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Biomedical subjects

H Outzen

Publications and source records attributed to H Outzen.

7 recordsLinked to original sources

Purification and characterization of pancreatic elastase from North Atlantic salmon (Salmo salar).

An elastase I-like enzyme was purified to homogeneity from the pyloric caeca of North Atlantic salmon (Salmo salar) and compared with porcine elastase I. The molecular weight and isoelectric point were estimated to be 27 kDa and over 9.3, respectively. The pH optimum was between 8.0 and 9.5, and the enzyme was unstable at pH values below 4. Kinetic properties examined using Suc-(Ala)3-p-nitroanilide showed that the catalytic efficiency of salmon elastase was about 2.5 times higher than that of porcine elastase. Furthermore, the salmon enzyme was less stable at lower pH values and temperatures than the porcine enzyme. The preference for amino acids at the primary binding site was found to be different from that of the porcine elastase. The salmon elastase binding pocket seems to prefer more branched aliphatic residues than the porcine elastase.

Animals↗

Temperature and pH sensitivity of trypsins from Atlantic salmon (Salmo salar) in comparison with bovine and porcine trypsin.

Four differently charged trypsins were purified from pyloric caeca of Atlantic salmon (Salmo salar). The isoelectric points of three anionic isoforms were 4.70, 4.60, and 4.55 (anionic trypsin I, II and III, respectively). And for the first time a cationic isoform (isoelectric point above 9.3) has been isolated from a marine species. The apparent molecular weights of all four isoforms were about 25 kDa as determined by SDS-PAGE. The salmon enzymes were inhibited by serine proteinase inhibitors in general and also by specific trypsin inhibitors. Anionic trypsin I and the cationic isoform were further examined. Anionic trypsin I showed the typical cold-adaptation features, low pH and temperature stability (also lower Gibb's free energy of GdnHCl-induced unfolding) and high catalytic efficiency as compared to the mammalian trypsins. The cationic isoform did not show these features, but resembled the mammalian trypsins.

Animals↗

Human immunodeficiency virus infection of human lymph nodes in the SCID-hu mouse.

The SCID-hu mouse is a small animal in which human hematolymphoid organs can be engrafted and maintained in vivo. In this study, parameters are described for reproducible infection of SCID-hu mice after i.v. inoculation. Infection was found to be dependent upon the time after inoculation, the virus isolate, the titer of virus, and the human target organ implanted into the mouse. Ten to 14 days after the i.v. administration of HIV isolates derived freshly from patients (e.g., JR-CSF, JR-FL, SM), 100% of engrafted human lymph nodes in SCID-hu mice were infected; greater than 95% of these animals were also viremic. Implants of human thymus or connective tissue, as well as the endogenous murine hematolymphoid organs, were not infected. As demonstrated by a combination of in situ hybridization and immunohistochemistry, both T-lymphoid and myelomonocytic lineage cells were infected in this system. HIV isolates that have been adapted to growth in vitro (e.g., HTLV-IIIb) were not infectious. When either 3'-azido-3'-deoxythymidine (AZT) or 2',3'-dideoxyinosine (ddIno) was administered to SCID-hu mice before HIV infection, the animals were protected in dose ranges similar to those used in man. This animal model may now be used as an efficient intermediate step between the lab and the clinic to study the infectious process in vivo and to best select efficacious antiviral compounds against HIV.

Animals↗

Prognostic determinants in conventionally treated myocarditis and perimyocarditis--focus on antimyolemmal antibodies.

In this study from two specialized centres 85 patients with histologically proven myocarditis (n = 10) and clinically ascertained perimyocarditis (pericardial effusion and cardiomegaly or segmental wall motion abnormality; n = 75) were followed up for 4.5 + 1.9 years. Immunosuppressive treatment was not applied. After a mean follow-up period of 4.5 + 1.9 years 55% of patients had improved clinically and 35% of patients were completely free of symptoms. Relapses had occurred up to three times. Chronic forms were found in 20% of patients, mostly in those with pericarditis and effusions. Eighteen percent of the patients deteriorated gradually. In 20% of the chronic or deteriorating patients congestive heart failure developed (postmyocarditic heart muscle disease). Fifteen percent of the patients died, mainly from bacterial perimyocarditis and to a lesser extent from inflammatory heart disease from enteroviruses. Patients who succumbed after more than 6 months died either suddenly or from progressive heart failure. A favourable outcome was often accompanied by a decrease in titre, but this decrease was less impressive in those who had antimyolemmal and antisarcolemmal antibodies. The persistence of these antibodies in high titres predominated in patients with poor prognosis and postmyocarditic dilated heart muscle disease, as did cytolytic serum activity.

Autoantibodies↗

The SCID-hu mouse: a small animal model for HIV infection and pathogenesis.

The SCID-hu mouse is a heterochimeric small animal model designed to support hematopoietic differentiation and function in vivo. Multiple organs of the human hematolymphoid system have been successfully engrafted into the immunodeficient C.B-17 scid scid mouse, including fetal liver, thymus, lymph node, and skin. Co-implantation of human fetal liver and human fetal thymus results in long-term, multilineage human hematopoiesis in vivo. Mature human lymphocytes within the SCID-hu mouse are phenotypically and functionally normal. HIV infection of the SCID-hu mouse reflects a tropism similar to that found in humans: only human organs with CD4+ cells are infected. Viral replication can thereafter be monitored with assays that are safe, reproducible, and quantitative. Given this small animal model, it is now possible to study systematically the infective process of HIV and to address questions about the efficacy of novel antiviral compounds or vaccines in vivo.

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