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D Ebert

Publications and source records attributed to D Ebert.

102 records · Page 6Linked to original sources
PubMed1990

Sulfated N-linked oligosaccharides affect secretion but are not essential for the transport, proteolytic processing, and sorting of lysosomal enzymes in Dictyostelium discoideum.

Although previous studies have indicated that N-linked oligosaccharides on lysosomal enzymes in Dictyostelium discoideum are extensively phosphorylated and sulfated, the role of these modifications in the sorting and function of these enzymes remains to be determined. We have used radiolabel pulse-chase, subcellular fractionation, and immunofluorescence microscopy to analyze the transport, processing, secretion, and sorting of two lysosomal enzymes in a mutant, HL244, which is almost completely defective in sulfation. [3H]Mannose-labeled N-linked oligosaccharides were released from immunoprecipitated alpha-mannosidase and beta-glucosidase of HL244 by digestion with peptide: N-glycosidase. The size, Man9-10GlcNAc2, and processing of the neutral species were similar to that found in the wild type, but the anionic oligosaccharides were less charged than those from the wild-type enzymes. All of the negative charges on the oligosaccharides for HL244 were due to the presence of 1, 2, or 3 phosphodiesters and not to sulfate esters. The rate of proteolytic processing of precursor forms of alpha-mannosidase and beta-glucosidase to mature forms in HL244 was identical to wild type. The precursor polypeptides in the mutant and the wild type were membrane associated until being processed to mature forms; therefore, sulfated sugars are not essential for this association. Furthermore, the rate of transport of alpha-mannosidase and beta-glucosidase from the endoplasmic reticulum to the Golgi complex was normal in the mutant as determined by the rate at which the newly synthesized proteins became resistant to the enzyme, endo-beta-N-acetylglucosaminidase H. There was no increase in the percentage of newly synthesized mutant precursors which escaped sorting and were secreted, and the intracellularly retained lysosomal enzymes were properly localized to lysosomes as determined by fractionation of cell organelles on Percoll gradients and immunofluorescence microscopy. However, the mutant secreted lysosomally localized mature forms of the enzymes at 2-fold lower rates than wild-type cells during both growth and during starvation conditions that stimulate secretion. Furthermore, the mutant was more resistant to the effects of chloroquine treatment which results in the missorting and oversecretion of lysosomal enzymes. Together, these results suggest that sulfation of N-linked oligosaccharides is not essential for the transport, processing, or sorting of lysosomal enzymes in D. discoideum, but these modified oligosaccharides may function in the secretion of mature forms of the enzymes from lysosomes.

Acetylglucosaminidase↗
PubMed1990

Biochemical and genetic analysis of the biosynthesis, sorting, and secretion of Dictyostelium lysosomal enzymes.

Dictyostelium discoideum is a useful system to study the biosynthesis of lysosomal enzymes because of the relative ease with which it can be manipulated genetically and biochemically. Previous studies have revealed that lysosomal enzymes are synthesized in vegetatively growing amoebae as glycosylated precursor polypeptides that are phosphorylated and sulfated on their N-linked oligosaccharide side-chains upon arrival in the Golgi complex. The precursor polypeptides are membrane associated until they are proteolytically processed and deposited as soluble mature enzymes in lysosomes. In this paper we review biochemical experiments designed to determine the roles of post-translational modification, acidic pH compartments, and proteolytic processing in the transport and sorting of lysosomal enzymes. We also describe molecular genetic approaches that are being employed to study the biosynthesis of these enzymes. Mutants altered in the sorting and secretion of lysosomal enzymes are being analyzed biochemically, and we describe recent efforts to clone the genes coding for three lysosomal enzymes in order to better understand the molecular mechanisms involved in the targeting of these enzymes.

Acid Phosphatase↗
PubMed1990

[Effect of central coordination in the sense of v. Holst on the control of breathing and limb movements in humans].

We found modulations in the time-course of breathing during rhythmic abduction-adduction movements in shoulder and hip joints which can be interpreted as phenomena of central coordination in the sense of v. Holst. They occurred in more than 75% of the recorded breaths. The strength of this coordination depends on number and kind of limbs moving rhythmically and on the use of an acoustic trigger signal ("Zeitgeber") for the limb rhythm as well. Our findings indicate that reactions of the respiratory apparatus cannot be regarded only in connection with its homeostatic function and with mechanical influences. Breathing control appears integrated in the whole organism's "motor control system". Therefore, an influence of breathing movements on other motor processes is possible as well. Coordination leads to a stable temporal order between breathing and additional movements. Its possible advantage could be an energetic economization as may be concluded from analogous phenomena in coupled non-linear oscillators.

Hip Joint↗
PubMed1989

The contribution of single motor units of the biceps brachii muscle in man to the momentum in elbow flexion.

The attempt of evaluation of motor unit in vivo force in biceps brachii muscle in man shows a methodological important fact: On principle it is impossible to measure or to calculate the contribution of a single motor unit to the force output of a certain muscle. Most of the physiological data of motor units are indicated as forces measured in isolated muscles. The effect of a muscular action in joints is a momentum always. The way from muscular force to the momentum in the joint is a multidimensional and nonlinear one. Moreover some synergistic muscles act upon one joint in each case. Because we can't know their current contribution to the summarized momentum in the joint which can be measured only, it is impossible to estimate the percentage of the force of one muscle in the synergistic ensemble. It is not possible finally to calculate exactly the percentage of the single motor unit force inside one muscle, because we have motor units of different extend. An exact strategy for estimation of momenta is shown including the steps of uncertainty for calculation.

Elbow↗
PubMed1989

Coordination processes in a human motoneuronal pool.

Using two leads of a multielectrode the EMG from biceps brachii muscle in man was recorded. The test-persons were ordered to produce a sustained isometric flexion force in the elbow joint which they could control optically. In the range of about 3-5% of maximum force it was possible to identify 2-5 active motor units under this condition. Cross interval histograms were calculated showing two types of coordination between two simultaneously active motor units: 1st, periods of relative phase-coordination in different extent. This means that cross-intervals are fluctuating in a small range for short time periods. An arbitrary subdivision of the fluctuation ranges and the time periods into different classes shows that about 20-35% of the total of the cross-intervals are coordinated by relative phase dependence. In these cases the ratio of the mean discharge rates is 1:1 approximately. 2nd, another type of relationship -f the motor units active at the same time we have called "frequency coordination". This means that the fluctuations of cross-intervals around the mean discharge rate ratio are smaller than the fluctuations of the discharges of both single units around their own mean value. In these cases, which are more frequent than phase-coordination (up to 50%), the ratios of the mean discharge rates are 1:1,2 and more.

Action Potentials↗
PubMed1988

[The prognosis of carcinoid tumors of the stomach].

Follow-up examinations were carried out in 55 patients with small carcinoid tumours in the stomach (diameter 0.5-1.7 cm). For the most part, the tumours were located within the body and fundus of the stomach, with only 3 being found in the antrum. Thirty-five of the 55 patients (63.6%) had multiple gastric carcinoids, while in 46 patients (83.6%) concomitant chronic atrophic gastritis was also present. Eight patients were treated surgically, while 47 patients were merely kept under endoscopic/bioptic surveillance. In 34 out of 40 patients in whom the diagnosis had been established more than 6 months previously (longest observation period 13 years), follow-up findings were available (7 surgical patients, 27 non-operated patients). The patients submitted to surgery (average follow-up period 3.5 years) are alive and free of complaints between 1 and 9 years post-op; no metastases have occurred, but a recurrent tumour has developed in a single patient. Among the 27 non-operated patients (average follow-up period 3.6 years), 3 have died of diseases unrelated to the carcinoid tumours, in none of the other patients has there been any change in the findings. On the basis of these results it is concluded that, in carcinoid tumours of the stomach with a diameter of less than 1.0 cm, surgical treatment is not absolutely necessary, and that, in comparison with the risks represented by surgical mortality and post operative morbidity, regular endoscopic/bioptic follow-up can be considered to be adequate.

Adult↗
PubMedDate not supplied

Reduced benzodiazepine receptor binding in panic disorders measured by iomazenil SPECT.

We compared a group of nine patients with panic disorder (DSM-III-R) and depression with a matched control group of nine dysthymic patients without a previous or actual history of panic attacks or anxiety with iomazenil SPECT (single photon emission computed tomography) to evaluate panic-related abnormalities of the benzodiazepine receptor complex. The panic group had a significant decrease (p < .05, U-tests) in the regional activity index (RAI) in the following regions after 2 h: lateral inferior temporal lobes, right and left, medial inferior temporal lobes, left, inferior frontal lobes, right and left. All other regions investigated were not significantly different. The findings may be due to either regional blood flow differences or benzodiazepine receptor effects. The hypothesis that the effects are due to altered blood flow is confirmed to some extent by similar findings in the scans acquired after 10 min. Only the hypoactivity in the left lateral temporal region seemed to be independent of reduced blood flow in panic disorders.

Adult↗
PubMedDate not supplied

Positron emission tomography in female patients with borderline personality disorder.

The pathology of Borderline personality disorder (BPD) is poorly understood and its biological basis remains largely unknown. One functional brain imaging study using [(18)F]Deoxyglucose-PET previously reported frontal and prefrontal hypometabolism. We studied brain metabolism at baseline in 12 medication-free female patients with BPD without current substance abuse or depression and 12 healthy female controls by [(18)F]Deoxyglucose-PET and statistical parametric mapping. We found significant frontal and prefrontal hypermetabolism in patients with BPD relative to controls as well as significant hypometabolism in the hippocampus and cuneus. This study demonstrated limbic and prefrontal dysfunction under resting conditions in patients with BPD by FDG-PET. Dysfunction in this network of brain regions, which has been implicated in the regulation of emotion, may underlie symptoms of BPD.

Adolescent↗