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Biomedical subjects

R Schmidt

Publications and source records attributed to R Schmidt.

At least 505 records · Page 28Linked to original sources

Expression of a yeast-derived invertase in the cell wall of tobacco and Arabidopsis plants leads to accumulation of carbohydrate and inhibition of photosynthesis and strongly influences growth and phenotype of transgenic tobacco plants.

Chimeric genes consisting of the coding sequence of the yeast invertase gene suc 2 and different N-terminal portions of the potato-derived vacuolar protein proteinase inhibitor II fused to the 35S CaMV promoter and the poly-A site of the octopine synthase gene were transferred into tobacco and Arabidopsis thaliana plants using Agrobacterium based systems. Regenerated transgenic plants display a 50- to 500-fold higher invertase activity compared to non-transformed control plants. This invertase is N-glycosylated and efficiently secreted from the plant cell leading to its apoplastic location. Whereas expression of the invertase does not lead to drastic changes in transgenic Arabidopsis thaliana plants, transgenic tobacco plants show dramatic changes with respect to development and phenotype. Expression of the invertase leads to stunted growth due to reduction of internodal distances, to development of bleached and/or necrotic regions in older leaves and to suppressed root formation. In mature leaves, high levels of soluble sugars and starch accumulate. These carbohydrates do not show a diurnal turnover. The accumulation of carbohydrate is accompanied by an inhibition of photosynthesis, and in tobacco, by an increase in the rate of respiration. Measurements in bleached versus green areas of the same leaf show that the bleached section contains high levels of carbohydrates and has lower photosynthesis and higher respiration than green sections. It is concluded that expression of invertase in the cell wall interrupts export and leads to an accumulation of carbohydrates and inhibition of photosynthesis.

Amino Acid Sequence↗

Construction of an intron-containing marker gene: splicing of the intron in transgenic plants and its use in monitoring early events in Agrobacterium-mediated plant transformation.

Agrobacterium tumefaciens is a commonly used tool for transforming dicotyledonous plants. The underlying mechanism of transformation however is not very well understood. One problem complicating the analysis of this mechanism is the fact that most indicator genes are already active in Agrobacterium, thereby preventing the precise determination of timing and localisation of T-DNA transfer to plant cells. In order to overcome this obstacle a modified prokaryotic indicator gene was constructed. The expression of this indicator gene and its use in analysing early events in Agrobacterium-mediated plant transformation are described. A portable intron, derived from a plant intron, was introduced into the beta-glucuronidase (GUS) gene. In transgenic plants containing this chimaeric gene the intron is spliced efficiently, giving rise to GUS enzymatic activity. Mapping of the splice junction indicates the exact removal of the intron. No GUS activity is detected in agrobacteria containing this construct due to the lack of a eukaryotic splicing apparatus in prokaryotes. Early phases after transformation of Arabidopsis cotyledon explants were analysed using this GUS-intron chimaeric gene showing that as early as 36 h after Agrobacterium infection significant GUS activity is detected. In vivo GUS staining of transformed cells clearly shows that quickly proliferating calli expressing GUS activity are formed, mainly at the cut surface. Minor transformation events occur however throughout the whole cotyledon. These data indicate that Agrobacterium-mediated T-DNA transfer to plants is much more efficient than has been judged from experiments where selection is applied immediately. The intron-containing GUS gene can be used as an optimised marker gene in transient and stable transformation experiments.

Base Sequence↗

Use of the argon beam electrocoagulator for performing pulmonary wedge resections.

The argon beam electrocoagulator (ABC) is a new form of electrocautery that is thought to be more effective than standard electrocautery. It has been used primarily in procedures associated with major blood loss such as liver transplantation and laparotomy for trauma. It has not been used in thoracic operations. We evaluated the safety and efficacy of the argon beam electrocoagulator for performing pulmonary wedge resections in an animal model by comparing it with standard electrocautery and suture closure. Variables used to compare the three methods of resection included perioperative blood loss, duration of chest tube air leak, and depth of necrosis and severity of inflammatory reaction in the lung at ten days and 3 weeks after resection. The argon beam electrocoagulator was as effective as standard electrocautery and suture closure in controlling air leaks, and caused less acute tissue injury than standard electrocautery. The argon beam electrocoagulator provides a safe and effective method for performing small pulmonary wedge resections, and should be evaluated in the clinical setting for this purpose.

Animals↗

New findings explaining the mode of action in prevention of facial clefting and first clinical experience.

Positive clinical results of nonspecific drug prevention in 63 pregnancies at risk, in families with occurrence of cleft lip, alveolus and palate are demonstrated. The model of cleft palate in mice, induced by dexamethasone, was used for the experimental foundation of the method. A significant decrease in the cleft palate incidence, up to 70%, was shown, when the animals were given vitamin B-complex prophylactically, simultaneously and/or therapeutically. Three main possible modes of action supported by experimental results are discussed. The results may be of interest also in respect of other malformation of multifactorial origin.

Animals↗

Multiple hormone responses to stimulation with dl-fenfluramine in patients with major depression before and after antidepressive treatment.

The authors investigated 31 drug-free inpatients with major depression using dl-fenfluramine (dl-FEN) as a serotonin probe (fenfluramine stimulation test, FFT). The FFT was performed in the same individuals (intraindividual comparison) with and without application of dl-FEN and before and after antidepressive treatment. Blood samples were analyzed for prolactin, cortisol, thyrotropin (TSH), growth hormone (HGH), dl-FEN and its major metabolite dl-norfenfluramine. There was no difference in the conditions before and after treatment as regards peak plasma levels of dl-FEN. Compared with saline, significant (P less than 0.01) increases were detected for dl-FEN-stimulated cortisol and prolactin values. A significantly (P less than 0.01) lower increase in dl-FEN-stimulated prolactin values was found after treatment compared with the situation before treatment, a finding which was dependent on the type of medication which the patients were receiving at the time when the test procedure took place. Baseline and dl-FEN-stimulated cortisol values were significantly (P less than 0.001) lower and TSH values were significantly (P less than 0.01) higher in the condition after compared with the one before treatment. Patients' mean peak delta prolactin responses to dl-FEN before treatment were significantly (P less than 0.05) correlated with those of patients after subchronic treatment with fluvoxamine. Hormonal responses were neither associated with the severity of the illness nor with a specific psychopathological profile.

Adult↗

Control of developmental transcription factor sigma F by sporulation regulatory proteins SpoIIAA and SpoIIAB in Bacillus subtilis.

The sporulation operon spoIIA of Bacillus subtilis consists of three cistrons called spoIIAA, spoIIAB, and spoIIAC. Little is known about the function of spoIIAA and spoIIAB, but spoIIAC encodes a sigma factor called sigma F, which is capable of directing the transcription in vitro of genes that are expressed in the forespore chamber of the developing sporangium. We now report that the products of the spoIIA operon constitute a regulatory system in which SpoIIAA is an antagonist of SpoIIAB (or otherwise counteracts the effect of SpoIIAB) and SpoIIAB is, in turn, an antagonist of SpoIIAC (sigma F). This conclusion is based on the observations that (i) overexpression of spoIIAB inhibits sigma F-directed gene expression, (ii) a mutation in spoIIAB stimulates sigma F-directed gene expression, (iii) a mutation in spoIIAA blocks sigma F-directed gene expression, and (iv) a mutation in spoIIAB relieves the block in sigma F-directed gene expression caused by a mutation in spoIIAA. The SpoIIAA/SpoIIAB/SpoIIAC regulatory system could play a role in controlling the timing of sigma F-directed gene expression and/or could be responsible for restricting sigma F-directed gene expression to the forespore chamber of the sporangium.

Bacillus subtilis↗

Toxicokinetics of tumor promoters of mouse skin. I. Metabolism of phorbol and ingenol esters by mouse liver microsomes.

The metabolism of ten selected phorbol esters and of one ingenol ester was investigated in mouse liver microsomes fortified with cofactors. The major metabolites were generated by an esterolytic activity in the microsomes. The following 12,13-diesters were cleaved readily to yield the 13-monoesters: 12-O-tetradecanoylphorbol-13-acetate, phorbol-12,13-dipropionate, bis(13-O-acetylphorbol)-12, 12'-tetradecanedioate, phorbol-12,13-dibenzoate; the monoesters 12-O-tetradecanoylphorbol and 3-O-tetradecanoylingenol yielded the corresponding parent alcohols. Other 12,13-di- or 13-monoesters such as 'inverse TPA', i.e. 12-O-acetylphorbol-13-tetradecanoate, phorbol-12,13-didecanoate, 12-O-retinoylphorbol-13-acetate, phorbol-13-decanoate and 12-O-tetradecanoyl-4 alpha-phorbol-13-acetate were either comparatively or completely resistant to esterolysis. The data indicate that metabolism of diterpene esters depends on the nature and position of the acyl moiety, as well as on the structure of the diterpene moiety. The esterolytic activity in mouse liver microsomes can be inhibited by i.p. administration of bis(4-nitrophenyl)phosphate to mice. Evidence for other relevant metabolic pathways besides esterolysis was lacking.

Animals↗

Long-term experience of a trial in multi-infarct dementia.

A report is given on the natural history of multi-infarct dementia (MID) in 94 patients over a period of 5 years and describes neuroimaging criteria that may be used in order to more reliably separate vascular (VD) from primary degenerative types of dementia (DTD). The annual mortality rate of MID patients was 13%. Age and nocturnal confusion were found to be the most efficient predictors for fatal prognosis. Psychosocial adjustment, in contrast, indicated better outcome. In respect to differential diagnosis MRI revealed infarcts, basal ganglia lacunes and confluent white matter lesions as the most effective discriminators between VD and DTD. The typical patchy pattern found in almost half of the patients with VD, and significant differences in 5-7 Hz range as shown by EEG mapping can also be used for increasing the accuracy of the clinical diagnosis.

Aging↗

Reconstructed skin from cultured human keratinocytes and fibroblasts on a collagen-glycosaminoglycan biopolymer substrate.

A lattice prepared from biopolymer substrate bovine skin collagen and chondroitin-6-sulfate (glycosaminoglycan) served as a support for normal human keratinocytes and fibroblasts. Air exposure of the lattice on an agarose block gave rise to reconstructed epidermis, the histological features of which are very similar to normal human epidermis. Indirect immunofluorescence staining of the plasma membrane-associated transglutaminase, the enzyme responsible for the synthesis of the cornified envelope, revealed the same tissue distribution as observed in vivo. Cell cycle analysis showed a large shift of the normal human keratinocyte population into S-phase and cell division during the 1st week postinoculation. Furthermore, the effects of two modulators of differentiation (25-hydroxycholesterol and sodium butyrate) on the reconstruction of the epidermis were evaluated.

Animals↗

Friedreich's ataxia in 13 children: presentation and evolution with neurophysiologic, electrocardiographic, and echocardiographic features.

Thirteen children with Friedreich's ataxia were reviewed. The clinical presentation and evolution of the disease was compared to that observed in large series--based mainly on adult patients--and the few studies in children. The mean age of onset (5.3 +/- 2.7 years) was lower than that reported in the former studies. Progressive unremitting ataxia of all four limbs was the earliest and most consistent finding, whereas dysarthria and loss of joint or vibration sense occurred with less frequency than that reported in adult series. The tendon jerks were absent or reduced in the lower limbs in almost all children. The universal absence of lower limb reflexes was shown to be too rigid to be obligatory for the diagnosis of early cases of Friedreich's ataxia. Electrophysiologic investigations revealed typical findings, ie, normal or low-normal motor conduction velocities and absent sensory responses. Electromyography showed more features of denervation in the lower limbs than in the upper limbs. Cardiac symptoms and signs were minimal, whereas electrocardiographic abnormalities occurred in 92% of patients, presenting mostly as significant T-wave changes. Concentric symmetric thickening of both the interventricular and left ventricular posterior walls was the major echocardiographic finding.

Adolescent↗

[Distribution pattern of chemical in surface waters as a reflexion of entry pattern--nonvolatile halogenated hydrocarbons].

The concentrations of some nonvolatile halogenated hydrocarbons in surface waters of an industrialized city and its surroundings are given. About 80% of the ballast isomers of hexachlorocyclohexane (alpha, beta and delta BHC) and of DDT and its metabolites are in the range of less than 5 micrograms l-1, whereas ca. 50% of lindane (gamma BHC) were found to be between 5 and 100 micrograms l-1. Starting form the remarks about the differential-diagnostic assessment of environmental concentrations conclusions as to the origin of hexachlorocyclohexane isomers are drawn with the help of their distribution pattern. A high part of the gamma isomer, compared with the ballast isomers means an application (e.g. against mosquitos). This fact may be supported if it coincides with the months typical for such an application. in contrast to this if you have high percentages of alpha, beta and delta hexachlorocyclohexane, it indicates a point source or diffuse inputs of technical BHC. If all four isomers are present on a comparable and very low level this may reflect a remobilization from the sediment.

DDT↗

[Reduction of reactivity to allergic rhinitis with intravenous administration of calcium. Clinical-experimental study on the effect of changes of local airway resistance after nasal allergen provocation].

The antiallergic activity of calcium was investigated in 25 patients with allergic rhinitis by nasal provocation with increasing doses of phleum pratense during a symptom free interval. Prior to that provocation, the patients received 9 mmol calcium (Calcium-Sandoz) i.v. or placebo respectively (double blind cross-over design). The concentration of serum calcium increased after calcium injection by 0.45 +/- 0.055 mmol/l. Calcium exerted a significant protective effect as compared to placebo: higher allergen doses, (p = 0.021) i.e. 20433 biological units/ml vs. 7494 biological units/ml, were required in order to induce a defined allergic reaction (50% decrease of nasal air flow). The data thus furnish evidence that intravenous calcium reduces the allergic response in type I allergy.

Adult↗

[Ergotism: an occasional unrecognized cause of acute ischemia of the extremities].

Vasospasm related to ergot intoxication has been recognised since the Middle Ages when it occurred due to ingestion of rye contaminated with Claviceps purpurea. Today ergotism is a rare cause of peripheral ischaemia, most often associated with ergotamine tartrate therapy for migraine headaches. Recognition of the typical angiographic pattern is important, as the classic drug history may not be obtained, and the cause of the ischaemia can be overlooked. Early diagnosis is important as the outcome may be serious if left untreated. Arterial vasospasm, collateralisation, and secondary thrombus formation are the major angiographic findings. Ergotism responds to conservative therapy which includes drug withdrawal, intravenous nitroprusside, fluid therapy and heparinisation. We describe the angiographic findings of four cases and report on the results of therapy.

Adult↗

[Effect of alloxans on pancreatic B-cells with special regard to the alloxan-metal-complex theory. I. Effects of alloxan, alloxan-zinc chelates, dilauric acid and colchicine on blood sugar and rate of mitosis of B-cell Langerhans islets].

Alloxan, alloxan-zinc-chelate, sodium salt of dialuric acid, and colchicine significantly raised the blood sugar level under the previously mentioned experimental conditions 28 h after the application. The typical three-phase blood sugar curve development after alloxan (initial hyperglycemia, hypoglycemia, permanent hyperglycemia) was only approximately reached by dialuric acid which initiated, however, instead of the initial hyperglycemia a more pronounced hypoglycemic phase within the first 6 h. Alloxan-zinc-chelate protractedly and significantly made the blood sugar's increase up to the 7th d post injectionem, without being able to maintain a permanent hyperglycemia with half-normal dosage in comparison with alloxan. Non-diabetogenic alloxan doses (19 mg/kg i. v.) and the appropriate alloxan-zinc-chelate dosage (35 mg/kg) led to a significant increase of the blood sugar only in the chelate group with the long-term test up to 10 d, suggesting an increased and prolonged effect of the metal-chelates by stabilization of alloxan. The tested substances differently acted on the mitotic frequency of B-cells. The mitosis did not increase in the alloxan-zinc- and dialuric acid treated animals and was similar to normal animals far below the fractions of 1/10(6). A 4- and 5-fold increase of the mitotic frequency in the colchicine or alloxan treated animals as well as an accumulation of delayed metaphases suggest an impeded transition to the anaphase and include alloxan among the mitotic poisons.

Alloxan↗