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Biomedical subjects

D Schwarz

Publications and source records attributed to D Schwarz.

At least 55 records · Page 3Linked to original sources
PubMed1988

Preparation and properties of large octylglucoside dialysis/adsorption liposomes.

The suitability and capacity of the polystyrene resin Wofatit EP 60 for the adsorption of octylglucoside, Triton X-100, Cholate, and CHAPS was studied. Optimal detergent/bead ratios and the maximum capacity of Wofatit EP 60 for the four detergents were determined as prerequisites for optimal application of the beads in liposome preparations. It is shown that large unilamellar liposomes can be prepared easily, quickly and cost-effectively using a combined dialysis/adsorption method with octylglucoside as detergent and Wofatit EP 60 and adsorbing polystyrene beads. Structure, composition, size, homogeneity, lamellarity, stability, internal volume, and residual octylglucoside concentration were studied by gel chromatography, radioactive assay, dynamic light scattering and electron microscopy. Vesicle size and homogeneity depend on lipid concentration, lipid composition, cholesterol content, and the rate of octylglucoside removal, but not on the detergent/lipid ratio. The reliability of the method and the properties of the vesicles are compared with those of other methods and researchers.

Adsorption↗
PubMed1987

Transcomplementation of HLA genes in IDDM. HLA-DQ alpha- and beta-chains produce hybrid molecules in DR3/4 heterozygotes.

The HLA association with insulin-dependent diabetes mellitus is highest among individuals heterozygous for DR3 and DR4. To investigate potential mechanisms to account for this association, we performed two-dimensional gel-electrophoretic analysis of HLA molecules from DR3/4 heterozygous patients. These studies demonstrated hybrid molecular dimers corresponding to products of HLA-DQ genes linked to DR3 and DR4, i.e., the DQw2 and DQw3 genes, respectively. Two types of DQ molecules were found: immunoprecipitation by DQw3-specific monoclonal antibody 17.15 identified a DQw3 beta-chain associating with a DQw3 alpha-chain and a DQw3 beta-chain associating with a DQw2 alpha-chain. The identity of alpha- and beta-chains comprising these hybrid molecules was confirmed by HPLC peptide-map analysis. Several characteristic peptide peaks identified both DQw2 and DQw3 alpha-chains associated with DQw3 beta-chains. The formation of such DQ alpha (DQw2)-Dq beta (DQw3) dimers potentially contributes a direct molecular mechanism for HLA-associated contributions to disease in DR3/DR4 heterozygotes.

Diabetes Mellitus, Type 1↗
PubMed1985

Relation between the structure of benzphetamine analogues and their binding properties to cytochrome P-450 LM2.

Twelve substrates of a homologous series of tertiary amines (type I substrates) have been reacted with cytochrome P-450 LM2 incorporated into unilamellar liposomes and in soluble form. The apparent spectral dissociation constants (Ks) of the substrate enzyme complexes and the induced high-spin shifts have been correlated with the electron density of distinct carbon atoms as monitored by 13C-NMR chemical shifts, the solubility of the amines and steric parameters of the substrate molecules. The results obtained led to the conclusion that two different intrinsic properties of the substrates can be discriminated in relation to the substrate-enzyme interaction. A diminished electron density at the nitrogen atom is accompanied by an increased binding affinity. The steric structure of the respective substrate determines its capability to shift the spin equilibrium to the high-spin state. Some characteristics of the active center of the enzyme are derived from the evidenced properties of the substrates.

Animals↗
PubMed1984

Incorporation of the cytochrome P-450 monooxygenase system into large unilamellar liposomes using octylglucoside, especially for measurements of protein diffusion in membranes.

Cytochrome P-450 and NADPH cytochrome P-450 reductase were incorporated into large unilamellar lipid vesicles (200-300 nm in diameter) removing octylglucoside from mixed micelles by dialysis. The large size of the protein-containing liposomes guarantees a negligibly small vesicle tumbling. Such large vesicles are better suited for studies of protein rotation in reconstituted membranes than vesicles prepared by use of bile salts. At present the octyl-glucoside reconstituted monooxygenase system seems to be the most appropriate model for studying protein-protein and protein-lipid interactions in liver microsomes due to the similarity with respect to the main structural and functional properties, including size.

Animals↗
PubMed1984

Motional dynamics of a spin labeled substrate analogue bound to cytochrome P-450: saturation transfer EPR studies.

The rotational motion of the spin labeled substrate analogue n- propylisocyanide bound to the active center of cytochrome P-450 was studied by saturation transfer EPR. The observed motional rate characterized by an effective rotational correlation time tau R of about 40 ns at 20 degrees C is at least 3 orders of magnitude higher than the macromolecular rotational diffusion of cytochrome P-450 in the microsomal membrane and represents a considerable motion in relation to the whole enzyme molecule. The tau R value is independent on the degree of purification of the enzyme system as revealed by measurements of (1) liver microsomes, (2) partially purified cytochrome P-450, and (3) cytochrome P-450 LM2 but shows a characteristic temperature dependence in the case of microsomes resulting in breaks in the Arrhenius plot at temperatures which correspond to phase transitions of the phospholipids. The results indicate that the mobility of the bound substrate analogue reflecting a relatively high conformational flexibility of the substrate binding region which depends on the state of the lipids and can therefore be influenced by them. These results support the assumption that cytochrome P-450 is capable of forming manifold binding to substrate molecules differing in stereochemical structures because of the conformational flexibility of its binding region.

Animals↗
PubMed1984

[Vascular loop. A contributing factor to vascular cerebellopontile syndrome].

Modern diagnostic methods such as brainstem-evoked response audiometry and CT scanning with positive and negative contrast enhancement represent a major advance in the diagnostic evaluation even of small acoustic neuromas. However difficulties arise in differentiation between tumours and other cerebellopontine angle lesions, as shown by means of a case report. An arterial loop of the anterior inferior cerebellar artery (AICA) between the facial and the eighth cranial nerve was the cause of progredient neural hearing loss, peripheral vestibular dysfunction and hemifacial spasm. Vascular decompression was performed with total relief of spasm and partial restitution of hearing. In differential diagnosis of the pathology of the cerebellopontine angle region and the internal auditory canal the clinical symptoms are important.

Cerebellopontine Angle↗
PubMed1982

Mobility and clusterlike organization of liposomal cytochrome P-450 LM2: saturation transfer EPR studies.

Rotational diffusion of the electrophoretically homogenenous isozyme cytochrome P-450 LM2 from rabbit liver microsomes has been studied in buffer solution and in phospholipid vesicles by means of saturation transfer EPR spectroscopy. Sulfhydryl groups of the enzyme were selectively modified using a maleimide spin label. The effective rotational correlation time of 220 ns for the rotation of cytochrome P-450 in buffer solution is consistent with the fact that the purified free enzyme occurs as an oligomeric (6-8 monomers) aggregate. Further, the clusters rotate almost isotropically and therefore are in a first approximation spherically shaped. The effective correlation time of about 180 microseconds observed strong immobilization thus evidencing protein aggregation within the membrane. The anisotropic character of the spectra indicates a nonspherical shape and/or anisotropic rotational motion of the cluster. The results are compared with corresponding data from cytochrome P-450 in microsomal form.

Animals↗
PubMed1981

The management of squamous cell carcinoma in cervical lymph nodes in the clinical absence of a primary lesion by combined surgery and irradiation.

Sixty-three patients who had either previously treated primary tumors or unknown primary tumors and developed metastatic cervical adenopathy in their previously untreated necks received the combination of surgery and megavoltage irradiation. Within two years, 12 patients died of intercurrent disease, nine patients died with distant metastases only, and five patients had disease recur at a primary site. The remaining 37 patients were evaluable for control of neck disease; 26 patients had previous treatment to a primary head and neck cancer that was under control at the time cervical adenopathy was treated; and 11 patients had an unknown primary tumor that was believed to be in the head and neck area. The combination of pre- or postoperative irradiation and surgery controlled neck disease in 86% of the evaluable patients. Because of the extent of neck disease, these patients would have been at a high risk of failure in the treated area if only a single modality of treatment were used. Analysis of the data shows an association of extranodal connective tissue involvement with both a decreased rate of control within the treated area and distant metastases.

Carcinoma, Squamous Cell↗
PubMed1980

Analysis of phosphoryl transfer mechanism and catalytic centre geometries of transport ATPase by means of spin-labelled ATP.

Spin-labelled ATP [3'-O-(1-oxyl-2,2,5,5-tetramethyl-3-carbonyl pyrrolidine)-adenosine 5'-triphosphate], abbreviated SL-ATP, is used to study firstly the occurrence of an associative phosphorane mechanism for the phosphoryl transfer from ATP to the transport-ATPase protein, and secondly the presence of two geometrically unequal catalytic centres in the two catalytic peptide chains deduced to explain the existence of two KD'(ATP) values under equilibrium conditions and two Km(ATP) values under turnover conditions. 1. In the presence of Na+, K+ and Mg2+, SL-ATP is not hydrolysed by transport-ATPase from three different sources. In the presence of Na+ and Mg2+, SL-ATP reacts initially like ATP with the enzyme, as indicated by the production of a similar ouabain-binding protein conformation. With both nucleotides, this initial reaction includes the formation of the covalent enzyme-nucleotide complex through nucleophilic attack of the aspartate carboxyanion of the catalytic centre on the terminal phosphorus atom of the triphosphate chain. This produces the ouabain-binding conformation of the enzyme. Unlike ATP, the covalent enzyme-SL-ATP complex resists further transformation. 2. In the presence of Na+, K+ and Mg2+, the influence of SL-ATP on ATP hydrolysis by transport-ATPase depends on the ATP concentration chosen. At low ATP concentration, when the enzyme works as Na+-ATPase, SL-ATP does not affect the rate of ATP cleavage. At high ATP concentration, however, when the enzyme works as (Na+ + K+)-ATPase, SL-ATP reduces the rate of ATP hydrolysis to the level of Na+-ATPase activity, apparently due to the formation of the covalent enzyme-SL-ATP complex. 3. SL-ATP in the covalent enzyme-SL-ATP complex shows an ESR spectrum which is indistinguishable regarding the overall shape, the rotational correlation time, tau, and the hyperfine coupling constant, aN, from the ESR spectrum of free SL-ATP. Consequently, the dimensions of the catalytic centre cleft of transport-ATPase provide the labelled group of SL-ATP, opposite to its 3'-O-esterification site at the ribose moiety, in a wide-cleft groove, enough free space for an essentially unhindered rotational mobility within an aqueous environment like that of the bulk medium. Judged from literature data, similarly wide grooves exist in the catalytic centre clefts of mitochondrial and myosin ATPases. 4. In the framework of present knowledge, the idea is put forward that the structural unit forming the binding site for the AMP moiety of ATP in ATPases is similar to the structural unit forming the binding site for the AMP moiety of NAD and ADP in several dehydrogenases and kinases.

Adenosine Triphosphatases↗
PubMed1978

[Stomatological health education for children and adolescents].

Principles of dental health education is childhood and adolescence are outlined with special regard to priorities related to the age-specific state of dentition development. The paper concluded with organizational advice deduced from practical experience.

Adolescent↗
PubMed1977

[Therapy of herpes zoster through active premunization. 2. Treatment of zoster patients, results of experimental and clinical studies, treatment results].

A brief review of the previous and generally inadequate methods for the treatment of Herpes Zoster is presented. The concept of "active premunization" by appropriate inducer to provide an objective treatment is defined. A "Premunization Inducer" (PIND) based on a particular non-infectious preparation of an avian pox ("avipox") virus has been shown to enhance non-specific defence mechanisms in the host by T-cell stimulation and to inhibit virus proliferation by the induction of Interferon. The mode of action, efficacy against different viruses and the safety of the preparation is described and discussed. 114 patients with Herpes Zoster were treated with this "premunization Inducer" either orally (for buccal absorption) or by means of a nasal spray. There were no side effects and in all cases there was a marked reduction in the duration of the illness up to the shedding of the last scab (about 15 days instead of the more usual 31 days). Pain was relieved in some cases within 6 hours and in the remainder within 2 days: a rapid resolution of the inflammation could be observed. There were practically no signs of postherpetic neurological complications among the patients treated (the usual incidence of post-herpetic neuritis is around 18%). The treatment of Herpes I and Herpes II infection other viral conditions will be reported elsewhere.

Adult↗
PubMed1976

[The effect of the beta-adrenergic blocking agent propranolol in mania (author's transl)].

Six patients with the diagnosis of acute mania were treated with high doses of the beta-adrenergic blocking agent propranolol. One of these patients was treated during two manic phases. Psychopathologic change during treatment was rated daily by a psychiatrist not informed on the patients medication. The IMPS (Inpatient Multidimensional Psychiatric Scale) was used. Three cases were placebo-controlled under double blind conditions. Four times we had a second medication period, twice with propranolol and once with oxprenolol and dexpropranolol respectively. Propranolol was administered every 4 h (six times per day), starting with single doses of 20-40 mg. Doses were increased individually under control of pulse rate, blood pressure, and ECG. Augmentation of doses was continued until an effect on manic symptomatology was undoubtedly seen or until therapy had to be discontinued because of side-effects. In four patients definite improvement of manic symptomatology could be achieved during altogether five manic phases within usually two treatment periods of 5-15 days. Manic behavior disappeared completely in two of these patients. The effective dosage of propranolol varied between 280 and 2320 mg per day. All of the improved patients relapsed after discontinuation of the drug. In the only case on dexpropranolol (5 days up to 900 mg daily) the effect was questionable. No extrapyramidal side-effects were observed. In one patient treatment was discontinued because of lack of cooperation, in another because of extrasystoles. Gastrointestinal bleeding occurred in the patient who received dexpropranolol. This complication was possibly due to other medication. Other side-effects were insomnia, hypertension, precordial pain, abdominal pain as well as the expected hypotension and bradycardia. The significance of these results regarding the catecholamine hypothesis of manic-depressive illness is discussed.

Adolescent↗