PubMed Health⌕ Search

Biomedical subjects

Mikkel Faurschou

Publications and source records attributed to Mikkel Faurschou.

5 recordsLinked to original sources
PubMed2006

Prognostic factors in lupus nephritis: diagnostic and therapeutic delay increases the risk of terminal renal failure.

OBJECTIVE: To evaluate the prognostic significance of clinical and renal biopsy findings in an unselected cohort of patients with systemic lupus erythematosus (SLE) and nephritis. METHODS: Ninety-one patients with lupus nephritis were included in the study. Renal biopsies were classified according to the WHO criteria and examined for the presence of active and chronic histological changes. Predictors of endstage renal disease (ESRD) were identified by univariate and multivariate analyses. RESULTS: The median followup time was 6.1 years (0.1-30.0 yrs). In all cases, immunosuppressive treatment was initiated or intensified within one month following renal biopsy. The cumulative incidence of ESRD after 1, 5, and 10 years was 3.5%, 15%, and 17%, respectively. A variety of clinical and biopsy findings including several histological markers of chronic renal damage were identified as univariate predictors of ESRD. In multivariate regression analyses, duration of nephritis symptoms > 6 months prior to biopsy, s-creatinine > 140 micromol/l, diffuse proliferative glomerulonephritis, and tubular atrophy emerged as the strongest combination of independent risk factors (relative hazard ratios: 9.3, 5.6, 8.9, and 3.1, respectively). CONCLUSION: Our results confirm the negative prognostic impact of hypercreatininemia, class IV histopathology, and tubular atrophy in lupus nephritis. Our data show that delay between onset of nephritis and renal biopsy constitutes an important risk factor of ESRD. Patients with SLE should have kidney biopsy as soon as clinical signs of nephritis are evident in order to accelerate treatment decisions and minimize risk of inflammation-induced irreversible kidney damage.

Adolescent↗
PubMed2005

Prodefensins are matrix proteins of specific granules in human neutrophils.

Defensins are potent antimicrobial and proinflammatory peptides. The human neutrophil defensins human neutrophil peptide (HNP)-1-3 are synthesized as 94 amino acide (aa) preproHNPs, which are converted to 75 aa proHNPs by cotranslational removal of a 19 aa endoplasmic reticulum signal peptide. At the promyelocytic stage of myelopoiesis, proHNPs are further proteolytically modified and accumulate in azurophil granules as 29-30 aa HNPs. In contrast, proHNPs produced by more mature myeloid cells are not subjected to proteolytic cleavage and undergo a high degree of constitutive exocytosis. The proHNPs are devoid of antimicrobial potential, and the significance of their secretion is unknown. To investigate whether mature neutrophils contain proHNPs, we developed antibodies against proHNP-1 by DNA immunization of rabbits. In addition, antibodies against the 45 aa proHNP pro-piece were raised by conventional immunization procedures. These antibodies allowed detection of proHNPs in homogenates of peripheral blood neutrophils. The proHNPs were isolated by affinity chromatography, and their identity was confirmed by mass spectrometry and N-terminal aa sequence analysis. Finally, the neutrophil proHNPs were identified as novel matrix proteins of specific granules by subcellular fractionation experiments, release studies, and immunoelectron microscopy. Thus, human neutrophils not only store large amounts of mature defensins in azurophil granules but also contain a more easily mobilized reservoir of unprocessed prodefensins in specific granules.

Antibodies↗
PubMed2003

Neutrophil granules and secretory vesicles in inflammation.

The neutrophil is a major effector cell of innate immunity. Exocytosis of granules and secretory vesicles plays a pivotal role in most neutrophil functions from early activation to the destruction of phagocytosed microorganisms. Neutrophil granules contain a multitude of antimicrobial and potentially cytotoxic substances that are delivered to the phagosome or to the exterior of the cell following degranulation. This review summarises current knowledge of granule biology and highlights the effects of neutrophil degranulation in the acute inflammatory response.

Cell Degranulation↗
PubMed2002

Defensin-rich granules of human neutrophils: characterization of secretory properties.

The various granule subtypes of the human neutrophil differ in propensity for exocytosis. As a rule, granules formed at late stages of myelopoiesis have a higher secretory potential than granules formed in more immature myeloid cells. Neutrophils contain four closely related alpha-defensins, which are stored in a subset of azurophil granules. These defensin-rich azurophil granules (DRG) are formed later than defensin-poor azurophil granules, near the promyelocyte/myelocyte transition. In order to characterize the secretory properties of DRG, we developed a sensitive and accurate ELISA for detection of the neutrophil alpha-defensins HNP 1-3. This allowed us to quantify the exocytosis of alpha-defensins and markers of azurophil (myeloperoxidase), specific (lactoferrin) and gelatinase (gelatinase) granules from neutrophils stimulated with different secretagogues. The release pattern of alpha-defensins correlated perfectly with the release of myeloperoxidase and showed no resemblance to the exocytosis of lactoferrin or gelatinase. This finding was substantiated through subcellular fractionation experiments. In conclusion, despite a distinct profile of biosynthesis, DRG are indistinguishable from defensin-poor azurophil granules with respect to exocytosis. Thus, in contrast to peroxidase-negative granules, azurophil granules display homogeneity in their availability for extracellular release.

Antibodies↗