Biomedical subjects

F Linn

Publications and source records attributed to F Linn.

9 recordsLinked to original sources

PubMed1992

Endogenous and environmental factors influence 35S promoter methylation of a maize A1 gene construct in transgenic petunia and its colour phenotype.

30,000 transgenic petunia plants carrying a single copy of the maize A1 gene, encoding a dihydroflavonol reductase, which confers a salmon red flower colour phenotype on the petunia plant, were grown in a field test. During the growing season plants with flowers deviating from this salmon red colour, such as those showing white or variegated phenotypes and plants with flowers exhibiting only weak pigmentation were observed with varying frequencies. While four white flowering plants were shown at the molecular level to be mutants in which part of the A1 gene had been deleted, other white flowering plants, as well as 13 representative plants tested out of a total of 57 variegated individuals were not mutants but rather showed hypermethylation of the 35S promoter directing A1 gene expression. This was in contrast to the homogeneous fully red flowering plants in which no methylation of the 35S promoter was observed. While blossoms on plants flowering early in the season were predominantly red, later flowers on the same plants showed weaker coloration. Once again the reduction of the A1-specific phenotype correlated with the methylation of the 35S promoter. This variation in coloration seems to be dependent not only on exogenous but also on endogenous factors such as the age of the parental plant from which the seed was derived or the time at which crosses were made.

Alcohol Oxidoreductases↗

PubMed1990

Epigenetic changes in the expression of the maize A1 gene in Petunia hybrida: role of numbers of integrated gene copies and state of methylation.

The Petunia hybrida mutant RL01 is white flowering due to a genetic block in the anthocyanin pathway. The introduction of the maize A1 cDNA under the control of the CaMV 35S RNA promoter leads to the production of pelargonidin derivatives, resulting in a brick red flower phenotype. Among the transgenic petunia plants the pigmentation of the petals exhibited different expression patterns which could be categorized into the 'red', the 'variegated', and the 'white' phenotype. This system proved to be especially suitable for the investigation of gene expression by simply looking at the pigmentation pattern of the petals. The uniformity of floral pelargonidin pigmentation is inversely correlated with the number of integrated A1 copies. Furthermore, a correlation was found between the methylation status of the 35S RNA promoter and the instability of the floral pelargonidin coloration. The status of promoter methylation controlling the expression of the A1 gene seems to be influenced by the copy number and the chromosomal position of the transferred gene.

Anthocyanins↗

PubMed1989

Experimental transplantation gliomas in the adult cat brain. 3. Regional biochemistry.

Experimental brain tumours were produced in adult cats by stereotactic xenotransplantation of the rat glioma clone F98. Regional ATP, glucose and lactate were measured after 2-4 weeks on coronal cryostat sections by substrate-induced bioluminescence, potassium content was imaged by the histochemical sodium cobaltinitrite method, and regional pH by incubating cryostat sections with the fluorescent pH-indicator umbelliferone. The regional biochemical alterations were correlated with magnetic resonance imaging and tissue water content. Biochemical changes were heterogeneous in tumours but exhibited a rather uniform pattern in peritumoural oedema. ATP was consistently reduced, glucose and lactate were increased and pH was more alkaline than in normal white matter. The decrease of ATP matched the increase of water, indicating that ATP decline represents fractional dilution in the oedematous tissue rather than break-down of energy metabolism. The increased lactate levels, therefore, may originate from the tumour and not from a metabolic disturbance in the peritumoural oedematous tissue. The implications of this interpretation for the pathogenesis of peritumoural oedema are discussed.

Adenosine Triphosphate↗

PubMed1988

Functional activation of cerebral blood flow and metabolism before and after global ischemia of rat brain.

The effect of somatosensory stimulation on the local CBF (LCBF), CMRglu (LCMRglu), tissue pH, and tissue content of ATP, glucose, and lactate was studied in chloralose-anesthetized rats before and after 30 min of near-complete forebrain ischemia. In nonischemic rats LCBF in primary somatosensory cortex increased by 33%, LCMRglu increased by 55%, tissue glucose content decreased by 21%, and lactate increased by 30%. Local ATP and tissue pH did not change. Functional activation of the intact chloralose-anesthetized rat, in consequence, is associated with the stimulation of "aerobic" glycolysis but does not result in disturbances of energy or acid-base homeostasis. After 30-min ischemia and 3-h recirculation, somatosensory stimulation did not evoke any metabolic or hemodynamic alterations, although EEG and primary somatosensory evoked potentials recovered. The maintenance of normal energy state despite constant metabolic rate suggests that the postischemic generation of evoked potentials does not require measurable amounts of energy. Stimulation of glycolysis in the intact animal, therefore, may serve other purposes than fueling the energy requirements of evoked cortical activity.

Animals↗

PubMed1987

Mitochondrial respiration during recirculation after prolonged ischemia in cat brain.

Mitochondrial function was examined in cats after 1 h of complete cerebral ischemia and subsequent recirculation periods from 15 min to 56 h. During ischemia the NAD-linked respiratory control ratio and the maximal phosphorylation capacity of "free" and synaptosomal mitochondria decreased to 53% to 76% of control values. During postischemic reperfusion to 6 h, mitochondrial function was restored to 80%, remaining less than control throughout the entire investigated recirculation period with a tendency of secondary deterioration from 12 h of reperfusion onward. ADP: O ratios were unaffected during ischemia, but decreased significantly during early recirculation (15 to 30 min), and were completely restored from 45 min reperfusion onward. Correlation with electrophysiologic recordings revealed that mitochondrial dysfunction was not a limiting factor for neurophysiologic recovery during early recirculation (15 to 90 min). When the recirculation period was extended (greater than 3 h), good neurophysiologic recovery was associated with a return of mitochondrial function to control levels; inversely, poor mitochondrial function was correlated with poor neurophysiologic recovery.

Adenosine Diphosphate↗

PubMed1987

Polyamine changes in reversible cerebral ischemia.

Putrescine, spermidine, and spermine levels were measured in the cortex, caudoputamen, and hippocampus of rats during 30 min of severe forebrain ischemia (induced by occlusion of both carotid and vertebral arteries) and subsequent recirculation. During ischemia, polyamine levels did not change significantly. During postischemic recirculation, however, putrescine levels dramatically increased whereas those of spermine and spermidine did not change, with the exception of the severely damaged caudoputamen, where the concentration declined after 24 h. The increase of putrescine is explained by postischemic activation of ornithine decarboxylase and inhibition of S-adenosylmethionine decarboxylase. It is suggested that the accumulation of putrescine during postischemic recirculation may be responsible for the delayed neuronal death occurring after ischemia.

Animals↗

PubMed1987

Lactate and pH in the brain: association and dissociation in different pathophysiological states.

Brain tissue pH and lactate content were measured in rats under three different experimental conditions, namely: during complete global cerebral ischemia; after reversible near-complete cerebral ischemia; and in experimental brain tumors. At the end of the experiments brains were frozen with liquid nitrogen. A series of 20-microns thick coronal sections was prepared in a cryostat and then used for the regional determination of tissue pH (umbelliferone technique) and tissue lactate (bioluminescent technique). In addition, tissue samples were taken for the quantitative measurement of brain lactate (enzymatic fluorometric technique). The relationship between lactate content and tissue pH was different for each of the three experimental models studied: only after short-term global cerebral ischemia did an increase in the lactate content correlate with a decrease in tissue pH (r = 0.94; p less than 0.001). A highly significant increase in the lactate content (p less than 0.001) was accompanied by physiological pH values (6.96 +/- 0.08 in comparison to 6.97 +/- 0.04 in controls) during recirculation after transient cerebral ischemia and in brain tumors even by an alkaline pH shift. In view of these observations the term "lactacidosis" should not be used without measuring both the lactate content and the pH. The observed dissociation between pH and lactate is due to the fact that both parameters are regulated independently. During anaerobiosis the main source of proton production is ATP hydrolysis rather than glycolysis. It is, therefore, suggested that the terms "acidosis" and "lactosis" should be used instead of "lactacidosis."

Animals↗

PubMed1985

Superoxide dismutase activity in experimental focal cerebral ischemia.

The activity of the free radical scavenger, superoxide dismutase, was studied in focal cerebral ischemia produced in Mongolian gerbils (Meriones unguiculatus) by occluding the right common and left external carotid arteries under halothane anesthesia. After recovery from anesthesia animals were classified according to their neurologic symptoms. Five animals exhibiting neurologic symptoms such as hemiparesis and rolling seizures were reanesthetized 120 min after vascular occlusion and their brains frozen in situ with liquid nitrogen. A series of 20-micron-thick coronal sections was cut in a cryostat; pictorial representations of tissue pH, ATP, and glucose were obtained using fluorescent and bioluminescent techniques. Using a highly sensitive bioluminescent technique, Cu,Zn-superoxide dismutase (Cu,Zn-SOD) and Mn-superoxide dismutase (Mn-SOD) activities were then measured in samples from both ischemic and nonischemic regions of the remaining tissue block. Cu,Zn-SOD and Mn-SOD activities were, respectively, 13.9 +/- 0.7 X 10(3) units/g and 5.4 +/- 0.3 X 10(3) units/g in the nonischemic tissue, and 13.2 +/- 0.6 X 10(3) units/g and 5.0 +/- 0.2 X 10(3) units/g within the ischemic tissue. Thus focal cerebral ischemia does not lead to a global decrease in SOD activity, as observed by others after heart and liver ischemia.

Animals↗

PubMedDate not supplied

Bioluminescence and fluoroscopic imaging of tissue pH and metabolites in experimental brain tumors of cat.

The regional distribution of ATP, glucose, lactate and tissue pH was studied by bioluminescence and fluoroscopic imaging of intact cryostat sections of implantation tumors of cat. In tumors, marked heterogeneity of metabolites and pH was present: in solid parts ATP was similar to normal brain but glucose tended to decrease with an increase in lactate and pH to above normal; in necrobiotic regions ATP declined and pH became acidic. In peritumoral edema, ATP was consistently decreased whereas glucose, lactate and pH increased above normal. Correlation of ATP with water revealed an inverse relationship both in tumor and peritumoral edema but correlation of water with pH was direct in edema and inverse in tumors. The associations and dissociations of lactate, ATP and pH are interpreted in terms of aerobic and anaerobic glycolysis, as well as in respect to the extracellular localization of tumor edema. The findings are of relevance for the interpretation of volume selective NMR spectra and stress the importance of precise volume localization for differentiating between edema and tumor-mediated metabolic alterations.

Adenosine Triphosphate↗