PubMed · 4571866
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G Tisman. 1973. Constipated lymphocytes.. https://doi.org/10.7326/0003-4819-78-3-453
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Traditional theories of enzyme kinetics do not model the influences of rapidly changing and nonisotropic enzyme concentrations in real-world systems. We have modeled local enzyme concentrations in space and time following quantal release of human leukocyte elastase (HLE) from cytoplasmic granules of polymorphonuclear neutrophils (PMN). Calculations from first principles indicate that approximately 67,000 molecules of HLE are stored in each azurophil granule at a mean concentration of 5.33 mM, which exceeds pericellular inhibitor concentrations in vivo by nearly 3 orders of magnitude. Diffusion analysis predicts obligate catalytic activity (excess of local enzyme over inhibitor concentration) that extends to 1.33 microns from the site of granule extrusion (7.8-fold larger than the mean radius of the granule), with a duration of 12.4 ms, when the pericellular concentration of alpha 1-antitrypsin equals that of normal plasma. In contrast, when PMN are bathed in alpha 1-antitrypsin concentrations found in plasma from individuals with alpha 1-antitrypsin deficiency, the radius and duration of obligate catalytic activity are increased 2.5-fold and 6.2-fold, respectively. These simulations agree remarkably well with our recent direct observations and provide a novel, nonoxidative mechanism by which quantum bursts of extracellular proteolytic activity occur despite proteinase inhibitors in the bathing medium. Titration of local enzyme-inhibitor concentration is the dominant determinant of the size and duration of such events. This construct provides new insights into the pathogenesis of tissue injury in alpha 1-antitrypsin deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)
A melanotic paraganglioma occurred in a 57-year-old woman, located in the left paravertebral space of the upper mediastinum. It was totally resected. During a 5 year follow up period neither tumour recurrence nor metastasis were observed. Histological examination of the tumour revealed a paraganglioma with monomorphous chief cell like elements which were arranged in a "zellballen" pattern. Immunohistochemical results also were in accordance with the diagnosis since neuron-specific enolase, chromogranin and synaptophysin were found in tumour cells whereas keratin was not. Additionally, neurosecretory granules were found in tumour cells during electron microscopy. A peculiar feature of the tumour was its strong pigmentation due to melanin located within the tumour cells and tumour associated melanophages. The simultaneous expression of functional properties of two different neural crest derived cells in one tumour stresses the close relationship between all neural crest elements and is in accordance with the observation of other melanotic, non-melanomatous tumours.
Granules consisting of periodically arranged membranous lamellae and amorphous electron-opaque material, i.e., periodic lamellar granules, are present in human neutrophils. To date, no extensive ultrastructural studies have been carried out on these granules because of their infrequent presence in neutrophils. The bone marrow of 18 cases of chronic myeloproliferative disorders, including one case of chronic neutrophilic leukemia in which periodic lamellar granules were frequently seen in neutrophils, was investigated by electron microscopy. Periodic lamellar granules were seen in neutrophils in 12 of the 18 cases at varying frequencies. They were preferentially seen in immature neutrophils. The transverse profiles of these granules revealed concentric complete/incomplete rings or periodic parallel straight lines, i.e., various patterns of lamellar arrangement were present. Periodic lamellar granules were positive for myeloperoxidase and lysozyme at the electron-microscopic level. These results suggest that these granules represent a primary neutrophil granule subtype. However, their functional and pathologic significance remains unknown.