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Biomedical subjects

H Heller

Publications and source records attributed to H Heller.

At least 73 records · Page 4Linked to original sources

[Comparative studies of cerebral blood flow measurements and measurements of the size of the corpus callosum in patients with schizophrenia].

In this study healthy subjects and schizophrenic patients of the so-called Type I and Type II subgroups were examined in each case with a morphological method to determine the size of the corpus callosum and with a method to measure a physiological functional parameter, namely, the regional cerebral blood flow (rCBF). MR and dynamic single photon emission CT were used (in our case as differential method). The study reveals for the first time classified into subgroups of the disease, scientifically measured differences both in the size of the corpus callosum and in the distribution pattern of the blood flow. Whereas the patients of type I had an enlarged corpus callosum and increased blood flow during the task with which they were confronted, these organs were mainly smaller in size with type II patients without an increase in the global blood flow during the relevant task. The statistical data--averaged over patient groups--show these differences clearly, but due to biological scatter it has so far not been possible to arrive at a diagnosis in individual cases.

Adult↗

Alterations in components of the ubiquitin-protein ligase system following maturation of reticulocytes to erythrocytes.

Previous studies have shown that the activity of the ubiquitin-mediated proteolytic system declines markedly following reticulocyte maturation, but the specific alterations responsible for this phenomenon have not been defined. We find that the rate of ATP-dependent degradation of 125I-albumin is reduced 20-fold in lysates of rabbit erythrocytes, as compared to reticulocyte lysates. The activity of the proteolytic system in erythrocyte extracts can be restored by supplementation with components of the ubiquitin-protein ligase system purified from reticulocytes by affinity chromatography. These components are the ubiquitin-carrier protein E2, the activity of which is nearly completely absent, and the ligase E3, the activity of which is partially reduced in erythrocytes. Erythrocyte extracts contain other ligases which attach a single, or a few ubiquitin molecules to proteins; these products are different from the multi-ubiquitin derivatives which are formed by the ligase system of protein breakdown. Mature red cells may thus serve to distinguish between different ubiquitin-protein ligase systems with presumably different functions.

Adenosine Triphosphate↗

[Magnetic resonance tomography of the postoperative lumbar spine. A comparison of the MR versus CT images in recurrent intervertebral disk prolapse].

In the present study, 40 patients who had undergone disc surgery were examined by high resolution CT and MR for possible recurrence of the disc prolapse and the results are compared. It appears that high resolution spinal MR, using its various tissue parameters provides no new insights into possible recurrence of a disc prolapse. As is the case with CT, the investigator must also evaluate other morphological and clinical factors. In spite of this, MR can be useful in the investigation of abnormal spines.

Diagnostic Errors↗

The protein substrate binding site of the ubiquitin-protein ligase system.

In order to gain insight into the mechanisms that determine the selectivity of the ubiquitin proteolytic pathway, the protein substrate binding site of the ubiquitin-protein ligase system was identified and examined. Previous studies had shown that the ligase system consists of three components: a ubiquitin-activating enzyme (E1), ubiquitin-carrier protein (E2), and a third enzyme, E3, the mode of action of which has not been defined. E3 from rabbit reticulocytes was further purified by a combination of affinity chromatography, hydrophobic chromatography, and gel filtration procedures. A 180-kDa protein was identified as the subunit of E3. Two independent methods indicate that E3 has the protein binding site of the ubiquitin ligase system. These are the chemical cross-linking of 125I-labeled proteins to the E3 subunit and the functional conversion of enzyme-bound labeled proteins to ubiquitin conjugates in pulse-chase experiments. The trapping of E3-bound protein for labeled product formation was allowed by the slow dissociation of E3 X protein complex. The specificity of binding of different proteins to E3, examined by both methods, showed a direct correlation with their susceptibility to degradation by the ubiquitin system. Proteins with free alpha-NH2 groups, which are good substrates, bind better to E3 than corresponding proteins with blocked NH2 termini, which are not substrates. Oxidation of methionine residues to sulfoxide derivatives greatly increases the susceptibility of some proteins to ligation with ubiquitin, with a corresponding increase in their binding to E3. However, a protein derivative which was subjected to both amino group modification and oxidation binds strongly to the enzyme, even though it cannot be ligated to ubiquitin. It thus seems that the substrate binding site of E3 participates in determining the specificity of proteins that enter the ubiquitin pathway of protein degradation.

Animals↗

Disk processes in MR.

Disk processes can be differentiated in MR with the introduction of high resolution coils and the use of a multi slice technique with a minimal slice thickness of 5 mm. By using a sensitive double echo sequence we found that in the 80 patients examined the size and extent of the posterior herniation could be well demonstrated. Sagittal slices show the relationship of the herniation to the spinal cord. The pathomechanical parts of a disk process such as ruptured or preserved anulus fibrosus, perforated or intact posterior longitudinal ligament can be differentiated. For lateral lying processes in connection with the foramen intervertebral and the spinal roots an axial slice parallel to the intervertebral space is recommended. All CT findings especially in the cervical spine region were shown and further qualified.

Cervical Vertebrae↗

Combination therapy with lecithin and ergoloid mesylates for Alzheimer's disease.

A 10-week placebo-controlled double-blind crossover protocol of combination therapy with lecithin and ergoloid mesylates was conducted in seven patients with presenile and senile dementia, Alzheimer's type. The patients' abilities to detect spatial arrangements, to recognize faces, and to identify new words on the Delayed Recognition Span Test were not significantly improved. Dementia Rating Scale scores before treatment were not significantly different from those after treatment.

Aged↗

Occurrence of a polyubiquitin structure in ubiquitin-protein conjugates.

In the ubiquitin-mediated pathway for the degradation of intracellular proteins, several molecules of ubiquitin are linked to the protein substrate by amide linkages. It was noted that the number of ubiquitin-protein conjugates and their apparent molecular size are higher than expected from the number of amino groups in the protein. When the amino groups of ubiquitin were blocked by reductive methylation, it was efficiently conjugated to lysozyme, but the higher-molecular-weight conjugates were not formed. This suggests that the higher-molecular-weight conjugates with native ubiquitin contain structures in which one molecule of ubiquitin is linked to an amino group of another molecule of ubiquitin. Methylated ubiquitin stimulated protein breakdown at about one half the rate obtained with native ubiquitin, and isolated conjugates of 125I-lysozyme with methylated ubiquitin were broken down by reticulocyte extracts. These findings indicate that the formation of polyubiquitin chains is not obligatory for protein breakdown, though it may accelerate the rate of this process.

Animals↗

[Diagnosis of bone necrosis by magnetic resonance tomography. The potentials for early diagnosis].

Twenty-eight patients with necrosis in the hip joint, the femoral condyles and the talus were examined by MR tomography. This revealed various features whose frequency depended upon the various stages of the necrosis. Three patients who showed no, or only indefinite, changes on radiographs, displayed clear evidence of necrosis on MR. Staging of femoral head necrosis on the basis of MR criteria is suggested, as well as a suitable procedure for early diagnosis. Accurate localisation and knowledge of the extent of the necrosis by means of MR makes it possible to plan an osteotomy accurately.

Adolescent↗

[Nuclear magnetic resonance tomography of the spine].

The present paper deals with the results of 48 MR examinations of known spinal abnormalities. The use of a method strictly related to the individual problem helps to reduce the duration of the examination. Sagittal cuts are particularly useful for demonstrating much of the spinal canal. The spin-echo method is used for all examinations. Demonstration of the cord was performed by using short repetition and echo times (TR, TE). For showing the outer margin of the spinal canal, longer TR and TE should be selected. Surface coils are important for demonstrating spinal disease, since the larger images can be performed without increasing the duration of the examination.

Humans↗

[MR imaging of the cervical spine using special coils].

The signal/noise ratio of MR images can be improved for organs near the surface by means of special coils. It is shown for neck imaging that a close-fitting saddle-shaped coil is more suitable for application between C 2 and Th 1, than a saddle coil for the entire head or a disc-shaped coil. Such a close-fitting saddle-shaped coil is an essential prerequisite for effective neuroradiological diagnoses of the spinal cord with nerve roots, of the spinal column, and of the vessels of the neck.

Cervical Vertebrae↗

Role of the alpha-amino group of protein in ubiquitin-mediated protein breakdown.

Previous studies suggest that the conjugation of ubiquitin to NH2 groups of proteins is required for protein breakdown. We now show that the selective modification of NH2-terminal alpha-NH2 groups of globin and lysozyme prevents their degradation by the ubiquitin proteolytic system from reticulocytes. The conjugation by ubiquitin of epsilon-NH2 groups of lysine residues, usually seen in multiples, was also inhibited in alpha-NH2-blocked proteins. Naturally occurring N alpha-acetylated proteins are not degraded by the ubiquitin system at a significant rate, while their nonacetylated counterparts from other species are good substrates. This suggests that one function of N alpha-acetylation of cellular proteins is to prevent their degradation by the ubiquitin system. alpha-NH2-blocked proteins can have their activity as substrates for degradation increased by incorporation of alpha-NH2 groups through the introduction of polyalanine side chains. Proteins in which most epsilon-NH2 groups are blocked but the alpha-NH2 group is free are degraded by the ubiquitin system, but at a reduced rate. It is therefore suggested that the exposure of a free NH2 terminus of proteins is required for degradation and probably initiates the formation of ubiquitin conjugates committed for degradation.

Acetylation↗

ATP-dependent degradation of ubiquitin-protein conjugates.

Previous studies have indicated that the ATP-requiring conjugation of ubiquitin with proteins plays a role in the energy-dependent degradation of intracellular proteins. To examine whether such conjugates are indeed intermediates in protein breakdown, conjugates of 125I-labeled lysozyme with ubiquitin were isolated and incubated with a fraction of reticulocyte extract that lacks the enzymes that carry out ubiquitin-protein conjugation. ATP markedly stimulated degradation of the lysozyme moiety of ubiquitin conjugates to products soluble in trichloroacetic acid. By contrast, free 125I-labeled lysozyme was not degraded under these conditions, unless ubiquitin and the three enzymes required for ubiquitin conjugation were supplemented. Mg2+ was absolutely required for conjugate breakdown. Of various nucleotides, only CTP replaced ATP. Nonhydrolyzable analogs of ATP were not effective. In the absence of ATP, free lysozyme is released from ubiquitin-lysozyme conjugates by isopeptidases present in the extract. Thus, ATP is involved in both the formation and the breakdown of ubiquitin-protein conjugates.

Adenosine Triphosphate↗

[Concentrations and levels of activity of important serum protein components in preserved serum].

The content of transport proteins, immune globulins, components of the complement system and protease inhibitors were estimated in two different plasma preparations, using bioassays by chromogenic substrates and laser nephelometry. The content of proteins under consideration was found about 50% less than in untreated human plasma. Some proteins such as antithrombin III and factor XIII are missing. The results are discussed in respect to clinical used of plasma preparations.

Antithrombin III↗