodynamic stabilities of the duplexes; their melting points are markedly dependent on the position of the lesions, being highest with the (+)-anti-BPDE residue at G1 (Tm = 40 degrees C, only 2 degrees C lower than in the case of the unmodified oligonucleotide) and lowest when it is situated at G3 (Tm = 29 degrees C). The implications of these and other physical characteristics are discussed. The facile synthesis of these or similar site-specific and stereochemically defined (+)-trans-anti-BPDE-N2-dG lesions in runs of contiguous guanines in oligodeoxyribonucleotides of specified base sequence should be useful for the design of site-directed mutagenesis studies in vitro and in vivo.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1995

[The value of serum myelin basic protein in assessment of severity of acute closed head trauma].

Serum levels of myelin basic protein (MBP) were measured in 112 patients after acute head injury by enzyme linked immuno-absorbent assay (ELISA). Patients with cerebral concussion showed no significant change in serum MBP. Patients with cerebral contusion, extradural hematoma or intracerebral hematoma had a mean serum MBP concentration much higher than that of patients with cerebral concussion. And patients with extradural hematoma had a mean serum MBP concentration much lower than that of patients with cerebral contusion and intracerebral hematoma; the differences were significant (P < 0.05). But there was no significant difference between patients with cerebral contusion and intracerebral hematoma (P > 0.05). The amount of serum MBP was significantly correlated with the volume of extradural hematoma, intracerebral hematoma and with the extent of the cerebral contusion (P < 0.05). This study suggested that the serum MBP may reflect the type and severity of closed head injury patients.

Adolescent↗
PubMed1995

[Myelin basic protein level in serum of patients with chronic cor pulmonale in acute phase].

With a sensitive enzyme-linked immunoadsorbent assay that can detect as little as 0.5ng/ml of myelin basic protein (MBP), we studied serum specimens from 34 patients with chronic cor pulmonale (CP) and 33 patients with chronic bronchitis (CB) during acute attack in hospital and 30 control subjects. The results showed that the serum mean MBP level of CP patients was markedly higher than those of CB patients and controls (P < 0.01), but no statistically significant differences were found between CB patients and controls (P > 0.05). There was a positive correlation between elevated levels of serum MBP and carbon dioxide partial pressure (PaCO2). This suggested that elevated serum MBP levels may be associated with brain destruction by hypercapnia and hypoxia of CP patients.

Acute-Phase Reaction↗
PubMed1995

[A study on erythrocyte membrane band 3 protein anion transport function in chronic respiratory failure patients].

The changes of the structure, content and anion transport function as well as the blood gases and electrolytes inside and outside the erythrocytes were investigated in 3 groups of subjects: type I respiratory failure patients (group 1, n = 40); type II respiratory failure patients (group 2, n = 40) and controls (group 3, n = 37). The results showed that (1) anion transport function impairment of erythrocyte membrane band 3 protein and HCO3-/Cl- exchange restrain may be the reasons that aggravate CO2 retention and respiratory acidosis in cor pulmonale patients with type II respiratory failure. (2) band 3 protein anion transport function impairment in patients of cor pulmonale with type II respiratory failure is reversible. Therefore, it was necessary to supply oxygen to cor pulmonale patients with hypoxemia in time, which may contribute to the recovery of anion transport function.

Aged↗