Showing papers by "University of Düsseldorf published in 1984"

Autoimmune human T lymphocytes specific for acetylcholine receptor

Abstract: Myasthenia gravis is one of the best characterized human autoimmune disorders1–4. Circulating autoantibodies to the nicotinic acetylcholine receptor (AChR) at the neuromuscular junction play a prominent part in the effector phase of the disease5,6, but little is known about the induction phase, that is, the immunoregulation. Indirect evidence, such as thymic abnormalities7 and the association with certain histocompatibility antigens (for example HLA-B8,-DR38,9) suggests a defect of immunoregulation at the level of thymus-dependent (T) lymphocytes. We report here on the isolation of autoreactive T cells from six patients with myasthenia gravis. From one of these patients, who is homozygous for HLA-DR3, we established a long-term T-cell line. The line cells are specific for purified fish and human AChR, display the surface phenotype of inducer/helper T cells and are genetically restricted to HLA-DR3. AChR-induced proliferation could be inhibited with two monoclonal antibodies against monomorphic DR determinants and also with DR3-specific alloantiserum.

Hyperinsulinaemia in non-cirrhotic haemochromatosis: impaired hepatic insulin degradation?

Abstract: This study investigated early alterations of glucose metabolism in idiopathic haemochromatosis. Circulating concentrations of glucose, insulin, C-peptide, glucagon, and gastric inhibitory polypeptide (GIF) were measured after a 100-g oral glucose load in 10 men with idiopathic haemochromatosis in the non-cirrhotic stage of the disease. All had normal glucose tolerance and normal body weight. Ten matched healthy subjects were studied as controls. Insulin concentrations increased to significantly higher levels in patients with idiopathic haemochromatosis than in the control subjects from 30 to 180min after the glucose load (p 0.05). Concentrations of glucose, glucagon, C-peptide, and GIF were not significantly different at any time (p> 0.05). Thus, patients with idiopathic haemochromatosis show hyperinsulinaemia and hence insulin resistance without impaired glucose tolerance in the non-cirrhotic stage. Since pancreatic insulin secretion (C-peptide), glucagon secretion, and the entero-insulinar axis (GIP) are not impaired in these non-cirrhotic patients with idiopathic haemochromatosis, iron accumulation in the hepatocytes may be responsible for the impaired insulin effect and may cause impaired hepatic insulin extraction.

The inheritance of common baldness: Two B or not two B ?

Abstract: So far, it is a widely accepted opinion that androgenetic alopecia is caused by an autosomal dominant gene with reduced penetrance in women. This view is essentially based on a family study performed by Osborn in 1916. She believed that balding men would be either heterozygous (Bb) or homozygous (BB), whereas balding women would be homozygous (BB). By contrast, we here present five arguments favoring a polygenic inheritance of the trait: (1) the high prevalence of the trait, (2) the distribution of balding patterns in the general population along a gaussian curve of variation, (3) the fact that the risk increases with the number of relatives already affected, (4) the slightly increased risk of relatives of severely affected women as compared to the relatives of mildly affected women, and (5) the fact that a predisposition inherited from an affected mother is of greater importance than that inherited from an affected father. In conclusion, the simple mendelian model of Bb and BB can no longer be upheld.

The diencephalon in schizophrenia: evidence for reduced thickness of the periventricular grey matter.

Abstract: To find out whether ventricular enlargement in schizophrenia, as demonstrated by neuroradiological methods, is caused by an atrophy of ventricle surrounding diencephalic structures, volume measurements and linear measurements of the whole thalamus, all large thalamic subnuclei and some extrathalamic brain parts were carried out on serial sections of post mortem brains belonging to the Vogt collection. The only significantly diminished parameter of this study was the thickness of the periventricular grey matter surrounding the third ventricle, while the volume and linear measurements of the whole thalamus and all large thalamic subnuclei were not significantly changed. The findings are discussed with respect to current hypotheses of diencephalic dysfunction in schizophrenia.

Structural changes in axillary eccrine glands following long-term treatment with aluminium chloride hexahydrate solution.

Abstract: Axillary skin biopsies from fifteen patients with axillary hyperhidrosis who had received long-term treatment with aqueous aluminium chloride solution were examined histologically. The apocrine glands were normal, but the eccrine glands showed conspicuous morphological changes of varying severity. These included vacuolization of the secretory epithelium, dilatation of eccrine acini with atrophy of secretory cells, and accumulation of PAS-positive, diastase-resistant material in the dilated lumen of the secretory coils. The histological changes correlated in most patients with decreased secretion of sweat. We conclude that long-term blockage of the distal acrosyringium due to aluminium salts may lead to functional and structural degeneration of the eccrine acini.

Biosynthesis and regulation of the peroxisomal methanol oxidase from the methylotrophic yeast Hansenula polymorpha.

Abstract: The biosynthesis of methanol oxidase, a peroxisomal enzyme in the methanol-utilizing yeast Hansenula polymorpha, was studied in vitro. Translation of Hansenula mRNA in a rabbit reticulocyte lysate yields methanol oxidase protein in high amounts. The apparent molecular mass of the protein was found to be identical to the subunit of the functional multimeric enzyme, which indicates the absence of an N-terminal extension typical of most transported proteins. The regulation of methanol oxidase by glucose repression and derepression as well as by induction of methanol was shown to be controlled at the level of transcription. Two mutants of Hansenula polymorpha unable to grow on methanol as a carbon and energy source were shown to be affected in methanol oxidase synthesis.

Detection of early atherosclerotic lesions by duplex scanning of the carotid artery.

Abstract: A high-resolution ultrasound B-mode imaging system combined with a 16-sequential range-gated pulsed Doppler flow measuring device was used for the evaluation of nonstenotic extracranial carotid artery disease Various types of atherosclerotic lesions were differentiated by Duplex system examinations in 54 carotid arteries examined in vitro in a postmortem study and in 51 carotid arteries examined in vivo from patients with angiographically proven cerebrovascular disease In addition, the multigated Doppler system allowed the analysis of flow velocity profiles throughout the carotid arteries, the distinction between intraarterial flow and recent thrombus, and in particular the estimation of local flow alterations, which are diagnostic in the presence of sonolucent and shadowed plaques behind echo-dense lesions A number of difficulties, which at present limit the application of Duplex system examination as a non-invasive "stand alone" method for detecting carotid disease, are discussed

Effect of propafenone in the wolff-parkinson-white syndrome: Electrophysiologic findings and long-term follow-up

Abstract: The electrophysiologic and long-term efficacy of propafenone, a relatively new antiarrhythmic agent, was assessed in 47 patients with accessory pathways. In 23 patients (group I), the electrophysiologic effects were assessed initially. In 19 patients in this group and in 24 additional patients (group II), long-term therapy with oral propafenone was initiated. The mean age of the patients was 38 years in group I and 41 years in group II. The duration of a history of tachycardia in both groups was 12 years (mean); 14 patients previously had had attacks of syncope. During the electrophysiologic study in group I, propafenone did not change the spontaneous sinus rate. Corrected sinus node recovery time as well as the AH interval, HV time, QRS duration and effective refractory periods of the atria and ventricles was significantly prolonged. The effective refractory period of the accessory pathway increased from 238 to 322 ms (p

Myofibroblast-like cells in human anterior capsular cataract

Abstract: In six cases of anterior capsular cataract, cells present in the subcapsular zone were investigated. In addition to orga nelles previously described, the cells were found to contain 7 nm and 15 nm filaments, suggestive of actin and myosin. The cells varied in shape from elongated or flat to rounded. Maculae adhaerentes, gap junctions and basement membranes were present. It is concluded that these cells closely resemble myofibroblasts, by virtue of their cytology and behaviour. The significance of this observation, concerning hypotheses on the genesis of anterior capsular cataract is discussed.

Betaine in the treatment of homocystinuria due to 5,10-methylenetetrahydrofolate reductase deficiency

Abstract: In a 3-year-old mentally retarded girl with homocystinuria due to 5,10-methylenetetrahydrofolate reductase deficiency among different therapeutic approaches only treatment with betaine (15-20 g/day) resulted in a satisfactory biochemical response. Betaine improved homocysteine remethylation and thus lowered plasma homocystine to trace amounts and normalized the previously very low plasma methionine concentration. This biochemical response was associated with a clinical improvement although she remained mentally retarded.

Projections from the superior colliculus to a region of the central mesencephalic reticular formation (cMRF) associated with horizontal saccadic eye movements.

Abstract: Radioactive wheatgerm agglutinin (WGA) and horseradish peroxidase (HRP) were injected into portions of the mesencephalic reticular formation at sites where electrical stimulation induced either small or large contralateral horizontal saccadic eye movements. We have designated this region as the Central MRF (cMRF). It contains both cells and fiber tracts, including the efferent output of the superior colliculus (SC), destined for the dorsal tegmental decussation and the predorsal bundle. Cells labelled by WGA and HRP injections were found in the intermediate and deep layers of the superior colliculus and the adjacent central gray matter on the ipsilateral side. Injections into the dorsal cMRF, at sites where small saccades were induced, caused labelling of cells in the rostral intermediate layer of SC. Injections into the ventral cMRF, at points where large saccades were elicited, caused labelling of cells in the caudal intermediate layer of SC. The deepest layers of SC and the adjacent central gray were also labelled from the small eye movement region of dorsal cMRF. We interpret these findings to indicate that the intermediate layers of SC send axonal projections to the horizontal eye movement region of the MRF in a topographic fashion. The projection from the intermediate layer is organized so that regions in SC and cMRF related to small or to large eye movements are interconnected. The results support the hypothesis that cMRF is a topographically organized area, involved, like SC, in the control of eye movements. Since both cMRF and the superior colliculus project to areas of the pons and medulla where saccadic eye movements are produced, they could give rise to parallel pathways for the generation of contralateral saccades.

Correlation of islet cell antibodies and HLA-DR phenotypes with diabetes mellitus in adults.

Abstract: In a cross-sectional study, sera of 81 adult diabetic in-patients were tested for the presence of pancreatic islet cell antibodies (ICA), both IgG and complement-fixing. All patients had been well controlled initially with oral hypoglycaemic agents and therefore had been classified as having Type 2 (non-insulin-dependent) diabetes. However, 14 were subsequently classified as Type 1 (insulin-dependent) because they became insulin-dependent within 2 months of diagnosis. Ten of these patients (71%) were ICA-positive. Sixty-seven patients had been non-insulin-dependent for at least 1 year after diagnosis. Circulating ICA were present in 18 patients and 16 of these (89%) required insulin therapy. Secondary oral hypoglycaemic agent failure developed within a mean period of 3.7 years after diagnosis. In contrast, in the ICA-negative sub-group (n = 49) insulin treatment became necessary in 29 patients. Secondary oral hypoglycaemic agent failure of these patients had developed after a mean period of 8.4 years, which was significantly longer than in the ICA-positive patients (p< 0.01). Complement-fixing-ICA were detected only in sera with an ICA-IgG titre of at least 8, and its prevalence was similar in the sub-groups tested, i. e., the Type 1 diabetic patients and the patients with secondary oral hypoglycaemic agent failure. With HLA-DR typing, a significant excess of the DR3 antigen and heterozygous DR3/DR4 phenotypes was found in ICA-positive patients with secondary oral hypoglycaemic agent failure and in the Type 1 diabetic patients, which was comparable with the frequencies reported in juvenile-onset Type 1 diabetes. The heterozygous DR3/W6 phenotype was significantly increased in the ICA-positive patients when compared with 13 ICA-negative patients. Thus, the presence of ICA and an excess of certain HLA-DR phenotypes identify a sub-group within the adult diabetic population with secondary oral hypoglycaemic agent failure which can be regarded as a retarded form of Type 1 diabetes.

Efficacy of CW-Doppler and duplex system examinations for the evaluation of extracranial carotid disease.

Abstract: The efficacy of different ultrasound methods for the detection of extracranial arterial disease (E AD) was evaluated on the basis of the comparison with angiography. High-resolution B-scan imaging combined with a multigated pulsed Doppler flow pattern analysis (Duplex system) achieved the best results for the detection of morphological and hemodynamic changes of nonstenotic lesions and low grade stenosis. However, a technically unsatisfactory examination rate of 19%, the failure to differentiate between total and subtotal carotid occlusions, underestimation of significant stenosis and impracticable vertebral flow studies were disadvantages of the Duplex technique. CW-Doppler examinations proved to be more precise and more reliable for the detection of significant stenosis and occlusions. Since vertebral blood flow studies were impractical with the Duplex system, CW-Doppler provides more comprehensive information about the hemodynamics of cerebral blood supply.

Age-dependency of alpha- and beta-adrenoceptors on thrombocytes and lymphocytes of asthmatic and nonasthmatic children* **

Abstract: Among the possible mechanisms which may cause wheezing or asthmatic episodes a genetically determined β-adrenoceptor blockade and a hyperresponsiveness of α-andrenoceptors has been postulated. Evidence to support this hypothesis stems from an increased bronchial sensitivity to β-blockers, a reduced formation of cyclic AMP in response to β-adrenergic stimulation and enhanced α-adrenergic responses in asthmatic subjects. The recent development of techniques for measuring the specific, high-affinity binding of radiolabeled α-and β-adrenergic antagonists made it possible to study α- and β-adrenoceptors in vitro. Based upon the assumption that a change in the number and/or affinity of adrenergic receptors might be a general phenomenon, we have performed α- and β-receptor binding studies on lymphocytes and platelets from wheezing infants and asthmatic children as well as of infants, children, and adults not suffering from these diseases.

Short term acclimation of spinach to high temperatures: effect on chlorophyll fluorescence at 293 and 77 Kelvin in intact leaves.

Abstract: Using intact leaves of Spinacia oleracea (L.), reversible temperature-induced changes in chlorophyll fluorescence emitted at room temperature and at 77K were studied. Interpretation of fluorescence at 77K was largely facilitated by developing a new method to minimize reabsorption artifacts (`diluted leaf-powder9). Leaves of plants grown at 15 to 20°C were exposed for several hours to different temperatures. Upon incubation at 35°C in the dark or in the light, the following changes in 77K fluorescence occurred with a half-time of less than 1 hour: (a) the initial fluorescence ( F 0 ) of photosystem I increased by 15%, while that one of photosystem II somewhat decreased; (b) although variable fluorescence declined in both photosystems, the decrease in photosystem II (40%) was more severe; (c) the changes were less significant after 480-nanometer excitation light was replaced by 430-nanometer light. The data were interpreted in terms of a reversible, temperature-induced change in thylakoid structure and related change in the distribution of the absorbed energy in favor of photosystem I, at the expense of photosystem II excitation, probably accompanied by an increase in the rate of thermal deactivation of excited states. The considerable decrease in the variable part of room temperature fluorescence gives rise to the suggestion that this transition has lowered the reduction level of plastoquinone, i.e. has increased electron flow through photosystem I, relative to photosystem II. Possible physiological and mechanistic analogies between this temperature-induced state transition and the light-dependent state 1-state 2 regulation has been discussed.

Ultrastructural observations on the histogenesis of localized fibrous tumours of the pleura (benign mesothelioma)

Abstract: Five localized fibrous tumours of the pleura (benign mesothelioma) were studied ultrastructurally in order to elucidate their histogenesis. The histological subtypes of this benign fibrous lesion of the visceral pleura, i.e. the cellular, the collagenous, and the hyaline, were separately analysed. The tumours are composed of undifferentiated mesenchymal cells, intermediate and differentiated fibroblasts as well as collagenous interstitial tissue. The varying distribution of these cell elements account for the various histological subtypes. Morphological similarities between the mesenchymal tumour cells and the superficial mesothelial cells, which are always separated from the true tumour tissue by an intact basement membrane, were not observed. The different cellular elements can be regarded as parts of a continuous spectrum of cytodifferentiation, in which the mature fibroblasts are derived via intermediate forms from the undifferentiated cells. It is concluded that the localized fibrous tumours of the pleura arise from immature mesenchymal stem cells, which seems to be normally found in the submesothelial layer of the visceral pleura.

ELECTRONICALLY EXCITED STATES IN MICROSOMAL MEMBRANES: USE OF CHLOROPHYLL‐a AS AN INDICATOR OF TRIPLET CARBONYLS

Abstract: —Chlorophyll-a enhances the photoemission from the microsomeltert-butyl hydroperoxide system without affecting the rates of O2 uptake and lipid peroxidation. This photoemission, due to energy transfer from triplet carbonyls to microsome-bound chlorophyll-a, shows that microsomal membranes produce a significant amount of excited triplet carbonyls during lipid peroxidation.

Hepatic Glutamine and Ammonia Metabolism

Abstract: Our interest in glutamine metabolism arose from an investigation of mitochondrial NADPH/NADP+ as affected during the metabolism of ammonia in the process of ureogenesis [1, 2 ]. Glutamine served as a compound yielding ammonia plus glutamate within the mitochondria via the activity of mitochondrial glutaminase, whereas added ammonia yielded glutamate only at the expense of 2-oxoglutarate via reductive animation [3]. Clearly, such model experiments on redox compartmentation have a physiological bearing, because the effects occur at portal concentrations of ammonia and glutamine within the physiological range of about 0.3 mM and 0.6 mM, respectively [4]. Thus, this article will present the redox transitions related to this important sector of nitrogen metabolism.

Facilitation of renal function by intermittent mandatory ventilation

Abstract: The effects of intermittent mandatory ventilation (IMV) and controlled mechanical ventilation (CMV) on excretory function and the hemodynamics of the kidneys were studied in two groups of anaesthetized dogs during periods of 3 and 4 h. IMV was associated with statistically significant improved urinary output and renal plasma flow of approximately 50 and 35%, respectively. Graphical and statistical analysis revealed certain cross-over effects indicating that the beneficial effect of IMV was more pronounced if it was used following CMV. The improvements in renal function were interpreted as consequences of decreased mean intrathoracic pressures during IMV as compared to CMV. A correlation to global hemodynamic changes could not be established. IMV does facilitate kidney function and hence may successfully counteract the retention of water and salt which occurs during prolonged mechanical ventilation.

Congenital anomalies in patients with choanal atresia: CHARGE-association

Abstract: Six patients with both choanal atresia (ChA) and additional malformations are described and another 110 cases with this combination reviewed from the literature. Our study of these cases supports the existence of the CHARGE-association (Coloboma, Heart Disease, Atresia of choanae, Retarded mental development and growth, Genital hypoplasia, Ear anomalies and deafness). Our findings suggest the inclusion of orofacial clefts and oesophageal atresia among the main symptoms of this association. A certain degree of facial dysmorphism (low set, dysplastic ears, retrogenia, antimongoloid slant of palpebral fissures and anteverted nares) was observed in each of our cases. Infants with the bilateral type of ChA plus cardiac defects and those with ChA plus renal malformations have a high mortality rate. The aetiology of the association is not clear. The recurrence risk may be low.