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Biomedical subjects

A Heerschap

Publications and source records attributed to A Heerschap.

At least 109 records · Page 6Linked to original sources
PubMed1993

Characterization of human prostate cancer, benign prostatic hyperplasia and normal prostate by in vitro 1H and 31P magnetic resonance spectroscopy.

In vitro 1H and 31P magnetic resonance spectra were acquired from perchloric acid extracts of human prostate tissue obtained by transurethral resection. This included tissue of patients with benign prostatic hyperplasia and prostatic adenocarcinoma; one tissue sample was obtained from a patient without any sign of BPH or malignancy. Major resonances in the magnetic resonance spectra were assigned to prostate compounds and were quantified. The citrate/lactate, citrate/total choline, phosphocholine/total creatinine, choline/total creatine, alanine/total creatine, phosphoethanolamine/total phosphate, phosphocholine/total phosphate and glycerophosphoethanolamine/total phosphate ratios were statistically different for the prostate cancer samples as compared with the BPH specimens. These observations may contribute to the understanding of in vivo magnetic resonance spectra of the prostate and indicate that magnetic resonance spectroscopy can aid in the diagnosis of prostate malignancy.

Adenocarcinoma↗
PubMed1992

Image-guided 1H NMR spectroscopical and histological characterization of a human brain tumor model in the nude rat; a new approach to monitor changes in tumor metabolism.

In this study a human glioma-derived intracerebral tumor model was analyzed histologically and examined by image-guided 1H NMR spectroscopy. It was shown that histological characteristics such as cellular subpopulation and necrosis of the primary tumor were preserved in the implants. Usually circumscript tumor growth was present with tumor cells invading the surrounding brain parenchyma. It was demonstrated that tumor growth and tumor metabolism could be monitored by image-guided 1H NMR spectroscopy in a longitudinal study. One of the initial changes noticed was the rise of the lactate signal in the tumor region followed by an increase of the choline and a decrease of N-acetyl-aspartate and phosphocreatine signals. Even before tumor invasion in brain adjacent to the central tumor area could be demonstrated by NMR imaging increased lactate and moderately increased choline signals were measured in these regions. By histopathological examination these areas were shown to be infiltrated by single tumor cells. These observations indicate that image-guided 1H NMR spectroscopy could play an important role in the study of brain tumor biology, especially in the case of changing tumor metabolism during growth.

Animals↗
PubMed1992

Magnetic resonance studies on brain dysfunction induced by organic solvents.

A 38-year-old layer of parquet flooring was referred because of memory impairment, tiredness and diffuse headaches. His work involved using several neurotoxic organic solvents. Extensive laboratory, neuropsychological, clinical neurophysiological, neuroadiological, magnetic resonance (MR) imaging and spectroscopy studies were performed. The neuropsychological and behavioural assessments showed an organic brain syndrome. MR imaging and CT scanning of the brain revealed enlarged ventricles and generalized atrophy. 31P and 1H MR spectroscopic measurements did not show any abnormalities. Owing to recent improvements regarding sensitivity and facilitated assignment, MR spectroscopy may provide in the near future significant additional information on brain metabolism in patients with brain dysfunction presumably induced by organic solvents.

Adult↗
PubMed1991

Non-invasive in vivo localized 1H spectroscopy of human astrocytoma implanted in rat brain: regional differences followed in time.

Human astrocytoma cells were cultured and inoculated into the rat brain. From the pre-clinical to the terminal state, tumour growth was monitored by in vivo MR imaging and by localized water-suppressed 1H spectroscopy (0.12-0.15 cm3 volumes) and spectroscopic imaging (0.01 cm3 voxels) employing the ACE localization technique. The MR experiments were conducted completely non-invasively, leaving the scalp intact. Brain spectra were obtained, showing distinct resonances for more than five different brain metabolites; they were not contaminated with lipid signals because of the adequate localization. Tumour progression, monitored in a selected volume of interest, was reflected in the corresponding spectra by decreasing intensities for resonances of N-acetyl aspartate and (phospho)creatine and increasing intensities for resonances of choline compounds and lactate. From spectroscopic imaging experiments metabolic heterogeneity could be deduced within the tumorous region. At particular times during tumour development spectra were obtained greatly resembling localized 1H MR spectra obtained from patients with astrocytomas by the use of similar localization methods. This emphasizes the relevance of animal model study for the evaluation of MR spectroscopic investigations in human brain tumour diagnosis and therapy evaluation.

Animals↗
PubMed1991

Early metabolic response to high energy shock waves in a human tumor kidney xenograft monitored by 31P magnetic resonance spectroscopy.

The effects of electromagnetically generated high-energy shock waves (HESW, Siemens Lithostar) on the phosphate metabolite levels of the NU-1 human kidney cancer xenograft implanted under the skin of the hind limb of nude mice were monitored by 31P magnetic resonance spectroscopy (MRS). Administration of 200 and 800 HESW (18.1 kV, P(+) = 37.5 MPa, P(-) = 5.2 MPa, tr = 30-120 nsec, tw = 340 nsec, freq. = 1.25 Hz), focused on the tumor centre, resulted in an immediate tumor decline; 2 h after exposure to the HESW, the high-energy phosphate resonances had decreased drastically. This decline in energy rich molecules was accompanied by a concomitant increase in the inorganic phosphate resonance and a decrease in pH of the tumor. During the following period, a dose-time dependent recovery of the original high-energy phosphate resonance intensities was observed. These changes are qualitatively similar to those produced by ischemic inhibition of energy metabolism and are correlated with early histological features like vascular disruption, stasis within capillaries, and focal thrombosis. These results demonstrate that experimental HESW treatment of the NU-1 kidney tumor is effective in provoking a temporary reduction of both high-energy phosphate metabolism and tissue pH of the tumor. The data presented here strongly suggest that these effects are predominantly indirect by affecting tumor vascularity. Overall, this study shows that MRS is a powerful technique for longitudinal investigations of HESW-induced effects and can provide information about its mode of action.

Animals↗
PubMed1989

Broadband proton decoupling in human 31P NMR spectroscopy.

The limited chemical shift dispersion of in vivo 31P NMR spectra obtained at the relatively low field strengths used for human applications is the cause of poor spectral resolution. This makes it difficult to obtain accurate quantitative information from overlapping resonances, and interesting resonances may be obscured. At 1.5 T unresolved 1H-31P couplings contribute significantly to the linewidth of in vivo 31P NMR resonances. Therefore, proton decoupling can improve spectral resolution substantially, resulting in better resolved resonances and more reliable quantitative information. In this work it is shown that well resolved resonances of glycerophosphocholine, glycerophosphoethanolamine and phosphoethanolamine are obtained in 1H decoupled 31P NMR spectra of human muscle, brain, and liver. In spectra of the human heart it has been possible to resolve the myocardial Pi signal from the signals of 2,3-diphosphoglycerate from blood. With surface coils it is difficult to achieve broadband decoupling over the entire sensitive region of the coil by using conventional decoupling sequences. This problem has been overcome by applying a train of frequency modulated inversion pulses to achieve proper decoupling despite B2 inhomogeneity. Broadband 1H decoupling of 31P NMR spectra was possible without exceeding specific absorption rate guidelines.

Brain↗
PubMed1989

Broadband proton decoupled natural abundance 13C NMR spectroscopy of humans at 1.5 T.

The feasibility of broadband proton decoupled in vivo 13C NMR spectroscopy of humans at 1.5 T was explored. A dual surface coil set-up was used, comprising a circular 13C coil and a butterfly 1H decoupling coil placed at one third of its width away from the body. A calibration procedure was introduced to evaluate the specific absorption rate (SAR) in any gram of tissue for the inhomogeneous decoupling field generated by a surface coil. For the WALTZ-4 sequence it was demonstrated that broadband decoupled spectra of both subcutaneous adipose and underlying muscle or liver tissue could be obtained at 1.5 T without exceeding recommended maximum SAR values. Broadband decoupling caused an additional resolution enhancement ascribed to the removal of (1H-13C) long range couplings. Broadband proton decoupled spectra of subcutaneous adipose tissue were obtained in less than 10 min showing highly resolved and intense signals of fully relaxed carbon spin systems of triacylglycerols. Broadband proton decoupled 13C NMR spectra of calf muscle showed several resonances for metabolites resolved from triacylglycerol signals (e.g. C1-C5 of glycogen, C4 of histidine, aromatic and carbonyl carbons of aminoacids and N linked carbons of ethanolamine, choline and creatine). With an acquisition time of 20-30 min, the C1 glycogen signal was observed with a root mean square signal-to-noise ratio of about 15. Not only the glycogen C1 signal but also its C2-C6 signals could be monitored in dynamic studies. Finally broadband proton decoupled 13C spectra were obtained with signals from liver tissue (notably the carbons of glycogen).(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1988

In vivo 31P NMR studies of rat salivary glands at 6.3 tesla.

In vivo 31P NMR spectra of rat submandibular glands were obtained. The glands were exposed, leaving the neurovascular system intact, and placed in a solenoidal coil. Resonances of nine phosphate metabolites were identified in the spectra and metabolite concentrations were estimated from the corresponding integrals ([ATP] = 3.4 +/- 0.7 mM). Tissue pH, as deduced from the chemical shift of the inorganic phosphate resonance, was 7.26 (+/- 0.07). T1 relaxation times of ATP, phosphocreatine, inorganic phosphate, and phosphomonoester 31P spin systems were examined. The effect of hypoxia was followed as a function of time. 31P NMR spectra of the glands have also been obtained noninvasively by the use of a surface coil, adapted to the dimensions of the glands, and depth pulses.

Animals↗
PubMed1988

Alterations in relative phosphocreatine concentrations in preclinical mouse muscular dystrophy revealed by in vivo NMR.

Using in vivo 31P NMR spectroscopy, the early postnatal development of lower hindleg muscles of normal and dystrophic mice was investigated. Ratios of phosphocreatine and inorganic phosphate, and of phosphocreatine and ATP increased exponentially during normal postnatal growth and differentiation. In dystrophic skeletal muscles, however, the ratios were already considerably lower during the early postnatal period, before histopathological features were observed. The ratios remained lower, relative to normal muscles, at least into the young adult stage. A deficiency in the sequestering of creatine or a defect in the phosphocreatine shuttle is proposed to explain the pathological features observed in this disorder.

Animals↗
PubMed1986

Study of the interaction between uncharged yeast tRNAPhe and elongation factor Tu from Bacillus stearothermophilis.

Proton NMR studies are presented on the interaction of nonaminoacylated yeast tRNAPhe and elongation factor Tu X GTP from Bacillus stearothermophilis. From experiments in which transfer of magnetization is observed between proton spins of tRNA and the protein, it is concluded that complex formation takes place. Amino acid residues of the protein come into close contact with the base pair A5U68 and/or U52A62 of the acceptor T psi C limb of the tRNA molecule. From the line broadening of tRNA resonances, associated with complex formation, an association constant of 10(3)-10(4) M-1 is estimated. The NMR experiments do not monitor a significant conformational change of the tRNA molecule upon interaction with the protein. However, at times long after the onset of complex formation, spectral changes indicate that the upper part of the acceptor helix becomes distorted.

Base Composition↗
PubMed1986

Influence of the polyamines spermine and spermidine on yeast tRNAPhe as revealed from its imino proton NMR spectrum.

A comparison of imino proton NMR spectra of yeast tRNAPhe recorded at various solution conditions indicates, that polyamines have a limited effect on the structure of this tRNA molecule. Polyamines are found to catalyse the solvent exchange of several imino protons in yeast tRNAPhe not only of non hydrogen bonded imino protons, but also of imino protons of the GU and of some AU and tertiary base pairs. It is concluded that at low levels of catalysing components the exchange rates of the latter protons are not determined by the base pair lifetime. In the presence of high levels of spermidine the solvent exchange rates of imino protons of several base pairs in the molecule were assessed as a function of the temperature. Apparent activation energies derived from these rates were found to be less than 80 kJ/mol, which is indicative for (transient) independent opening of the corresponding base pairs. In the acceptor helix the GU base pair acts as a dynamic dislocation. The AU base pairs at one side of the GU base pair exhibit faster transient opening than the GC base pairs on the other side of this wobble pair. The base pairs m2GC10 and GC11 from the D stem and GC28 from the anticodon stem show relatively slow opening up to high temperatures. Model studies suggest that 1-methyladenosine, an element of tRNA itself, catalyses imino proton solvent exchange in a way similar to polyamines.

Base Composition↗
PubMed1985

Imino-proton resonances of yeast tRNAPhe studied by two-dimensional nuclear Overhauser enhancement spectroscopy.

Application of two-dimensional nuclear Overhauser enhancement (NOE) spectroscopy to yeast tRNAPhe in H2O solution demonstrates that all imino-proton resonances, related to the secondary structure, and nearly all imino proton resonances, originating from the tertiary structure, can be assigned efficiently by this method. The results corroborate the assignments of the imino-proton resonances of this tRNA as established previously by one-dimensional NOE experiments (only the assignment of base pairs G1 X C72 and C2 X G71 should be reversed). The advantages of two-dimensional NOE spectroscopy over one-dimensional NOE spectroscopy for the assignments of imino-proton resonances and the structure elucidation of tRNA are illustrated and discussed. Furthermore, the use of non-exchangeable proton resonances as probes of the molecular structure is explored.

Imines↗
PubMed1985

Interactions of some naturally occurring cations with phenylalanine and initiator tRNA from yeast as reflected by their thermal stability.

The thermal unfolding of phenylalanine and initiator tRNA from yeast was investigated over a broad range of solution conditions by differential ultraviolet absorption at 260 nm. Under most conditions, the initiator tRNA exhibits two clearly separated transitions in its differential melting curve which were assigned to unfolding of tertiary and secondary structure elements, respectively. The tertiary transition of this tRNA and the overall transition observed for tRNAPhe do not show a maximum in a curve of Tm values plotted as a function of [Na+]. Such a maximum is usually observed for other nucleic acids at about 1 M Na+. In the presence of 5 mM of the divalent cation Mg2+ (or Ca2+), an overall destabilization of the tRNAs is observed when increasing the sodium concentration. The largest fall in Tm (approximately 15 degrees C) is observed for the tertiary transition of the initiator tRNA. Among various cations tested the following efficiency in the overall stabilization of tRNAPhe is observed: spermine greater than spermidine greater than putrescine greater than Na+ (approximately NH4+). Mg2+ is most efficient at concentrations above 5 mM, but below this concentration spermine and spermidine appear to be more efficient. The same hierarchy in stabilizing power of the polyamines and Na+ is observed for both transitions of the initiator tRNA. However, when compared with Mg2+, the polyamines are far less capable of stabilizing the tertiary structure. In contrast, spermine and spermidine are slightly better than Mg2+ in stabilizing the secondary structure. At increasing concentrations of the polyvalent cations (at fixed [Na+] ) the Tm values of the tRNAs attain a constant value.

Calcium↗
PubMed1983

Nuclear magnetic resonance studies on yeast tRNAPhe. II. Assignment of the iminoproton resonances of the anticodon and T stem by means of nuclear Overhauser effect experiments at 500 MHz.

Resonances of the water exchangeable iminoprotons of the T and anticodon stem of yeast tRNAPhe were assigned by means of Nuclear Overhauser Effects (NOE's). Together with our previous assignments of iminoproton resonances from the acceptor and D stem (A. Heerschap, C.A.G. Haasnoot and C.W. Hilbers (1982) Nucleic Acids Res. 10, 6981-7000) the present results constitute a complete assignment of all resonances of iminoprotons involved in the secondary structure of yeast tRNAPhe with a reliability and spectral resolution not reached heretofore. Separate identification of the methylprotons in m5C40 and m5C49 was also possible due to specific NOE patterns in the lowfield part of the spectrum. Our experiments indicate that in solution the psi 39 residue in the anticodon stem is orientated in a syn conformation in contrast to the normally observed anti orientation of the uracil base in AU basepairs. Evidence is presented that in solution the acceptor stem is stacked upon the T stem. Furthermore, it turns out that in a similar way the anticodon stem forms a continuous stack with the D stem, but here the m2(2)G26 residue is located between the latter two stems (as is found in the X-ray crystal structure). The stacking of these stems is not strictly dependent on the presence of magnesium ions. NOE experiments show that these structural features are preserved when proceeding from a buffer with magnesium ions to a buffer without magnesium ions although differences in chemical shifts and NOE intensities indicate changes in the conformation of the tRNA.

Anticodon↗
PubMed1983

Nuclear magnetic resonance studies on yeast tRNAPhe. III. Assignments of the iminoproton resonances of the tertiary structure by means of nuclear Overhauser effect experiments at 500 MHz.

Resonances of the water exchangeable iminoprotons of the tertiary structure of yeast tRNAPhe were studied by experiments involving Nuclear Overhauser Effects (NOE's). Direct NOE evidence is presented for the assignment of all resonances of iminoprotons participating in tertiary basepairing (except that of G19C56 which was assigned by an elimination procedure). The present results in conjunction with our previous assignment of secondary iminoprotons constitute for the first time a complete spectral assignment of all iminoprotons participating in basepairing in yeast tRNAPhe. In addition we have been able to assign the non(internally) hydrogen bonded N1 proton of psi 55 as well as the N3 proton of this residue, which is one of the two iminoprotons hydrogen bonded to a phosphate group according to X-ray results. No evidence could be obtained for the existence in solution of the other iminoproton-phosphate interaction: that between U33 N3H and P36 located in the anticodon loop. Remarkable is the assignment of a resonance at 12.4 - 12.5 ppm to the iminoproton of the tertiary basepair T54m1A58. The resonance positions obtained for the iminoprotons of G18 (9.8 ppm) and m2(2)G26 (10.4 ppm) are surprisingly far upfield considering that these protons are involved in hydrogen bonds according to X-ray diffraction results. As far as reported by changes in chemical shifts of iminoproton resonances the main structural event induced by Mg++ ions takes place near the tertiary interactions U8A14 and G22m7G46.

Base Composition↗
PubMed1983

The solution structure of yeast tRNAPhe as studied by nuclear Overhauser effects in NMR.

Recently, the imino proton spectrum of yeast tRNAPhe has been assigned by means of the application of the nuclear Overhauser effect (NOE). In the present paper it will be shown that even for tRNA (MW 28000) connectivities between the imino proton spins can be observed using two-dimensional NOE spectroscopy. In this way the imino proton resonances of the D-stem region are assigned. The results are discussed in relation to those obtained by the classical one-dimensional nuclear Overhauser effect. It turns out that in 2D-NOE experiments connectivities from overlapping resonances can be observed which cannot be determined by one-dimensional Overhauser experiments. Moreover, the total assignment of the imino proton spectrum of yeast tRNAPhe is used to relate the three-dimensional crystal structure of the tRNA to its solution structure. It is shown that the principle elements of the X-ray structure, i.e. the hydrogen bonding network and the stacking of the stems upon one another, are also found in solution. This is true for the presence as well as for the absence of magnesium ions. However, in absence of magnesium ions the tRNA structure appears to differ in details from that in the presence of magnesium ions. Finally, the influence of the elongation factor Tu from B.stearothermophilus on the tRNA structure is discussed.

Binding Sites↗
PubMed1982

Nuclear magnetic resonance studies on yeast tRNAPhe I. Assignment of the iminoproton resonances of the acceptor and D stem by means of Nuclear Overhauser Effect experiments at 500 MHz.

Resonances of the water exchangeable iminoprotons of the acceptor and D stem of yeast tRNAPhe have been assigned by means of Nuclear Overhauser Effects (NOE's). Assignments were made for spectra recorded from tRNA dialysed against a buffer with 110 mM sodium and 5 mM magnesium ions and against a buffer with 430 mM sodium and no magnesium ions. Remarkable is the assignment of a resonance at 13.6 - 13.7 ppm to the iminoproton of C11G24. This assignment as well as those of G1C72, G3C70, U7A66, U12A23 and C13G22 are different from those made previously on the basis of less direct evidence. NOE experiments performed at 45 degrees C support the view that the D stem together with the tertiary interaction U8A14 is one of the most stable parts of the molecule in the presence of magnesium ions. A comparison of the spectra recorded under the two different buffer conditions shows that an excess of 320 mM sodium ions is not capable to force the tRNA in the same conformation as 5 mM magnesium ions can do.

Base Sequence↗