| 1. |
- Björck, Lars, et al.
(författare)
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Bacterial growth inhibited by a synthetic inhibitor based upon the structure of a human proteinase inhibitor
- 1989
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 337:6205, s. 385-386
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Tidskriftsartikel (refereegranskat)abstract
- Cysteine proteinases are important not only in the intracellular catabolism of peptides and proteins1 and in the processing of prohormones and proenzymes2,3, but also in the penetration of normal human tissue by malignant cells4 and possibly microorganisms5, including viruses. Cystatin C is a human cysteine proteinase inhibitor present in extracellular fluids6. We have synthesized peptide derivatives mimicking the proposed proteinase-binding centre of cystatin C7 and find that they irreversibly inhibit cysteine proteinases. Several bacteria produce proteinases, so we tested a tripeptide derivative (Z-LVG-CHN2) for in vitro anti-bacterial activity against a large number of bacterial strains belonging to thirteen different species. It was found to inhibit specifically the growth of all strains of group A streptococci. The susceptibility of these human pathogens to the peptide was compared with that to well-established anti-streptococcal antibiotics such as tetracy-cline and bacitracin. Moreover, the peptide was active in vivo against group A streptococci: mice injected with lethal doses of these bacteria were cured by a single injection of Z-LVG-CHN2. The cysteine proteinase produced by group A streptococci was isolated and found to be inhibited by Z-LVG-CHN2; moreover, excess proteinase relieved the growth inhibition caused by the peptide derivative, suggesting that the antibacterial activity of Z-LVG-CHN2 is due to inhibition of this cysteine proteinase. This strategy of blocking proteinases with peptide derivatives that mimic naturally occurring inhibitors could be useful in the construction of new agents against other microorganisms, including viruses.
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| 2. |
- Löfberg, Helge, et al.
(författare)
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Demonstration and classification of amyloidosis in needle biopsies of the kidneys, with special reference to amyloidosis of the AA-type
- 1987
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Ingår i: APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. - : Wiley. - 0108-0164. ; 95A:1-6, s. 357-363
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Tidskriftsartikel (refereegranskat)abstract
- To examine whether sequence-specific antibodies directed against serum amyloid A were useful in the demonstration and classification of amyloidosis, needle biopsy specimens from the kidneys of 152 cases with renal disorders were investigated using the avidin-biotin-peroxidase complex technique of immunohistochemistry. A distinct immunoreactivity of protein AA was seen in biopsies from all 42 individuals who were clinically classified as having the AA-type of amyloidosis. The stained areas coincided with deposits stained by Congo red. Four of these cases demonstrated immunoreactivity of both protein AA and light immunoglobulin chains and all biopsies except one showed immunoreactivity for the amyloid P-component. After treatment with potassium permanganate, the amyloid deposits in the biopsies of all 42 cases lost their affinity for Congo red. Ten patients with clinical and laboratory findings compatible with the AL-type of amyloidosis were also investigated. All their biopsies demonstrated Congophilic amyloid deposits but none of them showed any immunoreactivity of protein AA. Amyloid deposits of lambda light immunoglobulin chains-but not kappa-were demonstrated in biopsies from four patients. The amyloid P-component was found in biopsies from six individuals and positive Congo red staining after treatment with potassium permanganate was seen in biopsies from four of the cases. Biopsies of 100 patients suffering from non-amyloid renal disorders were also examined. None of them displayed any immunoreactive deposits of protein AA. The investigation shows that amyloid deposits of the AA-type can be identified in needle biopsies when sequence-specific antibodies against serum amyloid A are used in the avidin-biotin-peroxidase complex technique. Both the diagnostic sensitivity (42 of 42) and specificity (110 of 110) of the assay were optimal (1.0). The method was found to be superior to other investigated techniques and useful for classifying amyloidosis in formalin-fixed renal biopsies.
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| 3. |
- Agardh, Carl-David, et al.
(författare)
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Lack of relationship between beta-hexosaminidase activity and retinopathy in insulin dependent diabetics
- 1987
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Ingår i: Clinica Chimica Acta. - : Elsevier BV. - 0009-8981. ; 167:1, s. 37-42
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Tidskriftsartikel (refereegranskat)abstract
- Beta-hexosaminidase activity in plasma and urine was measured and compared in insulin dependent diabetics (IDDM) with and without proliferative retinopathy. No difference in the activity of beta-hexosaminidase was found between the two groups indicating that this enzyme is not involved in the development of diabetic microangiopathy.
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| 4. |
- Kumlien, Johan, et al.
(författare)
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Urinary excretion of a glucose-containing tetrasaccharide. A parameter for increased degradation of glycogen
- 1988
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Ingår i: Clinica Chimica Acta. - : Elsevier BV. - 0009-8981. ; 176:1, s. 39-48
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Tidskriftsartikel (refereegranskat)abstract
- The urinary excretion of a glucose-containing oligosaccharide, Glc alpha[1-6Glc alpha[1-4Glc alpha[1-4Glc, (Glc4) has been measured in various physiological and pathological conditions. The Glc4 content of 24 h samples from the same individual was relatively constant, whereas 2 h samples showed up to 4-fold variations in Glc4 concentration. This variation is associated mainly with increased excretion of Glc4 after meals. A carbohydrate-rich diet, starvation or a protein-rich diet, and intense physical activity all affected the urinary excretion of Glc4. Both oral and intravenous administration of glycogen in a Rhesus monkey resulted in increased excretion of Glc4. When Glc4 itself was injected intravenously in small amounts renal clearance was rapid and complete. In contrast, injection of a larger amount resulted in incomplete (approximately 10%) renal clearance, probably due to uptake and metabolism of the oligosaccharide. In patients with glycogen storage diseases, certain malignancies, and pancreatitis, 24 h urinary Glc4 excretion exceeded the normal range. The diagnostic implications of these observations deserve evaluation. The results presented suggest a need for standardization of nutritional status and physical activity when monitoring urinary Glc4 excretion for diagnostic purposes.
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| 5. |
- Sjögren, Anders, et al.
(författare)
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Evaluation of zinc status in subjects with Crohn's disease
- 1988
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Ingår i: Journal of the American College of Nutrition. - 0731-5724. ; 7:1, s. 57-60
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Tidskriftsartikel (refereegranskat)abstract
- Zinc status was evaluated in 30 subjects with Crohn's disease. Intestinal resection had previously been performed in 23 of the subjects. The concentrations of zinc were determined in plasma, erythrocytes, percutaneous muscle biopsies, and in urine collected during 24 hours. The results were compared with those in 19 healthy controls. Most of the patients had a normal zinc status. The levels of zinc were, however, reduced (i.e., less than mean −2 SD for controls) in plasma for five, in erythrocytes for two, and in muscle biopsies for six subjects with Crohn's disease. The mean concentrations of zinc in plasma and erythrocytes were reduced (P less than 0.05), whereas the mean content of zinc in muscle biopsies and the mean urinary excretion of zinc were not significantly different, in subjects with Crohn's disease. The various zinc parameters did not correlate to each other. The results indicate that some subjects with Crohn's disease had an intracellular zinc depletion, which, however, was not reflected by a reduction in levels of zinc in plasma.
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