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Biomedical subjects

F Sasse

Publications and source records attributed to F Sasse.

17 recordsLinked to original sources
PubMed2001

New natural epothilones from Sorangium cellulosum, strains So ce90/B2 and So ce90/D13: isolation, structure elucidation, and SAR studies.

In addition to epothilones A (1) and B (2), 37 natural epothilone variants and epothilone-related compounds were isolated from the culture broth of a 700 L fermentation of Sorangium cellulosum, strain So ce90/B2. Of these, only the 12,13-desoxyepothilones, epothilone C (14) and D (15), were produced in significant amounts (3-6 mg/L); the 21-hydroxy derivatives and epothilones E (3) and F (4), in low and variable amounts due to further degradation by the producing organism. Most of the other epothilone variants were produced only in 1-100 microg/L amounts. The new compounds are very similar in structure to the parent compounds 1, 2 and 14, 15 and are presumably the result of the imperfect selectivity of the biosynthetic enzymes for acetate and propionate. Further, epothilones containing an oxazole moiety (10-13) in the side chain instead of a thiazole as well as ring-expanded 18-membered macrolides, epothilones I (30-35), and a ring contracted 14-membered macrolide, epothilone K (36), were found as very minor metabolites. The mutant strain, So ce90/D13, instead of macrolactones, produced short-chain carboxylic acids 40, 41, and 42 bearing the characteristic thiazole side chain. The structures of the new epothilones were elucidated on the basis of comprehensive NMR and MS data. The new epothilone variants were tested in a cytotoxicity assay with mouse fibroblasts (cell line L929), and structure-activity relationships were established. Several new natural epothilones showed activity comparable to 1 and 2, but in no case exceeded that of 2.

Animals↗
PubMed2000

Tubulysins, new cytostatic peptides from myxobacteria acting on microtubuli. Production, isolation, physico-chemical and biological properties.

New cytostatic compounds, tubulysins, were isolated from the culture broth of strains of the myxobacteria Archangium gephyra and Angiococcus disciformis. The compounds are peptides partly consisting of unusual amino acids and are distantly related to the dolastatins. The tubulysins were not active against bacteria and only little against fungi, but showed high cytostatic activity against mammalian cell lines with IC50 values in the picomolar range. An incubation with 50 ng/ml tubulysin A led to a complete disappearance of the microtubuli network of the cells within 24 hours. The more active tubulysin D induced multipolar spindles: At 0.5 ng/ml all mitotic cells showed more than four spindle poles.

Animals↗
PubMed1999

Effects of rhizopodin and latrunculin B on the morphology and on the actin cytoskeleton of mammalian cells.

The effects of the novel myxobacterial compound rhizopodin on mammalian cells were studied and compared with those of latrunculin B. Both substances induced adherently growing L929 mouse fibroblasts and PtK2 potoroo kidney cells to produce long, narrow, branched extensions or runners. Rhizopodin was more efficient than latrunculin B in that respect (minimal inhibitory concentration with L929 cells 5 nM vs 50 nM), and, in contrast to latrunculin B, its effects were permanent. Rhizopodin-treated cells became much larger than normal cells and were multinucleate, yet stayed alive and biochemically active for several weeks. Latrunculin B-treated cells returned to a quasi-normal state within 3-4 days. But latrunculin B acted faster, with the first effects becoming visible almost immediately upon the addition of the drug, while the first rhizopodin effects were seen 10 min later. Both substances caused reorganization of the actin cytoskeleton. When 100 nM rhizopodin was added to PtK2 cells, the stress fibers began to decay after just 10 min and had disappeared completely after about 3 h. Later there was a gradual restitution of F-actin. Long F-actin fibers were seen within the runners, and only there; in fact, these fibers may be responsible for the development and extension of the runners. The microtubuli network adjusted itself to the new cell morphology, but was not directly impaired by the compound.

Actins↗
PubMed1999

Melithiazols, new beta-methoxyacrylate inhibitors of the respiratory chain isolated from myxobacteria. Production, isolation, physico-chemical and biological properties.

New antibiotic compounds, melithiazols, were isolated from the culture broth of strains of the myxobacteria Melittangium lichenicola, Archangium gephyra, and Myxococcus stipitatus. The compounds belong to the group of beta-methoxyacrylate (MOA) inhibitors and are related to the myxothiazols. The melithiazols show high antifungal activity, but are less toxic than myxothiazol A and its methyl ester in a growth inhibition assay with mouse cell cultures. The melithiazols inhibit NADH oxidation by submitochondrial particles from beef heart. Melithiazol A blocks the electron transport within the bc1-segment (complex III) and causes a red shift in the reduced spectrum of cytochrome b.

Acrylates↗
PubMed1998

The chondramides: cytostatic agents from myxobacteria acting on the actin cytoskeleton.

BACKGROUND: Chondramides are cyclodepsipeptides produced by strains of the myxobacterium, Chondromyces crocatus. These peptides, which have been reported to inhibit yeast and mammalian cell proliferation, are related to jasplakinolide, which has been isolated from marine sponges of the genus Jaspis and has been shown to interfere with the actin cytoskeleton (a structural component of cells that helps maintain their shape and is involved in processes, such as cell division and cell locomotion). We studied the effects of the chondramides (A, B, C, and D) on tumor cell growth, on cytoskeletal structure, and on actin polymerization in vitro and compared these effects with those of cytochalasin D and jasplakinolide. METHODS: Cell proliferation was measured by means of tetrazolium salt reduction assays. Effects on the cytoskeleton were studied by use of fluorescence techniques, and actin polymerization in vitro was measured by means of viscosimetry. RESULTS: Proliferation of tested tumor cell lines was inhibited by the chondramides. Concentrations that inhibited proliferation by 50% (IC50 values) ranged from 3 to 85 nM and were of the same order of magnitude as those found for cytochalasin D and jasplakinolide. Fluorescence staining of potoroo cells incubated with chondramides A and B showed that organization of the actin cytoskeleton was disrupted; however, the microtubule system was not affected. Viscosimetric measurement showed that, depending on the experimental conditions, chondramide A induced or accelerated actin polymerization in vitro. CONCLUSION: The chondramides--unlike jasplakinolide--can be produced in large amounts by fermentation, and, similar to jasplakinolide, they appear to have antiproliferative activity against carcinoma cell lines by targeting the actin cytoskeleton.

Actins↗
PubMed1998

Apicularens A and B, new cytostatic macrolides from Chondromyces species (myxobacteria): production, physico-chemical and biological properties.

A novel macrolide, apicularen A, was produced by several species of the genus Chondromyces. Initially it was discovered by bioassay-guided RP-HPLC-fractionation of culture extracts of Chondromyces robustus, strain Cm a13. Apicularen A showed no antimicrobial activity, but was highly cytotoxic for cultivated human and animal cells, with IC50 values ranging between 0.1 and 3 ng/ml. A cometabolite of apicularen A, the N-acetylglucosamine glycoside apicularen B, was distinctly less cytotoxic with IC50 values between 0.2 and 1.2 microg/ml, and showed weak activity against a few Gram-positive bacteria. Apicularen A is chemically closely related to the salicylihalamides A and B from the marine sponge Haliclona sp.

Animals↗
PubMed1997

Epothilone B stabilizes microtubuli of macrophages like taxol without showing taxol-like endotoxin activity.

Epothilones are a new class of potential antitumor compounds that were isolated from the myxobacterium Sorangium cellulosum. Epothilones have effects on the cytoskeleton similar to those of the antineoplastic drug Taxol. Both compounds inhibit cell proliferation by stabilizing microtubuli, and they compete for the same binding site. In addition, Taxol displays endotoxin-like properties in that it activates macrophages to synthesize proinflammatory cytokines and nitric oxide. We measured nitric oxide release by IFN-gamma-treated murine macrophages as an indicator of macrophage activation by epothilone B. Although epothilone B showed the expected effects on the microtubuli, there was no indication of macrophage stimulatory activity by epothilone B, nor did epothilone B inhibit lipopolysaccharide-mediated nitric oxide release. We conclude that, unlike Taxol, epothilone-mediated microtubuli stabilization does not trigger endotoxin-signaling pathways. Moreover, because the endotoxin-like activity of Taxol may be the cause of some nonhematological clinical side effects, it is to be expected that such effects may not occur with epothilones.

Animals↗
PubMed1995

Chondramides A approximately D, new antifungal and cytostatic depsipeptides from Chondromyces crocatus (myxobacteria). Production, physico-chemical and biological properties.

Novel depsipeptides, named chondramides were produced at levels up to 4.3 mg/liter by several myxobacteria of the genus Chondromyces. The compounds are structurally closely related to jaspamide/jasplakinolide from marine sponges of the genus Jaspis. Initially the chondramides were detected in acetone extracts of the biomass of Chondromyces crocatus, strain Cm c2. So far, four structural variants could be characterized, the chondramides A approximately D. They inhibited the growth of a few yeasts and showed high cytostatic activity against cultivated human and animal cells.

Animals↗
PubMed1995

Gephyronic acid, a novel inhibitor of eukaryotic protein synthesis from Archangium gephyra (myxobacteria). Production, isolation, physico-chemical and biological properties, and mechanism of action.

A new antibiotic compound, gephyronic acid was isolated from the culture broth of the myxobacterium, Archangium gephyra strain Ar 3895. Up to 3 mg/liter was produced during the logarithmic and stationary growth phase. The compound is an aliphatic acid, which tends to form a hemiacetal. Both forms inhibited growth of yeasts and molds (MIC 1-25 micrograms/ml) and had a cytostatic effect on mammalian cell cultures (IC50 10-60 ng/ml). Gephyronic acid is a specific inhibitor of eukaryotic protein synthesis showing an IC50 of 1-2 x 10(-7) mol/liter in an in vitro translation assay.

Animals↗
PubMed1993

Rhizopodin, a new compound from Myxococcus stipitatus (myxobacteria) causes formation of rhizopodia-like structures in animal cell cultures. Production, isolation, physico-chemical and biological properties.

A new cytostatic compound, rhizopodin, was isolated from the culture broth of the myxobacterium, Myxococcus stipitatus. The compound inhibited growth of various animal cell cultures without killing the cells. The ID50, measured by an MTT assay, was 12 approximately 30 ng/ml, depending on the cell line. Especially cells growing fibroblast-like showed typical morphological changes. They became larger and within hour formed long branching and reticular runners. These morphological changes were irreversible. Rhizopodin suppresses bleb formation in K-562 cells, and therefore could act by interacting with protein phosphorylation.

Animals↗
PubMed1992

Effects of hypocapnia on canine spinal, subcortical, and cortical somatosensory-evoked potentials during isoflurane anesthesia.

Although hyperventilation with hypocapnia is frequently used in the management of neurosurgical patients in whom sensory-evoked potentials may be monitored, the effects of hypocapnia on evoked potentials have not been described with precision. In the present experiment, the effects of randomized arterial carbon dioxide tensions of 20, 25, 30, and 35 mm Hg on spinal, subcortical, and cortical somatosensory-evoked potentials (SEPs) were measured in dogs anesthetized with 1.40% isoflurane. Other variables known to affect the SEP (temperature, blood pressure, and arterial oxygen tension) were stable throughout the experiment. Hypocapnia caused reductions in the latencies of the early peaks of the spinal and subcortical SEPs. These differences were small, consisting of a 2% shortening of latency at 20 mm Hg carbon dioxide tension when compared with 35 mm Hg. No changes were detected in the later subcortical and cortical latencies. SEP amplitudes were also unchanged. These results in a controlled animal study corroborate the direction and magnitude of changes due to hypocapnia observed by other investigators in surgical patients. The magnitude of the changes indicates that SEP monitoring sensitivity is not compromised by clinically useful levels of induced hypocapnia during isoflurane anesthesia. Because hypocapnia may produce small SEP changes, baseline recordings should be acquired prior to initiation of hyperventilation. It is not warranted, however, to impute a severe deterioration of the SEP to hypocapnia alone, and causes must be sought elsewhere in a patient's status and management.

Analysis of Variance↗
PubMed1988

Effects of halothane dose and stimulus rate on canine spinal, far-field and near-field somatosensory evoked potentials.

Evidence that canine spinal, far-field and near-field somatosensory evoked potentials resemble those recorded in humans and other species has been presented, and the vulnerability of each component to varying depths of halothane anesthesia is reported. Lumbar spinal peak latencies are not affected by halothane dose, but the negative peak is significantly prolonged by rapid rates of stimulation. Elevated stimulus rates and halothane doses reduce lumbar spinal cord potential amplitudes. Early far-field cephalic components are refractory to halothane. Late far-field components and near-field cortical potentials are substantially altered by increments in halothane dose. Both near-field and far-field responses are more readily identified in vertex-neck than vertex-brow derivations. Early far-field somatosensory evoked potentials recorded from vertex to neck, together with lumbar spinal cord potentials, may be the preferred monitoring technique when the use of halothane anesthesia is desired. Rapid rates of stimulation may facilitate earlier recognition of cord dysfunction, but supplement rather than replace baseline recordings at slow stimulus rates.

Animals↗
PubMed1982

Accumulation of beta-Carboline Alkaloids and Serotonin by Cell Cultures of Peganum harmala L: I. CORRELATION BETWEEN PLANTS AND CELL CULTURES AND INFLUENCE OF MEDIUM CONSTITUENTS.

A number of cell cultures of Peganum harmala were initiated to check for a correlation between the harman alkaloid content of seedlings and cell lines derived therefrom. Despite a poor correlation between callus or suspension culture lines and parent plants, the mean alkaloid contents of strains derived from seedlings with higher alkaloid yields were nevertheless higher than the mean contents of strains derived from low yield plants. Generally, alkaloid accumulation decreased with the numbers of transfers. By permanent visual selection for fluorescent areas of the calluses, however, a mean content of 0.1% harman alkaloids and 0.1% serotonin could be maintained, which was 10 times higher than in unselected callus cultures.The effects of medium constituents on harman alkaloid and serotonin accumulation were measured for a low yielding, faster growing suspension culture strain and a slowly growing, but high yielding cell line. This led to the development of a production medium without 2,4-dichlorophenoxyacetic acid and phosphate, and with Ca, Mg, and nitrate as sole macronutrients. When this production medium was used, the accumulation of harman alkaloids and serotonin was increased from 0.1 to 1% in the low yielding cell line and from 1 to 2% in the high yielding strain.

Journal Article↗
PubMed1979

Use of positive airway pressure without endotracheal intubation.

Continuous positive airway pressure (CPAP) and expiratory positive airway pressure (E-PAP) may be used safely without endotracheal intubation in patients with acute respiratory failure when strict selection criteria are adhered to. The therapy should be titrated to reduce intrapulmonary shunting, improve PaO2, and reduce FIO2. Other considerations include balancing oxygen consumption against cardiac output and oxygen transport. Absolute or relative indications for abandoning the technique and using endotracheal intubation with mechanical ventilatory support include unrelenting hypoxia, patient exhaustion, rising PaCO2, development of metabolic acidosis, presence of ventricular arrhythmias, and inability to protect the airway.

Acute Disease↗
PubMedDate not supplied

Formation of beta-peltatin-A methyl ether and coniferin by root cultures of Linum flavum.

Extracts of root cultures of Linum flavum contained high cytotoxic activity due to the presence of 1% beta-peltatin-A methyl ether of the dry mass. During chromatographic analysis of the cell extracts, coniferin was identified as the major uv-absorbing but noncytotoxic constituent with levels of up to 3% of the dry mass. Growth, culture appearance, and product accumulation varied greatly with the 2,4-D concentration in the medium.

2,4-Dichlorophenoxyacetic Acid↗