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D Leibfritz

Publications and source records attributed to D Leibfritz.

At least 109 records · Page 6Linked to original sources
PubMed1987

The in vivo contour plot. An improved representation of stimulus experiments.

The in vivo contour plot is a superior representation of the data from stimulus experiments. Its performance is illustrated by four examples, viz., necrosis of a superfused rat heart, anoxia on perfused mouse liver, ischemiae on Langendorff heart in the presence and absence of a Ca antagonist, and the internal stimulus of the cardiac cycle. The in vivo contour plot visualizes line intensities (metabolite concentrations), line positions (pH), and linewidths, as well as the time derivatives of these parameters in any available number of spectra.

Animals↗
PubMed1976

Structural and membrane modifying properties of suzukacillin, a peptide antibiotic related to alamethicin. Part A. Sequence and conformation.

The primary structure and conformation of the polypeptide antibiotic suzukacillin A are investigated. Suzukacillin A is isolated from the Trichoderma viride strain 1037 and exhibits membrane modifying and lysing properties similar to those of alamethicin. A combined gas chromatographic mass spectrometric analysis of the trifluoroacetylated peptide methyl esters of partial hydrolysates revealed a tentative sequence of 23 residues including 10 2-methylalanines and one phenylalaninol, which shows many fragments known from alamethicin: Ac-Aib-Pro-Val-Aib-Val-Ala-Aib-Ala-Aib-Aib-Gln-Aib-Leu-Aib-Gly-Leu-Aib-Pro-Val-Aib-Aib-Glu(Pheol)-Gln-OH. All chiral amino acids and phenylalainol have L-configuration. Ultraviolet and infrared spectroscopy, circular dichroism in various solvents and in particular 13C nuclear magnetic resonance have been used for a comparative study of suzukacillin with alamethicin. Suzukacillin has a partially alpha-helical structure and the helix content increases largely from polar to lipophilic solvents. Suzukacillin aggregates more strongly than alamethicin in aqueous medis due to a longer alpha-helical part and higher number of aliphatic residues. A part of the alpha-helix is exceptionally stabilized due to 2-methylalanine residues shielding the peptide bonds from interactions with polar solvents. In lipophilic solvents and lecithin vesicles particularly large temperature induced reductions of the high alpha-helix content are found for alamethicin. Suzukacillin shows similar temperature coefficients in lipophilic media, however, in contrast to alamethicin a more linear change in intensity of the Cotton effects is observed.

Alamethicin↗
PubMed1976

Structural and membrane modifying porperties of suzukacillin, a peptide antibiotic related to alamethicin. Part B. Pore formation in black lipid films.

Suzukacillin, a polypeptide consisting of presumably 23 amino acids and 1 phenylalaninol, is produced by a Trichoderma viride strain No. 1037 and it can be isolated from the culture medium. It shows membrane-modifying properties similar to those of alamethicin. Discrete condustance fluctuations indicate the formation of oligomer pores of varying diameter. On the basis of voltage jump relaxation experiments evidence is given that the dimer is the nucleation state from which pore formation starts and the oligomer disappears. According to the voltage-current characteristics, voltage-dependent and voltage-independent conductances are observed. A slow process is involved, which can be interpreted as a change in the equilibrium distribution between different conformations of the suzukacillin monomer at the membrane interphase. This change results from its interaction with the lipid matrix. Differences in experimental observations between suzukacillin and alamethicin are attributed to the relatively larger alpha-helix and higher number of aliphatic side chains of the suzukacillin monomer and to a more intense interaction with the lipid membrane. This leads to a higher probability of forming dimers from monomers and to the occurrence of "inactivation".

Alamethicin↗
PubMed1973

Nuclear Magnetic Resonance Shift Reagents: Abnormal C Shifts Produced by Complexation of Lanthanide Chelates with Saturated Amines and n-Butyl Isocyanide.

Lanthanide-induced shfits of (13)C nuclear magnetic resonances are reported for several amines and n-butyl isocyanide. Contact contributions to such shifts, especially of beta carbons, are clearly important for the chelates of Eu(+3) and Pr(+3). The importance of contact terms is shown to change in a rather predictable manner with the structure of the amine.

Journal Article↗
PubMedDate not supplied

A 13C NMR study on fluxes into the TCA cycle of neuronal and glial tumor cell lines and primary cells.

Two tumor cell lines (C6 glioma and N1E-115 neuroblastoma), primary glia and primary neurons (from rat) were incubated with 2-13C-pyruvate and 3-13C-pyruvate in culture dishes. 13C NMR spectra of the cell extracts were used to determine the ratio of pyruvate carboxylase to pyruvate dehydrogenase activity. Pyruvate carboxylase activity was found higher in primary glia cells than in neurons. Glial cells synthesized more amino acids, ie, their TCA cycle was used to a larger extent for biosynthesis than is the case of neurons, where it is preferentially used for the energy metabolism.

Animals↗
PubMedDate not supplied

Pre-operative localized in vivo proton spectroscopy in cerebral tumors at 4.0 Tesla--first results.

Sixteen patients with prediagnosed cerebral lesions were studied with stimulated echo localized 1H-spectroscopy at 4 Tesla. Initially, CT cerebral angiography and MR investigation at 1.5 Tesla were performed. After selecting a patient and receiving his agreement the high field examination started with the acquisition of an MR image of the known tumor at 4 Tesla using head or surface coil. 1H-spectroscopy was performed by selectively exciting a cubic volume between 8 to 20 cubic centimeters in the center of the tumor, in one case below 4 ccm (pinealoma). If possible, in a second examination the corresponding opposite side of the brain was studied. The extirpation of the tumor followed during the next days. Macroscopic aspects, histology and grading of the investigated lesions were determined. In some cases, specimens of the tumors were cooled in cooking salt solution and in liquid nitrogen, respectively, in order to perform in vitro proton MRS at 8.4 Tesla. The evaluable in vivo spectra showed good resolution and significant differences between corresponding cerebral areas with and without tumor as well as between different types of tumor histologies like medulloblastoma, astrocytoma and meningeomas. Often a good correspondence between in vivo and in vitro spectroscopy was seen. No clinically relevant side effects or complications were observed during the in vivo high field examination.

Adult↗
PubMedDate not supplied

Inversion recovery snapshot FLASH MR imaging.

Snapshot fast low angle shot (FLASH) magnetic resonance (MR) imaging techniques have been developed to enable real time imaging of MR parameters. The method is based on a 64 x 128 FLASH tomogram acquired within less than 200 ms. This work describes snapshot FLASH MR using a single 180 degrees pulse prior to the acquisition of a series of FLASH images. The experiment creates continuous dynamic inversion recovery (IR) T1 contrast in successive images. The total acquisition time of 16 images displaying the IR behavior is less than 4 s. Representative snapshot FLASH IR MR images of the abdomen of healthy rats and of an implanted hepatic tumor are illustrated.

Animals↗
PubMedDate not supplied

Effects of ammonia exposition on glioma cells: changes in cell volume and organic osmolytes studied by diffusion-weighted and high-resolution NMR spectroscopy.

NH(4)Cl (10 mM) caused a sustained increase in the cell volume in immobilized, perfused F98 glioma cells to approx. 125% of control after 3 h, as measured by diffusion-weighted (1)H NMR spectroscopy. Concomitantly, the glutamine (Gln) concentration increased by 130%, accompanied by a marked decrease in cytosolic osmolytes, i.e. myo-inositol and taurine, determined from (1)H NMR spectra of PCA extracts. Inhibition of Gln synthetase partially prevented the increase in water content. While losses of organic osmolytes are also observed under hypotonic conditions, the rapid cell swelling is followed by the regulatory cell volume decrease (RVD), and is accompanied by decreased cytosolic Gln. We suggest that the rise in intracellular osmolarity, which is attributed to NH(4)Cl metabolism to Gln, but also to alanine (Ala), is not compensated by the release of other osmolytes, and causes cell swelling without RVD.

Alanine↗
PubMedDate not supplied

31P NMR studies on perfused liver from mouse with chronic ethanol ingestion.

Changes in the levels of phosphate metabolites as affected by acute ethanol administration and chronic ethanol ingestion were investigated in perfused mouse liver by 31P NMR spectroscopy. Acute ethanol administration decreases intracellular Pi and the Pi/ATP ratio, and increases phosphomonoester levels in normal-fed animals. No such change was observed in the liver from ethanol-fed mice. Chronic ethanol ingestion renders the liver more prone to ischemia-induced changes in ATP, intracellular Pi and phosphomonoesters. The Pi/ATP ratio increases fivefold in control mice and fourfold in alcohol-fed mice when ischemia is induced in the presence of ethanol. Intracellular pH of 7.45 +/- 0.05 is not affected by ethanol perfusion. Cellular acidosis resulting from ischemia in the presence or absence of alcohol was similar. However, longer period of ischemia leads to an additional 0.11 unit drop in pH in the presence of ethanol.

Adenosine Diphosphate↗
PubMedDate not supplied

Changes of intracellular calcium, fatty acids and phospholipids during miltefosine-induced apoptosis monitored by fluorescence- and 13C NMR-spectroscopy.

The alkylphosphocholine Miltefosine (hexadecylphosphocholine, HePC) induces apoptosis in human epithelial KB cells, whereas no such effect can be observed in a resistant clone (KBres). Its mode of action is mediated via the cell membrane, whereas the mechanism is still widely unknown. The use of various spectroscopic methods (fluorescence spectroscopy with Fura-2/AM on viable cells, 13C NMR spectroscopy on lipid extracts) reveals osmotic and metabolic changes in HePC treated sensitive cells. Intracellular free Ca(2+)-concentration increased over 300% of control in apoptotic cells, whereas KBres cells showed only a minor increase and no morphological response typical for apoptosis. The Ca(2+)-influx was mediated via calcium channels in the cell membrane. The HePC-induced influx is prevented by Gd3+, which blocks those calcium channels. Cells, grown in Ca(2+)-free medium, showed no apoptotic behaviour after treatment with HePC. If apoptosis was induced, an increased fatty acid and subsequent phospholipid biosynthesis was observed. This effect seems to be a specific marker of apoptosis in KB cells.

Antineoplastic Agents↗
PubMedDate not supplied

Characterization of CNS lesions by using high-resolution 1H MR spectroscopy of CSF: preliminary results.

Sixty-six samples of CSF from 66 patients with a variety of diseases, including tumors, arteriovenous malformations, aneurysms, brain infarctions, and lumbar back pain, were studied with 1H MR spectroscopy at 360 MHz. 1H MR spectroscopy offers a simple means to obtain fast information about different metabolites simultaneously. As compared with the control group, which consisted of 19 CSF samples from the same group of 66 patients, but from individuals who had no abnormal findings on neurologic examination, common clinicochemical tests, or neuroradiologic studies, our preliminary results suggest that tumors and hemorrhages may be differentiated by 1H MR spectroscopy. MR peak intensities relative to lactate peak intensity were used as variables in a statistical analysis to determine the significance of individual resonance intensities in predicting CNS abnormalities. The most important factors for diagnosis were analyzed by means of a multivariate general linear hypothesis and a principal component method. The most important factors for predicting CNS abnormalities in the studied diseases were creatinine, glucose, creatine, citrate, protein content, glutamine, amount of cells, and valine. By using this model for discriminant analysis, we could predict hemorrhages correctly in 88% of cases and tumors in 75% of cases. All samples of controls were determined correctly. In cases of brain infarctions, different signals were observed, which may lead to further characterization of such lesions. 1H MR spectroscopy may offer a simple means for further characterizing CNS lesions. However, this needs confirmation by a prospective study, which would include a larger patient population with different diseases.

Central Nervous System Diseases↗
PubMedDate not supplied

An introduction to the potential of 1H-, 31P- and 13C-NMR-spectroscopy.

Multinuclear NMR spectroscopy (1H, 13C, 31P) of biological samples reflects their metabolic composition. The analysis of high field and high resolution spectra of body fluids, cell and biopsy extracts requires no separation of a complex mixture into individual metabolites. Pattern recognition methods can be used to classify normal and pathological samples. Stable isotope enriched precursors are used to follow-up biochemical pathways and metabolic trafficking demonstrated for the lipid biosynthesis. Finally, volume selective in vivo spectroscopy or spectroscopic imaging depicts acute and time dependent metabolic events noninvasively in intact tissue within a few minutes.

Animals↗
PubMedDate not supplied

Combined extraction techniques of tumour cells and lipid/phospholipid assignment by two dimensional NMR spectroscopy.

As the cell membranes are one of the targets of drug treatment in cancer cells, their membrane composition and variations in this composition need to be analyzed. Gradient selected 2D-NMR inverse heteronuclear chemical shift correlations are have described, which offer optimum sensitivity combined with a high reliability for unequivocal signal assignment in proton, carbon and phosphorous spectra, concerning neutral lipids and in particular phospholipids. Additionally, an extraction procedure is presented to extract subsequently the water soluble (PCA extract) and lipophilic metabolites (chloroform/methanol extract) from the same cell batch.

Humans↗