Information concerning the rate of bladder filling is determined by receptors in the bladder wall and conveyed via afferent fibers in the pelvic nerve to sensory neurons in the lumbosacral cord. It was assumed that this information is relayed from the lumbosacral cord to a medial cell group in the dorsolateral pontine tegmentum, called the M-region, the pontine micturition center, or Barrington's nucleus. The M-region, in turn, projects via long descending pathways to the sacral parasympathetic motoneurons. In the present electron microscopic study, it was investigated in cats whether monosynaptic projections from lumbosacral neurons to the M-region indeed exist. Wheat-germ agglutinin-horseradish peroxidase injections were made into the lumbosacral cord. Many retrogradely labeled dendrites and somata were found in the M-region, but no labeled terminals were found on retrogradely labeled dendrites or somata. Only a small number of anterogradely labeled terminals, which were filled with mainly round vesicles, contacted unlabeled dendrites in the M-region. In contrast, many more anterogradely labeled terminals, which were filled with mainly round and, to a limited extent, dense core vesicles and with asymmetrical synapses, were found on dendrites in the lateral part of the periaqueductal gray (PAG). Previously (Blok and Holstege [1994] Neurosci. Lett. 166:93-96), it was demonstrated that the lateral part of the PAG contains neurons projecting to the M-region. A concept for the central organization of the micturition reflex is presented in which ascending projections from the lumbosacral cord convey information on bladder filling to the PAG.(ABSTRACT TRUNCATED AT 250 WORDS)

SummaryTo develop an animal model for antimyeloperoxidase (MPO)-associated necrotizing crescentic glomerulonephritis (NCGN), we immunized Brown Norway rats with MPO and localized a neutrophil lysosomal enzyme extract, primarily consisting of MPO and elastinolytic enzymes, plus H202, the substrate of MPO, to the glomerular basement membrane (GBM). Upon immunization rats developed antibodies and positive skin tests to MPO. After unilateral perfusion of the left kidney with the lysosomal enzyme extract and H202, MPO and immunoglobulin (Ig)G localized transiently along the GMB. At the time of maximal inflammation, at 4 and 10 d after perfusion, MPO, IgG, and C3 could not be detected anymore. MPO-immunized rats perfused with the lysosomal enzyme extract and H202, in contrast to control-immunized and/or control-perfused rats, developed a proliferative GN characterized by intra-and extracapillary cell proliferation, ruptured Bowman's capsule, periglomerular granulomatous inflammation, and formation of giant cells. Monocytes, polymorphonuclear leukocytes (PMN), and to a far lesser extent T cells were found in the glomeruli. Interstitial infiltrates consisted of monocytes, PMN, and T cells. Granulomatous vasculitis of small vessels was found at 10 d after perfusion. The proliferative NCGN in this rat model closely resembles human anti-MPO-associated pauci-immune NCGN, and enables the study of the pathophysiology of anti-MPO-associated NCGN. N 'ecrotizing crescentic glomerulonephritis (NCGN), 1 a clinically rapidly progressive form of glomerular disease, can be associated with multisystem disorders (infectious or noninfectious), or may occur in patients without a definite diagnosis of systemic illness (1). NCGN can be classified into three immunopathogenic categories: (a) anti-glomerular basement membrane (GBM) antibody mediated; (b) immune complex mediated; and (c) antineutrophil cytoplasmic antibody (ANCA) associated (2). ANCA in patients with ANCAassociated NCGN are either directed to proteinase 3 (Pr3) (3-5) or myeloperoxidase (MPO) (2, 6, 7), both myeloid lysosomal enzymes. NCGN associated with anti-MPO antibodies is characterized by segmental fibrinoid necrosis of the GBM, marked infiltration of neutrophils and mononuclear cells, and paucity of IgG deposits (8-12). NCGN can be accompanied by granuloma formation (13,14). The pathogen-1 Abbreviations used in this paper: ANCA, antineutrophil cytoplasmic antibody; GBM, glomerular basement membrane; MPO, myeloperoxidase; NCGN, necrotizing crescentic glomerulonephritis; Pr3, proteinase 3. esis of ANCA-associated NCGN has not been elucidated so far. The close association between pauci-immune NCGN and anti-MPO antibodies (6, 7) suggests a pathogenetic role for an anti-MPO-directed immune response. In vitro studies showed that anti-MPO antibodies can activate PMN to cause a respiratory burst and to mediate degranulation (15). We hypothesized that NCGN may develop after focal release of lysosomal enzymes and production of H202 by activated neutrophils in the presence of an an...

No abstract

No abstract

No abstract