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Biomedical subjects

H Fritzsche

Publications and source records attributed to H Fritzsche.

At least 91 records · Page 5Linked to original sources
PubMed1982

Studies on interaction of anthracycline antibiotics and deoxyribonucleic acid: geometry of intercalation of iremycin and daunomycin.

The structure of iremycin [10-(alpha-L-rhodosaminyl)-gamma-rhodomycinone] hydrochloride has been confirmed by 1H and 13C nuclear magnetic resonance (NMR) spectroscopy. We studied the interaction of iremycin and the related compound daunomycin with DNA by transient electric dichroism and by sedimentation analysis of supercoiled closed duplex DNA. The apparent length increase of sonicated calf thymus DNA (150 +/- 20 base pairs) in 2.5 mM sodium cacodylate buffer (pH 7) at 12 degrees C was determined to be 0.40 +/- 0.02 nm/bound drug). The Cu(II) complex of iremycin with a metal/drug ratio of 0.7 induces a length increase of DNA of 0.44 +/- 0.02 nm/added drug. The alignment of the iremycin chromophore with respect to the DNA helix axis was determined from the electric dichroism of the complex. The tilt (long axis) and twist (short axis) of the chromophore are both 28 +/- 4 degrees, whereas for daunomycin the long axis is perpendicular to the helix axis and the short axis is twisted by about 25 degrees. Intercalation of iremycin between DNA base pairs is supported by unwinding of the supercoiled closed duplex form of pBR 322 plasmid DNA from Escherichia coli. In 2.5 mM sodium cacodylate buffer at pH 7 and at 25 degrees C, the unwinding induced by iremycin is 15.0 +/- 1.5 degrees/bound drug. Under identical conditions daunomycin shows on unwinding angle of 15.4 +/- 1.5 degrees. The superhelical density of pBR 322 DNA (sigma 0) was determined to be -0.087 +/- 0.002 at standard conditions (0.2 M NaCl, 37 degrees C).

Anthracyclines↗
PubMed1981

Structure and architecture of the bacterial virus fd. An infrared linear dichroism study.

Oriented gels of intact bacterial virus fd have been invetigated by infrared linear dichroism. Infrared absorption band maxima and dichroism indicate an alpha-helix content of the major coat protein of 95-100%. The alpha-helical rods of the coat protein are aligned parallel to the long axis of the virion with an inclination roughly estimated to approximately 37 degree. The presence of DNA infrared bands at 968, 885, 830 and 799 cm-1, the absence of a band at 860 cm-1 and the perpendicular polarization of the symmetric PO-2 stretching vibration at 1085 cm-1 are all indicative of a B-type backbone conformation in the single-stranded DNA. We find no evidence for specific interaction between aromatic side groups (phenylalanine, tyrosine) and the DNA bases. Our results independently confirm most features of the model of Marvin and co-workers [2,15 ] based on low-resolution X-ray diffraction studies. However, our findings contradict their suggestion of an A-type DNA in the bacterial virus fd. Two results are consistent with rigid and stable order in the virus. First, over a 4-day period, 65% of the peptide hydrogens remain unexchanged with deuterium. Second, changes in the relative humidity of the sample do not result in any shifts in the DNA spectrum that are characteristic of free DNA.

Coliphages↗
PubMed1980

A new conformation-specific infrared band of A-DNA in films.

A band at 1185 cm-1 occurs in the infrared spectra of nucleic acids in their A-type conformation which has been reproduced in the literature, too. The absorbance of this band is proportional to the fraction of the A form of DNA samples containing a mixture of different forms. The 1185 cm-1 band has been assigned tentatively to a vibration of the sugar-phosphate backbone with a fairly high contribution from the sugar moiety. Drastic dehydration of the DNA films is accompanied by a continuous intensity decrease of the 1185 cm-1 band indicating a collapse of the A form.

Animals↗
PubMed1980

On the interaction of caffeine with nucleic acids. III. 1H NMR studies of caffeine--5'-adenosine monophosphate and caffeine-poly(riboadenylate) interactions.

1) The self-association of both caffeine (Cf) and 5'-adenosine monophosphate (AMP) in aqueous solution has been reinvestigated by 1H NMR. The self-association process is characterized by an isodesmic model. The apparent self-association constants of the vertical stacking process are KCf = (10.6 +/- 1.0) M-1 and KAMP = (1.67 +/- 0.17) M-1. The arrangement of the monomeric units in the stacked aggregates is discussed in terms of isoshielding curves theoretically calculated by Giessner-Prettre and Pullman. Models are proposed which are consistent with these and further previous NMR data. 2) The interaction of Cf and AMP has been studied by 1H NMR. The apparent association constant of the complex Cf-AMP is KC-A = (7.3 +/- 1.2) M-1. Two models of the mutual arrangement of AMP and Cf in the complex are proposed on the basis of the calculated isoshielding curves considering both ring current and local atomic diamagnetic anisotropy effects. 3) The interaction of Cf and poly(riboadenylate), (rA)n, is indicated by a downfield shift of the H-8 line but an upfield shifts of the H-2 line in the 1H NMR spectra of (rA)n. The concentration dependence of the 1H NMR shifts of both Cf and (rA)n can be explained by the existence of two binding mechanisms. We suggest (i) partial insertion of Cf between adjacent base residues of ordered single-stranded regions of (rA)n and (ii) outside binding of Cf in form of monomeric Cf as well as of self-associated aggregates. The complex geometry of insertion proposed on the basis of the calculated isoshielding curves is characterized by a stronger overlapping of the Cf ring and the H-2 proton of (rA)n as compared to the H-8 proton.

Adenosine Monophosphate↗
PubMed1980

On the interaction of caffeine with nucleic acids. IV. Studies of the caffeine-DNA interaction by infrared and ultraviolet linear dichroism, proton and deuteron nuclear magnetic resonance.

The DNA-caffeine interaction at high concentration of caffeine (Cf) leads to an arrangement of Cf molecules outside of the DNA double helix with an orientation parallel to the bases both in the A and B form as demonstrated by infrared linear dichroism. Addition of DNA broadens the 1H NMR lines of Cf in aqueous solution indicating a specific binding. Intercalation is not the predominant mechanism, the deuterium relaxation time T1 = (38 +/- 7) ms and the estimated reorientation correlation time tau cb = 0.17 ns of caffeine-8[2H] in the Cf-DNA complex suggest an outside stacking of the ligand. According to the results a model on the DNA-Cf complex at high Cf concentration (binding process II) is suggested including the caffeine-induced reorientation of the hydration shell of DNA.

Caffeine↗
PubMed1978

[Serum concentrations of thyroid hormones in severe non-thyroidal illnesses (author's transl)].

Pathologically low serum total triiodothyronine (T3) concentrations are a characteristic finding in patients with severe non-thyroidal illnesses. No adequate explanation has yet been offered for this phenomenon. We have, therefore, investigated the serum concentrations of total thyroxine (T4), total T3 and total 3,3',5'-triiodothyronine (reverse T3)--the metabolically-inactive metabolite of thyroxine--and of TSH in 13 patients with acute myocardial infarction, in 12 patients with compensated liver cirrhosis, in 9 patients with decompensated liver cirrhosis and in 15 patients with chronic renal failure on chronic intermittent haemodialysis by radioimmunoassay. The values obtained were compared to corresponding values of a normal control group (n - 23). According to our results the decrease in serum T3 combined with normal T4 concentrations in severe non-thyroidal illnesses seems to be a consequence of an alteration in thyroxine degradation. Two different possibilities of alteration can be considered: 1. inhibition of the overall deiodinationof T4, leading to low total T3 serum concentrations with concomitant normal to low reverse T3 serum concentrations (chronic uraemia), 2. a shift in the monodeiodination of T4 towards enhanced reverse T3 production, leading also to low total T3 concentrations, but with a concomitant increase in reverse T3 serum concentrations (myocardial infarction, liver cirrhosis). The results obtained in our patients with liver cirrhosis show, moreover, that this alteration of T4 metabolism depends on the severity of the illness.

Humans↗
PubMed1977

[Determination of pregnancy duration following terminated hormonal contraception].

The duration of pregnancy as assessed by the rule of Naegele was significant different between patients who became pregnant following termination of oral contraception and patients, who had not taken oral contraceptives. The intervall between stopping the pill and pregnancy was two month. We found a relatively high pregnancy rate in the first three month. The clinical significance is discussed.

Contraception↗
PubMed1977

[Screening for hypothyroidism in the newborn with a total T 4-RIA method (author's transl)].

A screening method for detection of congenital hypothyroidism is presented in detail in cooperation with the "Austrian Program for Inborn Errors of Metabolism". Screening is performed by measuring the total T4-content of 1/8 inch filter paper dots filled with dried blood of newborns. The strategy for recall of newborns with borderline or pathological T4-values used, results in a definite diagnosis on day 55 of life. The advantages of additional TSH determination in the filter paper dots are discussed. So far (Sept. 1976) 8645 newborns have been investigated, covering the regions of Vienna and Carinthia (Austria). Preliminary studies reveal a slight dependency of the measured T4-values on the day of sampling. Two congenitally hypothyroid children have been diagnosed so far, corresponding fairly well with the reported frequency in the literature (1 : 6000).

Humans↗