[Synthesis of N-(2-carboxy-thieno(2,3-b)pyridin-3-yl)amidines by means of reaction of 4-oxo-4H-pyrido(3',2':4,5)thieno(3,2-d)-1,3-oxazines with primary aliphatic amines].

The title compounds were synthesized by the reaction of tricyclic compounds of structure B with primary aliphatic amines under different conditions and useful isolation methods in good yields. These compounds showed an acceptable antianaphylactic activity.

[Synthesis of N-(2-carboxy-thieno(2,3-b)pyridin-3-yl)-amidines by the reaction with 4-oxo-4H-pyrido(3',2':4,5)-thieno(3,2-d)-1,3-oxazines with secondary cycloaliphatic amines].

4-Oxo-4H-pyrido[3',2':4,5]thieno[3,2-d]1,3-oxazines react with secondary cycloaliphatic amines to give besides the expected bisamides the amine salts of N-(2-carboxy-thieno[2,3-b]pyridine-3-yl)amidines. These compounds showed inhibitory activity against different lipoxygenases, but a small chemical stability.

[Immunologic studies in patients with dilated cardiomyopathy].

In 10 cases of dilated cardiomyopathy the HLA-loci (A, B, C, DR) and marker expression on lymphocytes were studied. In this group the T4/T8-ratio was decreased and interleukin-2-expression was increased in relation to normals or patients with chronic coronary heart disease, respectively. 9 patients had the HLA-A1 or HLA-A2-locus in their siblings.

[The use of bead cellulose for controlled drug liberation. 5. Kinetics of liberation of bonded drugs from bead cellulose and bead cellulose derivatives].

Examination of in vitro liberation of prazosin hydrochloride and benzocaine from formulations of matrix type with bead cellulose and bead cellulose derivatives shows deviations from first order kinetics owing to competition of several processes: dissociation of ionic bonds or cleavage of covalent bonds between drugs and bead cellulose, pore diffusion, dissolution of the drugs and swelling of cellulose matrix. Suitable combinations of different bonded portions of the drug on bead celluloses let these complexes seem to be successful in the use for controlled and retarded liberation of drugs.

[The use of bead cellulose for controlled drug liberation. 5. Binding of benzocaine as a model drug to dialdehyde-bead cellulose and its in vitro liberation].

In the case of ionic binding of drugs to bead cellulose and its derivatives there was no pronounced retardation obvious. Because of this lack benzocaine as a model drug was covalent bound to dialdehyde bead cellulose by an azomethine bond in analogy with enzyme immobilisation methods. The rate of liberation in phosphate buffer was low and incomplete compared with the dissolution rate of pure benzocaine under the same conditions.

Purification of pro- and eukaryotic superoxide dismutases by charge-controlled hydrophobic chromatography.

The process of purifying superoxide dismutases was simplified using charge-controlled hydrophobic chromatography on 10-carboxydecyl Sepharose. In only one chromatographic step following ammonium sulphate precipitation, Fe-containing superoxide dismutase from Pseudomonas putida and Cu,Zn-containing superoxide dismutase from bovine erythrocytes were purified with an overall yield of about 70% to electrophoretic homogeneity. The specific activities of the crystalline enzyme preparations were expressed in McCord and Fridovich units and were 3000 and 3200 U/mg, respectively.

Kinetics of enzymatic lysis, formation and regeneration of protoplasts ofCandida (Torulopsis) apicola.

The optimal conditions for protoplast formation ofCandida apicola were by using an enzyme fromArthrobacter sp. in combination with 2-mercaptoethanol. The kinetic data support the two-layered structure model of cell wall for this yeast but the structure of the cell wall depended on the age of cells and culture conditions.

[Histochemical investigations on the localization of acetylcholinesterase in the kidney of selected vertebrates].

The light and electron microscopical localization of AChE activity in the kidney of selected vertebrates was studied using the method of Karnovsky and Roots (1964) for light microscopy and the modification of the Koelle and Friedenwald's technique according to Tsuji (1974, 1984) for electron microscopy. AChE activity could be demonstrated light microscopically mainly within the glomeruli of some mammals (golden hamster, mouse, rat) and non-mammalian vertebrates (carp, frog). No activity was found in the glomeruli of guinea pig, of chicken and tortoise.

[The use of bead cellulose for controlled drug liberation. 4. Binding of bead cellulose and bead cellulose-derivatives with prazosin hydrochloride and its liberation].

Pure bead cellulose and the ionic derivatives carboxymethyl and dihydrogen phosphate bead cellulose were coupled with prazosin hydrochloride. The degree of substitution achieved during loading mostly depends on the number of functional groups, what was verified by titrimetric determination of the ion exchange capacity. Because of predominant ionic binding of the protonated prazosin cation to the anionic groups of several types of bead cellulose in electrolytes containing liquids as well as in water a large amount of bonded drug is liberated considerable fast.

[The use of bead cellulose for controlled drug liberation. 3. The ion exchange capacity of bead cellulose and bead cellulose derivatives].

Methods are represented for the preparation of the ionic derivatives dihydrogen-phosphate bead cellulose and carboxymethyl bead cellulose from pure, swollen bead cellulose. The degree of substitution can be varied by changing the extent of swelling of the parent bead cellulose and the amount of reactant. The products exhibit similar physical properties (swelling weight, porosity, bed volume and spherical shape) like pure, unsubstituted bead cellulose.

The specificity of chymotrypsin. A statistical analysis of hydrolysis data.

From the literature we collected all available quantitative data on the chymotrypsin-catalyzed hydrolysis of series of amino acid and peptide substrates. Utilizing this data base, we performed calculations on their quantitative structure/activity relationship (QSAR). The substrates were considered to be composed of fragments; log(kcat/Km) values for the substrates resulted from additive contributions of their fragments.

[New heterocyclic systems for thiophene-2-thiolates--synthesis and biological activity].

Dicyanketendithiolae reacts with equimolar amounts of halogenmethans, substituted with electron withdrawing groups, to give thiophene-2-thiolates. These compounds are used for the preparation of thieno[2,3-b]thiophenes, including several functional groups in 2- and 5-position. Anellation of 1,3-oxazin-, pyrimidin-, 1,2,3-triazin- or 1,4-oxazepin-cycles give hitherto unknown tri- and tetracyclic ring systems.

[Synthesis and pharmacologic testing of 1-oxo-pyridazine and 1-oxo-phthalazine-2-acetic acid derivatives].

The title compounds, starting from variously substituted beta-benzoylpropionic or beta-benzoylbenzoic acids, were prepared by cyclocondensation with alpha-ethylhydrazinoacetate monohydrochloride and subsequent alcaline hydrolysis or aminolysis of the 2-carbethoxymethyl-1,2,5,6-tetrahydro-1-oxo-pyridazines or 1,2-dihydro-1-oxo-phthalazines respectively. The 1-oxo-phthalazines 42 and 34 have a weak anticonvulsive effect. Like a large number of the other synthezized compounds, they show a central sedative component and are relatively nontoxic.

Selective and rapid solubilization of the microbial membrane enzyme aldehyde dehydrogenase.

An improved solubilization procedure for the membrane-bound quinoprotein aldehyde dehydrogenase from Acetobacter rancens CCM 1774 was established. After the first solubilization of membrane enzymes by Brij 35 which provided important extraction of membrane proteins other than aldehyde dehydrogenase, the application of Trition X-100 resulted in an almost 20-fold purification of quinoprotein aldehyde dehydrogenase. The optimal solubilization was closely connected with definite detergent/protein ratios.

[Initial experiences in diagnosis of graft rejection following clinical heart transplantation. Detection of graft-directed activated T-cells].

The binding of antigen-loaded carrier to mononuclear cells of heart transplant recipients has been investigated by means of an antigen-specific rosette technique. The increase of rosette forming cells and the inhibition of this reaction with monoclonal antibodies against activated T-cells is a sign of a beginning rejection. 3-6 days later infiltrating immunological competent cells are seen in biopsy.

[Interleukin 1 and hematopoiesis].

Interleukin-1 mediates a broad spectrum of activities in the functional network of cytokines. In addition to its function as an inducer of the acute phase response IL-1 has many effects on hemopoiesis in normal and hematologically impaired organisms. This regulatory function is realized by its ability to stimulate the release of hematopoietic growth factors and by its recruiting property for cell cycles of different hemopoietic progenitors and stem cells.

[Synthesis of 3-cyano-6-methyl-4-pyridyl-2(1H)-pyridinethiones as well as 2-substituted 6-methyl-4-pyridyl-pyridine-3-carbonitriles and 3-carbonic acid amides, respectively, and testing their cardiovascular activity].

By the base catalyzed reaction of our previously described 3-cyano-6-methyl-4-pyridyl-2(1H)-pyridinethiones 1 and 2, respectively, with branched and unbranched, respectively, alkyl, aralkyl-, alkinyl-, hydroxyalkyl-, ethoxycarbonyl- and carbamoylalkylhalides the new in 2-position substituted 6-methyl-4-pyridyl-pyridine-3-carbonitriles 15-30 were formed. By means of oxidation of the 2-methylthio-substituted pyridine-3-carbonitriles 3 and 4 with potassium periodate and potassium permanganate in diluted acetic acid, respectively, the sulfinyl compounds 5 and 6, respectively, and the sulfonyl compounds 7 and 8, respectively, were prepared. By heating of 3 and 4, respectively, with concentrated sulphuric acid the 2-methylthio-pyridine-3-carboxamides 9 and 10 were obtained.

[Secondary follicles in the thymus. Immunohistologic characterization of B lymphocytes using monoclonal antibodies].

Studies were conducted into the incidence of secondary follicles in individuals without autoimmune disease. Thymic tissue specimens were obtained from 20 children, aged between 6 months and 14 years who had undergone cardiac surgery and had been chosen at random. These specimens were immunohistologically investigated, using monoclonal anti-B cell antibodies (CD19 to CD23, CD37) and anti-immunoglobulin antibodies.

[Determination of the activity of superoxide dismutase in terms of rea substrate conversion].

On the basis of photochemical generation of O2.- and the tetrazolium/formazan system as indicating reaction an assay for SOD was developed which allows the determination of initial rate velocities of the enzyme. This was achieved by a special apparatus yielding the continuous registration of product formation simultaneously with the photochemical generation of O2.

[One-step synthesis of 2-aminothieno [2,3-d]thiazen-4-ones in some cases 5,6-anellated from ethyl 2-benzoylthioureidothiophen-3-carboxylates and evaluation of their anti-allergy activity].

The cyclization of ethyl 2-benzoylthioureidothiophen-3-carboxylates under basic conditions is known to give 2-thioxothieno[2,3-d]pyrimidin-4(1H, 3H)-ones. On the other hand, we have found that ethyl 2-benzoylthioureidothiophen-3-carboxylates 10-16 on treatment with concentrated sulphuric acid or polyphosphoric acid/ethanol undergo cyclization to give the new 2-aminothieno[2,3-d][1,3]thiazin-4-ones 17-23, in some cases 5,6-anellated. Reaction of 10-16, which are readily available from ethyl 2-aminothiophen-3-carboxylates 3-9 and benzoyl isothiocyante affords the title compounds 17-23 in good yields.

[Synthesis of N-alpha-(arylsulfonyl)-4-amidino-phenylalanyl-prolines and N-alpha-(arylsulfonylglycyl)-4-amidino-phenylalanyl-prolines and testing of them as inhibitors of serine proteinases. 33. Synthetic inhibitors of serine proteinases].

The headline compounds were prepared by the reaction of N alpha-(arylsulfonyl)- and N alpha-(arylsulfonylglycyl)-4-cyanophenylalanines to the L- and D-proline derivatives. These compounds were transformed in a usual manner in the amidino compounds. The substitution of the pyrrolidine residue by L-proline in this type of inhibitors decreased the activity against serine proteases, especially against thrombin.