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M Iten

Publications and source records attributed to M Iten.

7 recordsLinked to original sources

Signalling of abscisic acid to regulate plant growth.

Abscisic acid (ABA) mediated growth control is a fundamental response of plants to adverse environmental cues. The linkage between ABA perception and growth control is currently being unravelled by using different experimental approaches such as mutant analysis and microinjection experiments. So far, two protein phosphatases, ABI1 and ABI2, cADPR, pH, and Ca2+ have been identified as main components of the ABA signalling pathway. Here, the ABA signal transduction pathway is compared to signalling cascades from yeast and mammalian cells. A model for a bifurcated ABA signal transduction pathway exerting a positive and negative control mechanism is proposed.

Abscisic Acid↗

[Fatigue, general weakness, subcutaneous nodules].

A 58 year old female patient presented with subcutaneous nodules (adenocarcinoma on cytology) and general symptoms as first symptoms of advanced metastasizing cancer of the breast. The patient succumbed to metastatic disease and terminal bronchopneumonia a few months later. The path to diagnosis in a situation with diffusely metastasizing cancer, the differential diagnosis during evaluation and the rationale for the choice of investigations in a patient with far advanced metastasizing cancer but unknown primary site are discussed.

Adenocarcinoma↗

The Alamar Blue assay to determine drug sensitivity of African trypanosomes (T.b. rhodesiense and T.b. gambiense) in vitro.

Alamar Blue, an indicator for metabolic cell function, was evaluated as a fluorescent and as a colorimetric dye in drug sensitivity assays for human pathogenic African trypanosomes, Trypanosoma brucei rhodesiense and T.b. gambiense. The experimental conditions were adjusted to find those where the relationship between trypanosome number and Alamar Blue signal was linear over the widest possible range. Fluorescent signals correlated to trypanosome numbers from 10(4) trypanosomes/ml (T.b. rhodesiense) and 10(5) trypanosomes/ml (T.b. gambiense) up to 2-3 x 10(6) trypanosomes/ml when trypanosomes were incubated for 2 h with 10% Alamar Blue. Trypanocidal activity of common drugs (melarsoprol, DFMO, suramin, pentamidine and diminazene aceturate) was determined employing this assay. The IC50 values obtained were comparable to those obtained with another fluorochrome, BCECF-AM. The Alamar Blue assay can be applied for drug screening, since it is simple, reproducible and economical. The assay can also be used in field sites with less equipped laboratories, because in addition to fluorometric endpoint determination, a colorimetric reading is possible.

Animals↗

Susceptibility of Ugandan Trypanosoma brucei rhodesiense isolated from man and animal reservoirs to diminazene, isometamidium and melarsoprol.

Thirty-six Trypanosoma brucei spp. stocks isolated from man and domestic animals in south-east Uganda were studied for susceptibility to diminazene, isometamidium and melarsoprol in vitro. All stocks were susceptible to melarsoprol. One T.b. rhodesiense stock isolated from a sleeping sickness patient showed reduced susceptibility to the veterinary drugs diminazene and isometamidium. More than 100 ng/ml diminazene or 0.78 ng/ml isometamidium were required to eliminate that stock during 10 days drug exposure. In contrast, the remaining stocks were eliminated by 0.8-6.3 ng/ml diminazene and 0.01-0.20 ng/ml isometamidium. Clones derived from the resistant T. b. rhodesiense stock showed reduced susceptibility to isometamidium and diminazene comparable to the parental population. Control of sleeping sickness by treatment of the animal reservoir could, therefore, face serious problems since drug-resistant stocks as reported here would most likely not be eliminated by recommended doses of diminazene and isometamidium.

Animals↗

Alterations in ornithine decarboxylase characteristics account for tolerance of Trypanosoma brucei rhodesiense to D,L-alpha-difluoromethylornithine.

Ornithine decarboxylase (ODC), the target enzyme of D,L-alpha-difluoromethylornithine (DFMO), was investigated in four DFMO-tolerant Trypanosoma brucei rhodesiense isolates from East Africa and two DFMO-susceptible T. b. gambiense isolates from West Africa. Neither drug uptake nor inhibition of ODC activity by DFMO in cellular extracts differed in the two trypanosome subspecies. However, the specific ODC activity of the cellular extracts was three times as high in T. b. rhodesiense isolates as in T. b. gambiense isolates. Furthermore, a significant difference in the turnover rate of ODC was observed. The time required to induce a 50% reduction of T. b. rhodesiense ODC activity under cycloheximide pressure (tentative half-life) was about 4.3 h, whereas that required for T. b. gambiense ODC was longer than 18 h. We concluded that the higher specific ODC activity and faster enzyme turnover contributed to a substantial degree to the DFMO tolerance observed in the East African T. b. rhodesiense isolates.

Animals↗

Innate lack of susceptibility of Ugandan Trypanosoma brucei rhodesiense to DL-alpha-difluoromethylornithine (DFMO).

Trypanosoma brucei rhodesiense isolates from South East Uganda were characterized for susceptibility to the drugs suramin, nifurtimox, melarsoprol and DL-alpha-difluoromethylornithine (DFMO). Two different assays were used to determine the drug susceptibility of the field isolates: the [3H]hypoxanthine incorporation assay (24 hours) and the long term viability assay (10 days). All trypanosome stocks were susceptible to suramin and nifurtimox. Differences in the susceptibility to melarsoprol were observed in the [3H]hypoxanthine incorporation assay, but could not be confirmed in the long term viability assay. All T. b. rhodesiense stocks were found in vitro to have innate tolerance to DFMO, under conditions where T. b. gambiense stocks from West Africa were susceptible to the drug. Ugandan T. b. rhodesiense stocks did respond to 25-100 micrograms/ml after 10 days of drug exposure, but the DFMO level reached in cerebrospinal fluid during treatment is only 16.3 +/- 7.8 micrograms/ml. Therefore, DFMO is not an appropriate alternative or backup drug for treatment of Rhodesian sleeping sickness in Uganda.

Animals↗

Receptors and signalling components of plant hormones.

Recent advances in understanding plant hormonal signalling has resulted in the identification of a variety of signalling components including receptor kinases with homology to the bacterial two component system as well as serine/threonine kinases and protein phosphatases. In addition, the existence of MAP kinase pathways in plants indicates a similar role of these signalling cascades in the relay of exogenous signals into the nucleus as has been disclosed in animal cells. The emerging signalling pathways of the plant hormone abscisic acid and ethylene are presented.

Abscisic Acid↗