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Biomedical subjects

B Hartmann

Publications and source records attributed to B Hartmann.

At least 181 records · Page 10Linked to original sources

Guanine and 7-methylguanine amino proton exchange rates as a function of buffer pK: implications for the exchange mechanism.

Using the stopped-flow kinetic method we have measured the deuteration rate of the amino protons in 2'deoxyguanosine 5'monophosphate and 7-methylguanosine 5'monophosphate. For both compounds the exchange rates are accelerated with increasing concentration of a large number of buffers with widely differing pKs. The results obtained, in conjunction with a theoretical model study, give rise to serious doubts concerning the normally accepted mechanism of amino proton exchange involving a pre-protonation at N7.

Buffers↗

Poly(dA-dT).poly(dA-dT) two-pathway proton exchange mechanism. Effect of general and specific base catalysis on deuteration rates.

The deuteration rates of the poly(dA-dT).poly(dA-dT) amino and imino protons have been measured with stopped-flow spectrophotometry as a function of general and specific base catalyst concentration. Two proton exchange classes are found with time constants differing by a factor of 10 (4 and 0.4 s-1). The slower class represents the exchange of the adenine amino protons whereas the proton of the faster class has been assigned to the thymine imino proton. The exchange rates of these two classes of protons are independent of general and specific base catalyst concentration. This very characteristic behavior demonstrates that in our experimental conditions the exchange rates of the imino and amino protons in poly(dA-dT).poly(dA-dT) are limited by two different conformational fluctuations. We present a three-state exchange mechanism accounting for our experimental results.

Deuterium↗

A study of the thermal stability of the Z form of (m5dC-dG)3 by resonance Raman spectroscopy.

The thermal stability of the hexanucleoside pentaphosphate m5dCpdGpm5dCpdGpm5 dCpdG has been studied by resonance Raman spectroscopy with 257 nm excitation wavelength. At low temperature and in 3M NaClO4, the Raman spectrum resembles that of poly(dG-dC).poly(dG-dC) in the Z conformation. As the temperature is increased, the position and the intensity of several bands (1312 cm-1, 1482 cm-1, 1584 cm-1 and 1632 cm-1) are modified. The variation of intensity versus temperature is biphasic. Analysis of the results suggests that the increase of temperature induces first a transition from the Z form to an intermediate stable form which then melts. These results and those previously obtained by circular dichroism and 31P nuclear magnetic resonance suggest that the intermediate form belongs to the left family but with changes in the stacking of the bases and the geometry of the phosphate groups as compared to the canonical Z form.

Circular Dichroism↗

Solvation of the left-handed hexamer d(5BrC-G-5BrC-G-5 BrC-G) in crystals grown at two temperatures.

Crystals of the hexadeoxyoligomer d(5BrC-G-5BrC-G-5BrC-G) were grown at different temperatures (5 degrees C, 18 degrees C and 37 degrees C) in the absence of divalent cations. The crystals grown at 5 degrees C did not diffract X-rays, while those grown at 18 degrees C and 37 degrees C did. The oligomer adopts the left-handed ZI conformation in both crystals. The main difference resides in a more extensive hydration shell in the crystal grown at high temperature than in the crystal grown at low temperature. The high-temperature crystal displays a spine of hydration running deep in the minor groove and linking exocyclic O-2 atoms of the pyrimidine rings. In both crystalline forms, a hydrated sodium ion bound to the N-7 of a guanine ring was found. Strings of water molecules bridging phosphate anionic oxygen atoms are found along the backbone. The absolute values of the propeller-twist are also different in both structures although the values of the twist are very similar. The results point to the importance of the crystallization conditions when analysing fine structural details like solvation properties of oligomers.

Crystallization↗

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↗

Identification of alcohol abuse and alcoholism with biological parameters.

The prevalence and incidence of heavy alcohol consumption are major problems which have been increasing in many countries in recent years. It is crucial for physicians to consistently identify early drinking problems as well as the various end disease states in order to minimize suffering and maximize recovery. This paper reviews the evolutionary development of clinical tools for detection of alcohol abuse. The focus is primarily on clinical/biochemical indicators of alcohol abuse, emphasizing but not limited to changes in hematological characteristics, liver enzyme activity, lipids, immune function factors, hormones, neurological factors, and some physically based tests. Use of test combinations and sophisticated statistical analysis of pattern changes in test batteries evidence increased diagnostic efficiency.

Alcoholism↗

Plasma fatty acid pattern including diene-conjugated linoleic acid in ethanol users and patients with ethanol-related liver disease.

The level of conjugated dienes (CD) in the serum, conjugated linoleic acid isomer in the phospholipid fraction [18:2(9, 11)], and the fatty acid profile in both the serum and in the separated lipid classes were analyzed in current and previous alcohol abusers and in patients with alcoholic liver disease. None of the subjects consumed alcohol for at least 2-3 days prior to blood collection for analysis of lipids. There was no significant difference in CD or in the absolute level of 18:2(9, 11) among the groups, whereas the 18:2(9, 11)/18:2(9, 12) molar ratio was significantly elevated in patients with liver disease. Fatty acid analysis of the whole plasma extract showed that the absolute level of arachidonic acid increased from 4.8 +/- 3.5 mg/dl (n = 9) in lifelong abstainers to 13.4 +/- 4.0 (n = 8) in current ethanol abusers, and its relative level (related to the total fatty acids) from 1.73 +/- 1.34 to 4.55 +/- 1.01 in the same groups. An increased proportion of linoleic acid in the triglyceride and phospholipid fractions from current abusers and patients with liver disease was also found; the percentage of 18:2 in phospholipids increased from 5.4 +/- 5.0 (n = 8) in lifelong abstainers to 14.3 +/- 3.9 (n = 8) in current abusers and 12.7 +/- 2.2 (n = 10) in patients with liver disease. The percentage of 16:0 was significantly lower in the phospholipids of current abusers as compared to lifelong abstainers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Thermal stability of the Z-conformation of the tetranucleoside triphosphate (m5dC-dG)2.

The tetranucleoside triphosphate d(m5C-G)2 has been studied in solution by circular dichroism and 31P nuclear magnetic resonance as a function of temperature, in presence of 3 M NaClO4. It is shown that in such high ionic strength d(m5C-G)2 may adopt a Z-like conformation for temperatures lower than 5 degrees C. At these temperatures, another conformation, in slow equilibrium with the Z-like one, is also detected. Increasing the temperature leads to a transition from the Z-like conformation to intermediate forms before melting. It is demonstrated that these intermediates are not the B form.

Circular Dichroism↗