A case of fetal decapitation.
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Abnormalities, Multiple↗
Biomedical subjects
D Genest
Publications and source records attributed to D Genest.
Rigid-body motions of sub-units in DNA: a correlation analysis of a 200 ps molecular dynamics simulation.
A 200 ps molecular dynamics simulation of the B-form double stranded self-complementary octanucleotide d(CTGATCAG) is analyzed in terms of correlated motions using the canonical analysis approach. Each nucleotide is decomposed in three sub-units corresponding to the base, the sugar ring and the backbone respectively. The correlation between the full dynamics of two sub-units was found to decrease as their mutual distance increases. The interpretation of the full dynamics of sub-units as the superimposition of rigid-body motions (translation and orientation) and deformation shows that the main source of correlation is rigid-body motions. Correlation between sub-units deformation is weak and practically vanishes for sub-units belonging to non-adjacent nucleotides. It is also shown that the correlation is much more important for sub-units of the same strand than of opposite strands. We conclude that the internal dynamics of the octanucleotide may be well described by rigid-body motions, the sub-units deformation having only local influence whereas sub-units translation and rotation have repercussion to long distances. The results presented in this study suggest how the number of degrees of freedom may be reduced for simulating long-time dynamics of oligonucleotides.
Computer Simulation↗
Markedly increased tissue concentrations of 7-dehydrocholesterol combined with low levels of cholesterol are characteristic of the Smith-Lemli-Opitz syndrome.
The Smith-Lemli-Opitz syndrome is an autosomal recessive birth defect (frequency 1:20,000-1:40,000) that results in profound mental retardation, physical deformities, and failure to thrive. It is characterized biochemically by low plasma cholesterol and greatly elevated levels of two dehydrocholesterols, one of which is the cholesterol precursor 7-dehydrocholesterol. To determine whether the block in cholesterol biosynthesis affects tissue sterols, we assayed several organs from two affected individuals, a female who died at 27 hours and a 20-week male fetus. Cholesterol concentrations in abdominal wall, adrenal gland, and kidney from two or three unaffected fetuses, who served as controls, averaged 2.0, 1.5, and 1.4 mg/g wet weight, compared to 0.08, 0.44, and 0.14, respectively, for the homozygous fetus. Cerebral cortex cholesterol concentrations were 2.2 mg/g for two 20-22-week fetal controls but only 0.21 and 0.09 mg/g, respectively, for the homozygous child and fetus. Similarly, tissue cholesterol levels were abnormally low in the homozygous child being less than 1 mg/g in liver, adipose, thymus, muscle, and adrenal and 6.2 mg/dl in plasma. Dehydrocholesterols could not be detected by conventional means in any controls but were elevated enough in tissues from affected individuals to make total sterol concentrations nearly normal. These results suggest that a defect in 3 beta-hydroxysterol delta 7-reductase leads to both a profound lack of cholesterol and its replacement by dehydrocholesterols. Such a combination may be lethal in the most severely affected individuals.
Abnormalities, Multiple↗
Canonical analysis of correlated atomic motions in DNA from molecular dynamics simulation.
We report a method for analyzing atomic correlated motions in biopolymers from trajectories obtained by molecular dynamics simulation. A correlation coefficient based on the canonical analysis of data is defined which is independent on the relative orientation of atomic displacement. To illustrate the method we studied correlation between positional fluctuations of protons in the double-stranded self complementary oligonucleotide d(CTGAT-CAG), deduced from a 200 ps molecular dynamics simulation in the presence of explicit water molecules and counterions. It is found that on this time scale the motions of protons belonging to different residues are poorly coupled while the motion of a base proton is correlated to the motion of the sugar ring protons of the same nucleotide. Such a method may be generalized to study correlated motions of two distinct domains of a macro-molecule.
Computer Simulation↗
Influence of a mutation in the transmembrane domain of the p185c-erbB2 oncogene-encoded protein studied by molecular dynamics simulations.
The c-erbB2 proto-oncogene encodes for a protein of 185kDa (p185) which becomes transforming upon the Val-->Glu transmembrane amino acid substitution. The transforming ability seems to be due to a substitution-resulting constitutive activation of the tyrosine kinase cytosolic domain of the protein. These observations prompted us to evaluate the structural and dynamical behavior of the transmembrane region of the wild and transforming p185 protein in order to understand the role of this region in the transduction mechanism. 160 ps molecular dynamics simulations in vacuo have been performed on two peptides corresponding to the sequence [651-679] of p185c-erbB2 protein and its transforming mutant Val659-->Glu659. These two sequences include the transmembrane domain and are initially postulated to be in an alpha-helix conformation. Noticeable differences in the flexibility of the two peptides are shown. The nontransforming sequence seems rather flexible and several conformational changes are detected at the junction of the mutation point [658-659] and at position Val665-Val666 during the 160 ps simulations. On the contrary, no transitions were observed for the mutated sequence which adopts a stable alpha-helix conformation. This difference in flexibility could be hypothesized as a factor involved in the regulation of the tyrosine kinase activity of p185c-erbB2.
Amino Acid Sequence↗
Molecular dynamics study of the base pair opening process in the self-complementary octanucleotide d(CTGATCAG).
We report an analysis of a 200 ps Molecular Dynamics simulation of the double stranded oligonucleotide d(CTGATCAG) in the presence of 1534 water molecules and 14 Na+ ions. We focus on the opening process of Thymine 5, by analyzing in detail the glycosidic bond rotational motion about the helix axis. The present analysis is mainly based on autocorrelation functions and on mean square displacements. We show that the opening of the base has a Brownian character and we find a rotational diffusion coefficient of 4.7 rad2s-1. Furthermore we estimate the DNA torsional constant to be about 0.5 10(-18) J.rad-2 and the RMS of the angular displacement to be 8.3 degrees. All these values are in fair agreement with those determined experimentally by fluorescence polarization of DNA-Ethidium bromide complexes. This shows that the rotational motions of the bases detected in the range 10(-9)-10(-7) s. by fluorescence techniques are the same as those analyzed in the present study (10(-12)-2 10(-10) s).
Base Composition↗
Cardiac histologic pathology characteristic of trisomies 13 and 21.
To identify fetal histologic features characteristic of specific chromosomal anomalies, we reviewed histologic slides of 415 cases, including therapeutic and spontaneous abortuses, stillbirths, and perinatal deaths. These included 126 cases (30%) with karyotypically confirmed trisomy 21 and 23 cases (5.5%) with trisomy 13. Two histologic abnormalities of the fetal heart were identified that correlated with specific karyotypic abnormalities: (1) a discrete central papillary muscle calcification was present in 14 of 85 (16%) cases with trisomy 21, in seven of 18 (39%) cases with trisomy 13, and in six of 255 (2%) controls (P less than .001); and (2) a focal ventricular epicardial lymphocytic infiltrate was present in 22 of 93 (24%) cases with trisomy 21 versus nine of 284 (3%) controls (P less than .001). When both histologic abnormalities coexisted, trisomy 21 was present in five of six cases (83%). Neither histologic finding was significantly associated with fetal or maternal infection or congenital heart defects. In a restricted prospective study of the hearts of fetuses with trisomy 21, papillary muscle calcification was demonstrated by specimen radiographs in four of six (67%) cases; one case was studied by specimen ultrasonogram, which identified a papillary muscle echodensity. We conclude that (1) a focal ventricular epicardial lymphocytic infiltrate is characteristic of trisomy 21, (2) papillary muscle microcalcifications are characteristic of trisomies 13 and 21, and (3) further studies are needed to determine whether papillary muscle calcification might be useful in antenatal ultrasonographic screening for chromosomal anomalies.
Calcification, Physiologic↗
Ovarian granulosa-stromal cell tumors are characterized by trisomy 12.
Eleven ovarian granulosa-stromal cell tumors including 1 thecoma, 2 fibromas, 6 fibrothecomas, and 2 granulosa cell tumors, were karyotyped after direct harvest and/or short-term tissue culture. Bilateral fibrothecomas from one patient appeared to lack cytogenetic aberrations: the remaining nine tumors were characterized by trisomy for chromosome 12. Cytogenetic aberrations in the two granulosa cell tumors were much less complex than those described previously in undifferentiated carcinomas; accordingly cytogenetic analyses might be useful in distinguishing these categories. The consistent occurrence of trisomy 12 in different varieties of granulosa-stromal cell tumors suggests a common mechanism of oncogenesis within this diverse group of neoplasms. That mechanism probably involves promotion of low-grade, orderly cell proliferation.
Chromosomes, Human, Pair 12↗
A 2D NMR study of the internal flexibility of the antifungal peptide stendomycin.
A 2-D 1H NMR study (NOESY, COSY, HOHAHA and ROESY experiments) of the antifungal peptide stendomycin is presented. The variation of the NOESY cross peak intensities is measured as a function of temperature in order to discriminate between constant and fluctuating interproton distances. It is shown that among 71 NOESY cross peaks, only 12 correspond to well defined interproton distances and their correlation time is determined. The other cross peaks cannot be translated accurately in terms of distances owing to internal molecular motions. (1H)-13C nOe measurements confirm the internal mobility of the molecule. Finally a flexibility map of stendomycin can be established.
Amino Acid Sequence↗
A Monte Carlo simulation study of the influence of internal motions on the molecular conformation deduced from two-dimensional NMR experiments.
Monte Carlo methods have been used to simulate internal motions of aromatic protons of an oligonucleotide at the nanosecond time scale. Each proton is allowed to fluctuate about its equilibrium position. The longitudinal cross-relaxation rates of such a system of spins have been determined by computing the appropriate correlation functions. Then the interproton distances have been deduced according to the procedure generally used in two-dimensional nmr techniques (nuclear Overhauser effect spectroscopy--NOESY) and compared to the true values. The influence of the amplitude A and of the internal rotational diffusion constant Dint characterizing the dynamics of the system has been checked for in-phase and for uncorrelated motions. It is shown that for the investigated models the distances deduced from NOESY experiments may be under- or overestimated, depending strongly on the values of A and Dint. Furthermore, the cross-relaxation rate of a couple of protons is very sensitive to the correlation level of the motions of both protons.
Cytosine↗
Medullary carcinoma of the breast: mammographic and US appearance.
Medullary carcinoma of the breast is an uncommon tumor, which may mimic a benign mass at both mammography and ultrasonography (US). A total of 24 medullary carcinomas visible at mammography appeared as round or oval, noncalcified masses with varying degrees of marginal lobulation. In six of the 24 patients, US demonstrated well-defined masses with an inhomogeneous, hypoechoic texture. There was no attenuation of sound, and all lesions showed enhanced through transmission.
Adult↗
Micellization and interactions with phospholipid vesicles of the lipopeptide iturin A, as monitored by time-resolved fluorescence of a D-tyrosyl residue.
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Anti-Bacterial Agents↗
Two-dimensional 1H NMR study of d(br5C-G)3 in the Z-form. Self association and flexibility of the left-handed double helix.
The Z conformation of the auto complementary hexanucleoside pentaphosphate d(br5C-G)3 in 1 M NaClO4 solution has been investigated by using 2D NMR techniques. NOESY experiments performed at different temperatures show that the oligonucleotide exhibits end-to-end associations at room temperature. The conformation of the hexanucleotide molecules is very similar to that found in the crystal which was described by Chevrier et al. (J. Mol. Biol., 1986, 188, 707-719) as a Z-I form. When the temperature is increased the aggregates are dissociated and a conformational change is observed which is interpreted as a Z-I in equilibrium Z-II transition.
DNA↗
Fluorescence decay of ethidium bromide in the presence of the Z-conformation of poly(dG-dC) and of poly(dG-dC) modified by chlorodiethylenetriamine platinum(II) chloride.
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Cisplatin↗
Thermal stability of the Z conformation of the hexanucleoside pentaphosphate d(br5CGbr5CGbr5CG): evidence for a conformational transition before melting.
The thermal stability of the hexanucleoside pentaphosphate d(br5CGbr5CGbr5CG) has been studied at two nucleotide concentrations, in the presence of 1 M NaClO4. At low nucleotide concentration (7 X 10(-5) M), circular dichroism experiments show a conformational transition from the Z conformation to another conformation, named X, which is not the B conformation, as the temperature is increased from 0 to 35 degrees C. Between 40 and 65 degrees C, another transition is observed which corresponds to the melting of the X conformation. At higher nucleotide concentration (2 X 10(-3) M), circular dichroism and 31P nuclear magnetic resonance experiments show that at low temperature (br5dC-dG)3 adopts the Z conformation. There are associations between the oligonucleotides which progressively disappear as the temperature increases. In the range 35-60 degrees C a transition from the Z conformation to another conformation is observed. This new conformation is the X conformation detected at low nucleotide concentration.
Circular Dichroism↗
The preferential location of the human Y chromosome in somatic metaphase. I. Influence of Y polymorphism.
The location of the Y chromosome in metaphase figures was studied, with respect to its polymorphism, on 700 micrographs from blood lymphocyte cultures from 70 normal male members of seven Canadian family lines whose polymorphic Y chromosomes were inherited in a patrilinear fashion from seventeenth-century French ancestors. Three of these family lines were carriers of a long Y chromosome, two a small one, one had an average length Y and a seventh one had a satellited Y marker. The Y chromosome was peripheral in 75 to 90 per cent of the metaphase plates from each individual investigated. The long Y markers were more peripheral than the small ones while the average length Y chromosome had an intermediate position, whereas the satellited Y chromosome was located within the small group. The difference between the location of the long and the small Y chromosomes was highly significant. It is hypothesised that a heteromorphic Y might affect the nonrandom orientation of metaphasic chromosomes and favour meiotic nondisjunction and aneuploidy.
Cells, Cultured↗
[Behavior of pressure and flow parameters of pulmonary circulation in bronchologic studies in general anesthesia using 2 injectable anesthetics].
Flow- and pressure-parameters of the pulmonary circulation were measured in the course of bronchologic investigations under general anaesthesia using as narcotics in group I (n = 14) Hexobarbital, in group II (n = 10) Propanidid (Sombrevin). The increase of mean pulmonary artery and mean PCW-pressure in group II is significantly higher than in group I. This seems to be caused by a more reduced myocardial function due to Sombrevin. Heart rate and pulmonary vascular resistance increase in both groups uniformly. The pO2 is markedly reduced up to 4 hours after the investigation accompanied by an increase of pCO2.
Adult↗
Investigation of DNA dynamics and drug-DNA interaction by steady state fluorescence anisotropy.
We have used steady-state fluorescence polarization anisotropy (FPA) of ethidium probe molecules bound to DNA to investigate DNA-DNA interactions and the effect of high densities of intercalating drugs on the internal motions of DNA responsible for depolarization of the ethidium fluorescence. To calibrate the method, we examined the effect of DNA length on (FPA) using DNA varying in size from 10-150 base pair. The association of approximately 30 base pair DNA at high concentrations was then detected by its effect on (FPA). With sample concentrations approaching those commonly used in various physical experiments (NMR, Raman) significant DNA-DNA interactions are observed. With high molecular weight DNA (greater than 500 base pair), the limiting value of the (FPA) (0.23) is due to internal motions of the DNA (and bound chromophores). The (FPA) of ethidium probe molecules (1 drug/200 base pair) is unaffected by the addition of high levels (1 drug/2 base pair) proflavine. This indicates that either the elastic properties of DNA are unaffected by high densities of intercalated drug or that the depolarization of the ethidium fluorescence is due to highly localized motions of the base pairs that are unperturbed by binding of drugs at neighboring sites.
Acridines↗