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Biomedical subjects

R Savoie

Publications and source records attributed to R Savoie.

12 recordsLinked to original sources

Gestational trophoblastic disease.

OBJECTIVE: To provide standards for the diagnosis and treatment of patients with hydatidiform mole and gestational trophoblastic tumours (GTT). OPTIONS: Prognostic factors useful for treatment decisions in GTT are defined with patients classified as low-, medium-, and high-risk groups. OUTCOMES: Improved mortality and morbidity. EVIDENCE: Evidence was gathered using Medline for relevant studies and articles from 1980 to 2001 with specific reference to diagnosis, treatment options, and outcomes. The quality of evidence of Recommendations has been described using the Evaluation of Evidence criteria outlined in the Report of the Canadian Task Force on the Periodic Health Exam. RECOMMENDATIONS: 1. Suction curettage is the preferred method of evacuation of the hydatidiform mole (III-C). Post-operative surveillance with hCG assays is essential (II-3B). 2. Low-risk patients with both non-metastatic and metastatic disease should be treated with single-agent chemotherapy, either methotrexate or dactinomycin (II-3B). 3. Medium-risk patients should usually be treated with multi-agent chemotherapy, either MAC or EMA (III-C); single-agent chemotherapy may also be used (III-C). 4. High-risk patients should be treated with multi-agent chemotherapy EMA/CO, with selective use of surgery and radiotherapy (II-3B). Salvage chemotherapy with EP/EMA and surgery should be employed in resistant disease (III-C). 5. Placental site trophoblastic tumour that is non-metastatic should be treated with hysterectomy (III-C). Metastatic disease should be treated with chemotherapy, most commonly EMA/CO (III-C).6. Women should be advised to avoid pregnancy until hCG levels have been normal for six months following evacuation of a molar pregnancy and for one year following chemotherapy for gestational trophoblastic tumour. The combined oral contraceptive pill is safe for use by women with GTT (III-C). VALIDATION: These guidelines have been reviewed and approved by the Policy and Practice Guidelines Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC), the Gynaecologic Oncologists of Canada (GOC), the Society of Canadian Colposcopists (SCC), and by Executive and Council of the SOGC. SPONSOR: The Society of Obstetricians and Gynaecologists of Canada.

Antineoplastic Agents↗

A vibrational spectroscopic study of the metastable form of associated polyinosinic acid.

We have studied by Raman and ir spectroscopy the metastable complex formed by the self-association of polyinosinic acid in aqueous solution. The complex is easily prepared by quickly cooling to ca. 0 degrees C a warm solution of the polyribonucleotide to which a small amount of rubidium salt has been added. Upon heating, this metastable form melts cooperatively near 13 degrees C, well below the dissociation temperature of a stable four-stranded complex, which occurs at 47 degrees C in the same conditions. The presence of several components in the stretching-mode region of the carbonyl groups in the vibrational spectra of the metastable complex suggests that it also has a parallel four-stranded structure. The difference in structure between the two forms is believed to be caused by the presence of fewer metal ions in the central channel of the metastable complex, in agreement with conclusions reached in previous investigations. The Raman spectra further show that the ribose units in the metastable form have a C3'-endo conformation, in contrast with the stable form, for which we have previously suggested a mixed C2'-endo/C3'-endo conformation.

Drug Stability↗

A vibrational spectroscopic study of the self-association of polyinosinic acid and polyguanylic acid in aqueous solution.

We have studied by Raman and ir spectroscopy the structure of self-associated polyinosinic acid and polyguanylic acid in aqueous solution. The results are consistent with the formation of a four-stranded complex, which melts cooperatively near 60 degrees C in the case of poly(I) in the presence of K+ ions. The conformation of the ribose in both systems is mixed C2'-endo/C3'-endo, giving a structure that is intermediate between the extremes proposed previously from x-ray diffraction studies. Characteristic Raman bands for the C2'-endo ribose conformation in polyribonucleotides are identified. The four-stranded structure of poly(I) appears to be very flexible, with approximately 15% of the tetrameric segments being disrupted and approximately 30% of the ribose units adopting a disordered conformation prior to melting. This disordering process increases to approximately 75% above the melting transition, with the remaining approximately 25% of the ribose units keeping an ordered C2'-endo or C3'-endo conformation.

Nucleic Acid Conformation↗

Raman spectroscopic study of the effects of Ca2+, Mg2+, Zn2+, and Cd2+ ions on calf thymus DNA: binding sites and conformational changes.

The interaction of Mg2+, Ca2+, Zn2+, and Cd2+ with calf thymus DNA has been investigated by Raman spectroscopy. These spectra reveal that all of these ions, and particularly Zn2+, bind to phosphate groups of DNA, causing a slight structural change in the polynucleotide at very small metal: DNA (P) concentration ratio (ca. 1:30). This results in increased base-stacking interactions, with negligible change of the B conformation of DNA. Contrary to Zn2+ and Cd2+, which interact extensively with the nucleic bases (particularly at the N7 position of guanine), the alkaline-earth metal ions are bound almost exclusively to the phosphate groups. The affinity of both the Zn2+ and Cd2+ ions for G.C base pairs is comparable, but the Cd2+ ions interact more extensively with A.T pairs than Zn2+ ions. Interstrand cross-linking through the N3 atom of cytosine is suggested in the presence of Zn2+, but not Cd2+.

Animals↗

A laser Raman spectroscopic study of the interaction of the methylmercury cation with AMP, ADP and ATP.

The interaction of the CH3Hg+ cation with adenosine 5'-monophosphate, adenosine 5'-diphosphate, and adenosine 5'-triphosphate has been studied in aqueous solution at neutral pH by laser Raman spectroscopy. Metal binding is shown to occur preferentially at the N-1 ring position of adenine, with some indication of coordination to the N-7 site and substitution of a proton on the exocyclic NH2 group of the nucleic base. Binding of the cation to phosphate groups also occurs extensively, with both the -PO2-3 and -PO-2 groups. The equilibrium constants for the binding to the phosphate groups and for N-1 coordination are approx. 70 and 600 M-1, respectively.

Adenosine Diphosphate↗

A laser Raman spectroscopic study of the interaction of calf-thymus DNA with Cu(II) and Pb(II) ions: metal ion binding and DNA conformational changes.

The interaction of calf-thymus DNA with Cu(II) and Pb(II) ions has been investigated in H2O and D2O solutions at physiological pH, using laser Raman spectroscopy. The results confirm the destabilizing effect of Cu2+ ions, which are shown to bind strongly to the guanine and cytidine bases, perturbing the A-T base pairs and disrupting the double-helical structure of DNA, whose conformation is markedly altered by these interactions. Earlier claims that Pb2+ ions destabilize DNA are not supported by the present study. These ions are found to interact only weakly with the nucleic bases, binding to the N7 position of the guanine bases and also interacting with the A-T pairs. Both types of ions are found to interact with the charged phosphate groups of DNA, although these sites are preferred over the nucleic bases by Pb2+ ions.

Copper↗

Effect of the action potential on the Raman spectrum of the pike olfactory nerve.

Raman bands due to the C-H stretching vibrations of the phospholipid acyl chains, as well as those due to resonance enhanced vibrations of carotenoid pigments, were used to probe for conformational changes during the passage of the action potential through fibers of the pike unmyelinated olfactory nerve. Our results show that if there are any spectral changes during nerve excitation, these are less than 0.5% for both the phospholipid and the carotenoid bands.

Action Potentials↗

Laser Raman spectra of calf thymus chromatin and its constituents.

Extensive Raman measurements have been made on calf thymus chromatin, core chromatin, the (H3,H4)/DNA complex, and isolated DNA. The results indicate that the alpha-helical content of the nucleosomal histones gradually increases as they form the heterocomplexes that lead to the formation of the octameric nucleosome core. The secondary structure of the latter is not modified as it binds to DNA. The spectra indicate that the DNA essentially retains its B conformation in nucleosomes, although slight changes probably occur in the ribose-phosphate backbone. No specific interactions between the nucleosomal histones and DNA can be established from the spectra, but histone H1 possibly interacts selectively with the thymine bases.

Animals↗

Conformations of calf thymus and rye histones H3 and H4 in aqueous solution by laser Raman spectroscopy.

The Raman spectra of aqueous solutions of histones H3 and H4 from calf thymus and from rye reflect the high degree of conservation from species to species of the primary and secondary structures of these proteins. The amount of beta-sheet structure is estimated at 40 +/- 5% in H4 and at 33 +/- 5% in H3 from the intensities of the amide I and amide III bands at 1663 and 1241 cm-1, respectively, in the spectra. These values are independent of the salt concentration of the solutions, mostly likely because of the high histone concentration (approximately 3 mM) required to obtain the spectra, which results in some aggregation of the proteins. The intensity ratio of the tyrosine doublet at 852 and 826 cm-1 indicates that the four tyrosine residues in H4 are relatively exposed to the solvent or weakly bound to positively charged groups of basic amino acids, whereas in H3 at least one tyrosine is buried inside the protein and tightly bound to a carboxylate group. The results also show that the secondary structure of H3 is slightly influenced by the state of oxidation of the two cysteine residues it contains.

Animals↗

Laser Raman investigation of intact single muscle fibers. On the state of water in muscle tissue.

Laser Raman spectroscopy has been used to investigate the state of water in intact single muscle fibers of the giant barnacle (Balanus nubilus). The spectra in the region of the O-H (or O-2H) stretching modes of water in unfrozen fibers show that there is no appreciable difference between the shape and relative intensity of the Raman bands due to the water molecules located inside a muscle fiber and those of the corresponding bands in the spectrum of pure water. The presence of significant amounts of "structured" intracellular water, greater than approx. 5% of the total water content, in these fibers is thus excluded. The Raman spectra of frozen fibers have also been recorded in order to evaluate the amount of intracellular water which remains unfrozen at temperatures below the normal freezing point of water. We have been able to reproduce these spectra by assuming that the spectrum of a frozen fiber is the sum of the individual spectra of water and ice. To calculate the amount of unfrozen water from these curve fittings, it was also necessary to determine the intensities of the water and ice Raman bands relative to one another. We have found the I(ice)/I(water) ratio is 1.07 +/- 0.01 for H2O and 1.05 +/- 0.03 for 2H2O With these figures, we have calculated that for a fiber with a normal water content of 80%, 20% of the water molecules remain in the supercooled state of -5 degrees C, which corresponds to 1 g of water per g of fiber dry weight. This amount of bound water was also found to be independent of the water content of the fibers.

Animals↗