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Biomedical subjects

H Heller

Publications and source records attributed to H Heller.

At least 19 recordsLinked to original sources

Luetic cervical adenitis in patients with human immunodeficiency virus type 1 infection.

The clinical course of syphilis may be altered in some patients with human immunodeficiency virus type 1 infection. We report two cases of syphilis in patients with human immunodeficiency virus type 1 infection who presented with marked unilateral anterior cervical adenopathy after engaging in oral-genital sex. Neither of the patients had evidence of oropharyngeal chancres. One patient developed a cutaneous rash of secondary syphilis soon after the cervical adenopathy developed. Both patients responded well to antibiotic therapy.

Adult

Brain dysfunction during motor activation and corpus callosum alterations in schizophrenia measured by cerebral blood flow and magnetic resonance imaging.

Sixteen unmedicated (14 never-medicated, 2 with washout periods of 1-2 weeks) schizophrenic patients displaying positive symptoms (e.g., formal thought disorder, hallucinations, delusions) without negative symptoms (e.g., flattening of affect, loss of energy, anhedonia--type I patients), 15 unmedicated (with washout periods from 1 week to 2 years) patients with marked negative symptomatology [type II patients; criterion score below 15/above 35 on the Munich version of the Scale of Assessment of Negative Symptoms (SANS), respectively], and 31 matched normal controls were investigated using regional cerebral blood flow [rCBF; dynamic single-photon emission computerized tomography (SPECT) with Xenon-133 as tracer] and magnetic resonance imaging (MRI; spin-echo technique, T1 weighted, midsagittal cuts). rCBF measurements were performed during both resting conditions and simple motor activation. Separately, on the same day, we performed a planimetric evaluation of the callosal-brain ratio in all subjects using MRI. In accordance with previous results on a smaller sample, we found signs of diffuse bilateral rCBF hyperactivation in type I patients, as compared with signs of nonreactivity in type II schizophrenics. Both activation patterns were different from a strictly contralateral sensorimotor rCBF activation seen in normal persons (only 8 studied with SPECT). The planimetry of relative callosal area did not reveal differences compared to normal persons, when type I/II patients were taken together. However, the threefold increased variance as compared with that found in normal persons suggested biological heterogeneity in patients. We found an increase of relative callosal size in type I as compared with type II patients. In the light of some recent findings linking lack of laterality of several brain functions to increased callosal size, we propose lack of laterality/diffuse hyperactivation and increased callosal size to be connected with positive symptomatology/good prognosis schizophrenia, and vice versa.

Activities of Daily Living

A ubiquitin-protein ligase specific for type III protein substrates.

A previously studied species of ubiquitin-protein ligase contains specific sites for the binding of basic (Type I) and bulky hydrophobic (Type II) NH2-terminal amino acid residues of protein substrates. We now describe another enzyme that ligates ubiquitin specifically to proteins that have NH2-terminal residues other than the above two categories (Type III substrates). The new species of ligase, that we call E3 beta, is separable from the formerly described ligase (termed E3 alpha) by affinity chromatography on protein substrate columns. E3 beta was partially purified from extracts of rabbit reticulocytes and was shown to be required for the breakdown of Type III proteins. Apart from its different substrate specificity, it resembles E3 alpha in some physical properties, in a requirement for ubiquitin carrier protein (E2) for conjugate formation, and in its action to ligate multiple ubiquitin units to the substrate protein. The denatured derivative of bovine pancreatic ribonuclease is a specific substrate for E3 alpha, while that of ribonuclease S-protein is a good substrate for E3 beta. Since S-protein is formed by the removal from ribonuclease of NH2-terminal S-peptide, it is suggested that E3 beta interacts with an NH2-terminal determinant exposed in ribonuclease S-protein.

Animals

Assessment of stratified inhomogeneity within distal alveolar space with respect to oxygen uptake.

Investigations were made as to whether or not there is a limitation of oxygen transport by stratified inhomogeneity in distal alveolar gas. Experiments were performed on 2 subjects. Single breath manoeuvres were carried out with similar phases of inspiration and expiration but varying breath-hold times. The inspiratory gas contained a small amount of oxygen labeled carbon dioxide, C18O2. End-expiratory gas was analysed on its residual C18O2 partial pressure by mass spectrometry. For evaluating a stratificational conductance, compartment model analysis was applied on the breath-hold data. Stratificational conductance has been found to be higher than 553 ml.mmHg-1. min-1. When transferred to oxygen transport, this means that stratificational conductance is more than 10 times higher than oxygen diffusing capacity. It can be concluded that (i) stratified inhomogeneity in distal alveolar space does not exhibit a limiting factor of oxygen uptake in lungs, (ii) a contribution of stratificational effects to sloping alveolar plateau is expected to be of minor importance.

Adult

Oral physostigmine treatment for patients with presenile and senile dementia of the Alzheimer's type: a double-blind placebo-controlled trial.

Twelve patients aged 53 to 89 years with presenile or senile dementia of the Alzheimer's type participated in a treatment trial of oral physostigmine. Patients first received the drug during an open dose-finding phase. In a double-blind crossover design phase, the patients' memory performance during treatment with an optimal memory-enhancing dose was compared with memory performance during placebo treatment. Response to medication was assessed by the Delayed Recognition Span Test, the Selective Reminding Test, and the Alzheimer's Disease Assessment Scale. Intergroup differences in response to physostigmine were nonsignificant. Age at onset of the disease did not differentiate partial responders from nonresponders.

Administration, Oral

Binding sites of ubiquitin-protein ligase. Binding of ubiquitin-protein conjugates and of ubiquitin-carrier protein.

It was found previously that the enzyme ubiquitin-protein ligase (E3) contains specific protein substrate binding sites that are responsible for the selection of proteins for degradation by the ubiquitin system. In the present study, we have tried to gain more insight into the mode of action of E3 by the characterization of other binding sites of this enzyme. Following the ligation of ubiquitin to 125I-lysozyme, the conjugates produced are very tightly bound to E3, as indicated by size analysis on glycerol density gradient centrifugation. The strong binding of ubiquitin-protein conjugates to the enzyme may account for the apparently processive addition of multiple molecules of ubiquitin to the protein substrate. Both the protein substrate moiety and the ubiquitin moiety participate in the interaction of ubiquitin-protein conjugates with E3, as indicated by competition with specific agents and by the comparison of the binding of ubiquitin-conjugated protein to that of free protein. In addition to the binding of its substrates and products, E3 also appears to interact with some of the enzymes with which it acts in concert. When E3 is incubated with the ubiquitin-carrier protein E2, a complex is formed between the two enzymes as analyzed on glycerol gradients. The formation of an E2.E3 complex may facilitate the transfer of activated ubiquitin from E2 to the protein substrate bound to the ligase.

Adenosine Triphosphate

Maze-learning behavior in early adrenalectomized rats.

Rats adrenalectomized (ADX) on day 11 of life display enhanced brain growth due, at least in part, to a stimulation of cell proliferation and myelinogenesis. The present study investigated some functional consequences of this treatment. Rats were ADX or sham-operated (SHAM) on postnatal day 11 and then tested in adulthood for their problem-solving ability in a Hebb-Williams maze. The mean number of errors committed by ADX rats was lower than that of the SHAM controls on every test problem of the maze. ADX subjects also left the start box more quickly and ran the maze faster than the controls. When a subset of these same subjects was tested for running wheel activity, the ADX animals showed greater baseline running behavior and also learned more readily to respond to a fixed-interval schedule of reinforcement. The remaining animals were subjected to carcass analysis, which revealed that ADX rats under the food-restricted conditions necessary for maze testing had a lower percentage of body fat and a higher relative water content than SHAMs. Although there may be some relationship between enhanced maze-learning performance and altered activity or motivation in the ADX animals, the overall results suggest that the performance of these subjects reflects a real difference in learning ability. The neural mechanisms underlying this difference remain to be elucidated.

Adrenal Glands

[Changes in the sensitivity of the cornea in patients with intracerebral tumors. Studies of patients with meningioma of the cranial base and neurinoma of the trigeminal nerve and the vestibulocochlear nerve using the Draeger esthesiometer].

The center of the cornea was measured preoperatively in 29 patients suffering from intracranial tumors (acoustic neuroma, trigeminus neuroma, basal meningioma). These measurements were made with the Draeger electronic-optical esthesiometer; the results were supplemented by an analysis of tumor diameters determined by computer tomography. In each case one-half of the patients with acoustic neuromas and medial meningiomas of the wing of the sphenoid bone manifested a reduction in sensitivity at the center of the ipsilateral cornea (normal: 0.8 to 1.7 x 10(-5) N). The diameters of the sensitivity-reducing acoustic neuromas ranged from 15 mm to 45 mm. It may be deduced both from the topographic conditions at the skull base in the vicinity of the porus acusticus internus and from the conditions associated with a pressure-induced lesion of a peripheral nerve that medial acoustic neuromas as small as 10.1 mm in diameter can lead to a reduction in the conductivity of the ipsilateral trigeminal nerve. Only when they attain a diameter of 28.4 mm and when the proportions of the skull base are equally spacious do the acoustic neuromas regularly cause an ipsilateral corneal hypesthesia.

Adult

[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