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Biomedical subjects

M Mattern

Publications and source records attributed to M Mattern.

10 recordsLinked to original sources
PubMed1999

Formulation of proteins in vacuum-dried glasses. II. Process and storage stability in sugar-free amino acid systems.

The purpose of this research was to investigate the freeze- and vacuum-drying behavior of L-amino acids of current/potential use as adjuvants for formulating proteins. The analytical methods used were wide-angle x-ray diffraction, differential scanning calorimetry, and scanning electron microscopy. Protein analysis was performed either as an activity assay (lactate dehydrogenase [LDH]) or by size-exclusion chromatography (granulocyte colony-stimulating factor [rhG-CSF]). After samples were freeze-dried, only the four basic amino acids (arginine, lysine, histidine, and citrulline) formed amorphous solids, which, however, were partially crystalline. The remaining amino acids all formed fully crystalline solids. After samples were vacuum-dried, (20 degrees C, 0.1 mbar, 1 ml fill volume in 2-ml vials) fully crystalline solids were formed by all of the amino acids. For arginine, the addition of either HCl, H3PO4, or H2SO4 sufficient to form the respective salt produced amorphous solids after vacuum-drying, but they had high residual water contents and low glass transition temperatures (Tg). Addition of phenylalanine to arginine base inhibited crystallization of the latter at low concentrations during vacuum-drying procedure, leading to formation of a pure rubbery solid. At higher concentrations the phenylalanine crystallized, producing dry products with glass transition temperatures of > 60 degrees C. The process and storage stability of LDH and rhG-CSF in the vacuum-dried phenylalanine/arginine glasses was greatly improved at temperatures up to 40 degrees C compared with the unprotected proteins. Uptake of moisture during storage was, however, a complicating factor, reducing Tg, promoting crystallization, and leading to decreased protein stability. The PO4 salt of arginine produced especially high glass transition temperatures after it was vacuum-dried. These sugar-free amino acid formulations thus are potential stabilizes for proteins.

Amino Acids↗
PubMed1994

A practical approach to TQI.

Total quality improvement (TQI) is a refreshing new approach to leadership that can be applied to a dialysis setting. The team approach to prospective data analysis is used for problem solution and reevaluation. Adapting theory to daily practical application can be successfully done using time, energy, and full senior management commitment. Staff education and involvement are essential to successful program implementation. Evaluation tools are easily adapted to analyze common dialysis problems. The initial time invested in education and data collection can be great but results in a streamlined process.

Hemodialysis Units, Hospital↗
PubMed1989

Stimulation of intracellular topoisomerase I activity by vasopressin and thrombin. Differential regulation by pertussis toxin.

Incubation of cultured rat aortic smooth muscle cells (A-10, ATCC CRL 1476) with [8-arginine]vasopressin (AVP) or thrombin increased the amount of DNA strand breakage induced by camptothecin, an inhibitor of topoisomerase I (DNA topoisomerase; EC 5.99.1.2) and transiently stimulated the extractable activity of this enzyme. Both topoisomerase-related responses were prevented by treatment of the cells with AVP or thrombin plus the appropriate receptor antagonist. The increase in strand breakage mediated by AVP and thrombin depended on the concentration of hormone. Neither AVP nor thrombin had any effect on strand breaks obtained with the epipodophyllotoxin VM-26, an inhibitor of topoisomerase II [DNA topoisomerase (ATP-hydrolysing); EC 5.99.1.3]. Pretreatment of the cells with pertussis toxin partially inhibited thrombin-mediated increases in camptothecin-induced strand breakage whereas AVP-mediated increases were unaffected. These results are consistent with the notion that AVP and thrombin induce a transient increase in intracellular topoisomerase I activity via interactions with their respective cell surface receptors and that the effects of the activation of these receptors are mediated by different G-proteins.

Animals↗
PubMed1989

The signal transduction system of the leukotriene D4 receptor.

During the past several years, substantial progress in understanding the receptors and signal transduction processes for peptidyl leukotrienes has been reported. Receptors have been identified and characterized, the major steps in the signal transduction pathway have been described, and the genetic and epigenetic regulatory processes have been characterized. Very recent studies have defined the mechanisms by which LTE4 acts as a partial agonist at the LTD4 receptor. The cloning of the genes for the proteins involved in the major steps of the signalling process has also been initiated. Stanley Crooke and co-authors summarize this recent progress and present their current notions about the LTD4 receptor signalling process.

Animals↗
PubMed1986

Isolation of intercalator-dependent protein-linked DNA strand cleavage activity from cell nuclei and identification as topoisomerase II.

DNA intercalating agents such as 4'-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA) have previously been found to induce in mammalian cells the formation of protein-associated DNA single- and double-strand breaks. In the current work, an activity characterized by the production of DNA-protein links associated with DNA strand breaks and by stimulation by m-AMSA was isolated from L1210 cell nuclei and was shown to be due to topoisomerase II. Nuclei were extracted with 0.35 M NaCl, and the extract was fractionated by gel filtration, DNA-cellulose chromatography, and glycerol gradient centrifugation. A rapid filter binding assay was devised to monitor the fractionation procedure on the basis of DNA-protein linking activity. The active DNA-cellulose fraction contained both topoisomerase I and topoisomerase II whereas the glycerol gradient purified material contained only topoisomerase II activity. The properties of the active material were studied at both stages of purification. m-AMSA enhanced the formation of complexes between purified topoisomerase II and SV40 DNA in which the DNA sustained a single- or double-strand cut and the enzyme was covalently linked to the 5' terminus of the DNA. This action was further enhanced by ATP, as well as by nonhydrolyzable ATP analogues. m-AMSA inhibited the topoisomerization and catenation reactions of topoisomerase II, probably because of trapping of the enzyme-DNA complexes. The activity showed a dependence on the type of DNA intercalators used, analogous to what was previously observed in intact cells. m-AMSA had no effect on topoisomerase I.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

[Experimental trypanosomiasis in rabbits infected by Trypanosoma equiperdum: some aspects of immune response and coagulation disorders (author's transl)].

Some aspects of immune response and coagulation disorders are investigated on rabbits infected by two strains of Trypanosoma (Trypanozoon) equiperdum giving diseases with different clinical expression. The study of antibodies to trypanosomes emphasizes the high immunogenicity of specific antigenic type glycoprotein, antigenicity of which seems to inhibit common antigens expression. Significant increase of anti-fibrinogen antibodies is discussed in relation with the presence of autoantibodies frequently discovered along trypanosomiasis. As IgM they contribute to the classical hypermacroglobulinemia of these diseases. Their casual contribution in the contribution in the casual contribution in the observed disorders is argued. The meaning of fibrinolytic system activation which is shown by FDP significant increase is equally argued: secondary fibrinolysis or Hageman Factor activation mediated by immune complexes.

Animals↗