Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cyclic neutropenia (CN) is an inherited disease known to occur in both humans and Gray Collie dogs. In dogs, the disease is characterized by a profound and cyclic decrease in circulating granulocytes at 12-day intervals. Other formed elements of the blood also show cyclic changes and thus the disease is also called cyclic hematopoiesis (CH). In this study, daily serum levels of lysozyme and a factor with macrophage migration inhibitory (MIF) activity were assayed. Both MIF activity and lysozyme levels were elevated more than 2-fold and fluctuated cyclically in CH dogs during the 12-day cycle: CH dogs CH 490 and CH 491, had 32.7 +/- 16.8% and 35.9 +/- 18.3% migration inhibitory activity, respectively, as compared to 15.1 +/- 1.4% in normal dog N 492; CH 490 and CH 491 had 78.7 +/- 43.7 units and 86.9 +/- 58.7 units of lysozyme, respectively, as compared to 33.4 +/- 1.7 units in N 492. The change of MIF activity tended to precede that of lysozyme activity in CH dogs. Furthermore, MIF levels and monocyte counts correlated significantly during the 12-day neutropenia cycle (CH 490, r = 0.677, P less than 0.001; CH 491, r = 0.583, P less than 0.01).
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PMID:Increase in the serum macrophage migration inhibitory activity and lysozyme in dogs affected with cyclic hematopoiesis. 675 48

Neutropenia and/or leukopenia (associated with elevated serum lysozyme levels) in three children with vitamin B12 deficiency were evaluated using soft agar culture and ultrastructural and cytochemical techniques. In two patients a marked increase in peripheral myeloid colony forming cells (CFC) was observed; whereas a marginal increase in CFC was present in the third, less symptomatic, patient. Marrow CFC was normal or slightly increased. Serum colony stimulating activity (CSA) was normal but elaboration of CSA by white blood cells was low. Normal maturation of the progenitors was present in vitro and serum inhibitors of myelopoiesis were absent. Megaloblastic neutrophils and monocytes with nuclear-cytoplasmic asynchrony were observed ultrastructurally in directly sampled marrow specimens. These cells contained autophagic and/or heterophagic vacuoles and an increase in cytoplasmic granules. Both monocytes and neutrophils also contained enlarged-disrupted centrioles. Many marrow macrophages contained phagocytic vacuoles, which enclosed disrupted neutrophils and cellular debris.
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PMID:Dysgranulopoietic neutropenia and abnormal monocytes in childhood vitamin B12 deficiency. 696 26

Rabbit granulocyte lactoferrin, when infused into hamsters or rabbits, induces transient neutropenia, and in hamsters the lactoferrin promotes adherence of the granulocytes to the endothelial cell wall as monitored visually. In contrast, neither rabbit granule lysozyme nor human transferrin induces neutropenia in the rabbit nor does transferrin or bovine serum albumin affect the adherent properties in vivo of the phagocytic cells of the hamster. Thus lactoferrin enhances granulocyte adherence both in vivo and in vitro. It would appear that the promotion of margination of leukocytes by lactoferrin in vivo may contribute to the phenomenon of neutropenia during activation of granulocytes by chemotactic factors.
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PMID:Neutropenia induced by systemic infusion of lactoferrin. 707 27

Six children with severe congenital neutropenia and repeated life-threatening infections were investigated by examining clinical features and myeloid cell ultrastructure, cytochemistry, and in vitro proliferation. Despite the presence of neutropenia, normal numbers of colony-forming cells (CFC) were present in blood and marrow specimens, and colony-stimulating activities (CSA) from blood cells and serum were normal or slightly increased in all patients. In vitro maturation of the progenitors to neutrophils was also uniformly present in the colonies. No patients had demonstrable antineutrophil antibodies or serum inhibitors of myelopoiesis. Serum lysozyme levels were normal. Ultrastructural and cytochemical studies of directly sampled marrow cells revealed several abnormalities in most neutrophilic myeloid cells from each of the patients consistent with an intrinsic myeloid precursor cell defect. These included (1) the defective synthesis or degeneration of primary granules, (2) an absence or marked decrease of secondary granules in the few late neutrophils observed in the bone marrow, and (3) the presence of autophagy. Phagocytosis of intact myeloid cells with subsequent degeneration was not observed; however, neutrophil debris was evident in phagocytic vacuoles of marrow macrophages. Our demonstration of ultrastructurally dysmorphic neutrophilic granulocytes, intramedullary cell lysis, normal stem cell numbers, and negative serology is comparable to similar observations of erythroid cells from patients with congenital dyserythropoietic anemia. We therefore hypothesize that the dysgranulopoiesis in these children results in neutropenia and propose the descriptive name congenital dysgranulopoietic neutropenia.
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PMID:Congenital dysgranulopoietic neutropenia: clinical, serologic, ultrastructural, and in vitro proliferative characteristics. 740 13

Novel recombinant human C5a receptor antagonists were discovered through modification of the C terminus of C5a. The C5a1-71T1M,C27S,Q71C monomer, (C5aRAM; CGS 27913), was a pure and potent functional antagonist. The importance of a C-terminal cysteine at position 71 to antagonist properties of C5aRAM was confirmed by studying C5a1-71 derivatives with replacements of Q71, C5a derivatives of various lengths (70-74) with C-terminal cysteines, and C5a derivatives of various lengths (71-74) with Q71C replacements. The majority of C5a1-71Q71 derivatives were agonists (C5a-like) in the human neutrophil C5a-induced intracellular calcium mobilization assay. The C5a1-71Q71C derivative was an antagonist. C5a derivatives of lengths 73 and 74 with C-terminal cysteines were agonists, while lengths 70 to 72 were antagonists. C5a derivatives of lengths 72, 73, and 74 with Q71C replacements were agonists, while, again, C5a1-71Q71C was an antagonist. C5aRAM and its adducts, including its dimer, C5aRAD (CGS 32359), were pure antagonists. Additionally, CSaRAM and CSaRAD inhibited binding of 125I-labeled recombinant human C5a to neutrophil membranes (Ki = 79 and 2 pM, respectively), C5a-stimulated neutrophil intracellular calcium mobilization (8 and 13 nM), CD11b integrin up-regulation (10 and 1 nM), superoxide generation (182 and 282 nM), lysozyme release (1 and 2 microM), and chemotaxis (11 and 7 microM). In vivo, intradermal injection of C5aRAM inhibited C5a-induced dermal edema in rabbits. Furthermore, a 5-mg/kg i.v. bolus of C5aRAD significantly inhibited C5a-induced neutropenia in micropigs when challenged with C5a 30 min after C5aRAD administration. C5aRAM and C5aRAD are novel, potent C5a receptor antagonists devoid of agonist or proinflammatory activity with demonstrated efficacy in vitro and in vivo.
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PMID:Novel C5a receptor antagonists regulate neutrophil functions in vitro and in vivo. 960 67

Serum concentrations of hepatocyte growth factor (HGF) were measured in 60 patients suffering from acute myelocytic leukaemia (AML). At the time of diagnosis elevated HGF concentrations (> 1.25 ng/ml) were found in 28% of the patients. HGF levels correlated with the presence of disseminated intravascular coagulation (DIC), levels of lysozyme, creatinine, peripheral blood blast counts and lactic dehydrogenase. In the group of patients with high HGF (>1.25 ng/ml) we found a tendency towards an increased early mortality; 41% of them died within 15 d from diagnosis, as opposed to 5% of the patients with normal HGF (log rank test p=0.07). DIC-related bleeding or thrombosis contributed to this early mortality. In responders, HGF levels normalized after treatment. HGF levels are low in neutropenia and neutropenic infections.
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PMID:Elevated serum concentrations of hepatocyte growth factor in acute myelocytic leukaemia. 1005 17

Severe sepsis is one of the leading causes of death worldwide. High mortality rates in sepsis are frequently associated with neutropenia. Despite the central role of neutrophils in innate immunity, the mechanisms causing neutropenia during sepsis remain elusive. Here, we show that neutropenia is caused in part by apoptosis and is sustained by a block of hematopoietic stem cell (HSC) differentiation. Using a sepsis murine model, we found that the human opportunistic bacterial pathogen Pseudomonas aeruginosa caused neutrophil depletion and expansion of the HSC pool in the bone marrow. "Septic" HSCs were significantly impaired in competitive repopulation assays and defective in generating common myeloid progenitors and granulocyte-monocyte progenitors, resulting in lower rates of myeloid differentiation in vitro and in vivo. Delayed myeloid-neutrophil differentiation was further mapped using a lysozyme-green fluorescent protein (GFP) reporter mouse. Pseudomonas's lipopolysaccharide was necessary and sufficient to induce myelosuppresion and required intact TLR4 signaling. Our results establish a previously unrecognized link between HSC regulation and host response in severe sepsis and demonstrate a novel role for TLR4.
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PMID:Dysfunctional expansion of hematopoietic stem cells and block of myeloid differentiation in lethal sepsis. 1969 1


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