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)

Blood lysozyme estimation seems to be important in hematological practice. Serum levels are roughly proportional to the size of the pool and, above all, granulocytic renewal. Thus levels are increased compared with levels of circulating polynuclear cells. In bone marrow disorders, and particularly in myelofibrosis, owing to the infective granulopoiesis and/or increased destruction of the neutrophil polymorphs. It is lowered in neutropenia with a scanty bone marrow. It provides an important contribution to diagnosis of the type of acute leukemia, the fall in the lymphoblastic forms contrast with normal or increased levels in myeloblastic forms. Finally, there is a marked increase in lysosome urea in acute monocytic or myelomonocytic leukemia.
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PMID:[Lysozyme in hematologic diseases]. 16 45

Enzymaticaly homogeneous fractions of lymphocytes, monocytes, and neutrophils were isolated by zonal centrifugation from peripheral blood of a patient with hairy cell leukemia, or leukemic reticuloendotheliosis, LRE,(with leukopenia, neutropenia, lymphocytosis, and massive splenomegaly). To detect enzymatic deficiencies, the cells were analyzed quantitatively for six leukocytic enzymes on three occasions: 1) before splenectomy, 2) 5 days after splenectomy, and 3) 6 weeks after splenectomy. Before splenectomy, the patient's cells showed moderate deficiency of beta-glucuronidase in lymphocytes and monocytes; server to modorate deficiency of lysozyme and myeloperoxidase in monocytes and granulocytes; and complete absence of neutral protease and alkaline phosphates in neutrophils. Full restoration of neutral protease and a three-fold rise in alkaline phosphatase activities occurred in the patient's neutrophils 5 days after splenectomy. Lysozyme and myeloperoxidase returned to normal in both monocytes and neutrophils of the patient. Six weeks following splenectomy, the alkaline phosphatase activity again disappeared from patient's neutrophils, although neutral protease remained normal. The patient's lymphocytes were unresponsive to PHA and PW mitogen before splenectomy but became responsive 6 weeks postoperatively. Monocytic transfomation into macrophges was supressed before and after splenectomy. The findings indicate that developmenally, in lymphocytic leukemia, a biochemical defect involves the patient's monocytes and neutrophils much more severely than it affects the leukemic lymphocytes. Functionally, the results partly explain the susceptibility of LRE patients to microbial infections.
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PMID:Absence of neutral protease and alkaline phosphatase in neutrophils of a case of hairy cell leukemia. 43 13

Middle ear infection with Streptococcus pneumoniae is important in the pathogenesis of acute and chronic otitis media, and lysozyme in middle ear fluid (MEF) is an important inflammatory mediator in this disease. To determine the source of lysozyme during the early period of acute pneumococcal otitis media, chinchillas were irradiated to induce neutropenia, and their middle ears were inoculated with heat-killed, encapsulated pneumococci. The number of inflammatory cells and concentration of lysozyme were measured in MEF between 6 and 72 hours after inoculation. In pneumococcus-inoculated ears, the mean number of inflammatory cells but not lysozyme was significantly lower in MEF from irradiated animals than that from nonirradiated animals at 6 hours. Since lysozyme accumulated in MEF before the influx of inflammatory cells in irradiated animals, the initial release of this inflammatory mediator is most likely not from inflammatory cells; and mucosal epithelial cells, the only other known source of lysozyme in the middle ear environment, were the probable source induced by the direct stimulation of pneumococci. Inflammatory cells may contribute lysozyme later in the inflammatory response, since cellular and lysozyme concentrations in irradiated and nonirradiated animals were similar between 24 and 72 hours. These results suggest that future therapeutic interventions to limit middle ear inflammation in acute otitis media may need to recognize the direct action of pneumococcal cells or their envelope components on middle ear epithelium.
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PMID:Middle ear fluid lysozyme source in experimental pneumococcal otitis media. 206 74

Serum from a patient with inactive systemic lupus erythematosus (SLE) and ibuprofen-induced transient neutropenia was used as a probe to define further the control of human polymorphonuclear leukocyte (PMN) exocytosis and superoxide (O2-) generation. Thirty-minute preincubation of normal PMNs with 10-50% v/v of this serum, followed by washing, produced a specific dose-related suppression of leukotriene B4 (LTB4)-elicited beta-glucuronidase and lysozyme release of up to 45% and 30% respectively. If cells were not washed, the inhibition increased to 60% and 40%. Superoxide production stimulated by LTB4 was unaffected. The serum had no effect on formyl-met-leu-phe (FMLP) or phorbol myristate acetate-stimulated O2- or exocytosis. O2- and beta-glucuronidase release elicited by zymosan-treated serum (ZTS) were both decreased by 15%, but there was no increased inhibition seen if cells were not washed, or if the time of preincubation was increased from 7 to 30 min. In contradistinction, the serum inhibition of LTB4 exocytosis did show time dependence. Serum obtained when the patient was not leukopenic and sera from 6 normal controls, 2 patients with inactive SLE, 1 patient with SLE and chronic leukopenia, and 2 controls taking ibuprofen did not influence any PMN function. The serum inhibition of ZTS-induced functions was qualitatively similar to that observed when PMNs were preincubated and desensitized with ZTS in vitro. Selective inhibition of LTB4 exocytosis was not seen when PMNs were desensitized with LTB4 in vitro. These observations indicate that LTB4-elicited O2- and exocytosis can be independently and specifically regulated. The cellular site at which this serum factor acts is not clear, but the current studies strongly suggest that this inhibition is not due to in vitro deactivation by LTB4 activity.
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PMID:Independent regulation of leukotriene B4-elicited polymorphonuclear leukocyte exocytosis and superoxide generation by a serum factor. 303 8

Two chemoattractants, the peptide N-formyl-met-leu-phe (FMLP), and the ether phospholipid, platelet activating factor (PAF), each stimulate a variety of in vitro responses in polymorphonuclear leucocytes (PMN). Because often more than one inflammatory mediator is active during inflammation, we determined the effect on PMN of sequential stimulation with these two agents. Before FMLP stimulation, human PMN were exposed to PAF, at concentrations which gave little or no response when administered alone. PAF enhanced FMLP-elicited superoxide release in a dose-dependent fashion. Likewise, release of granular lysozyme from the cells was increased in PAF treated cells. Similar treatment with other phospholipids, including the lyso derivation of PAF, failed to produced these effects. Incubation with nordihydroguaiaretic acid, an inhibitor of arachidonic acid metabolism, had little effect on the enhancement of lysozyme release by PAF. To determine if enhancing effects by PAF might occur also in vivo, we studied rabbits receiving PAF and/or FMLP intravenously. When rabbits received 0.01 micrograms PAF (a dose which does not elicit the sustained neutropenia observed with higher doses of PAF) followed by 0.05 micrograms FMLP the absolute granulocyte count (AGC) dropped at 1 min (46 +/- 11% of original value), and continued to fall (24 +/- 12% at 10 min). Controls, treated with the suspending fluid for PAF, and then 0.05 micrograms FMLP, had a similar 1 min AGC value, but at 10 min AGC returned to 65 +/- 6.1% (P less than 0.001 for comparison of 10 min values). Thus PAF pretreatment enhanced FMLP-elicited granulocytopenia in vivo. Study of in vitro human PMN aggregation revealed that, at certain relative concentrations of PAF and FMLP, aggregation was enhanced. These studies show that both in vitro and in vivo responses of FMLP-stimulated PMN may be exaggerated by pre-exposure to PAF.
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PMID:In vitro and in vivo effects of treatment by platelet-activating factor on N-formyl-met-leu-phe-mediated responses of polymorphonuclear leucocytes. 303 60

High-dose immunoglobulin (HD-Ig) therapy was given to an infant with autoimmune neutropenia (AIN), and antineutrophil autoantibodies (ANAA). The patient's absolute neutrophil count in peripheral blood increased from 300/mm3 to 3000-4000/mm3 7 days after treatment. Although the neutrophil count gradually decreased thereafter, transient increases were observed after each single booster infusion repeated at 3-week intervals. By continuing this treatment, clinical symptoms were markedly alleviated, and the patient's susceptibility to infection was reduced. The increase in neutrophils showed a positive correlation with the increase in serum IgG, and with the increase in the ratio of the T helper/T suppressor cells. The neutrophil-bound IgG level and serum lysozyme level were decreased after HD-Ig therapy.
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PMID:Immunological and haematological changes during high-dose immunoglobulin therapy in an infant with autoimmune neutropenia. 365 38

Congenital dysgranulopietic neutropenia (CDN) is a recently proposed entity that describes a small subgroup of children with clinically severe neutropenia. We followed and studied a 3-year-old girl with neutropenia (less than 500/mm3) and recurrent severe infections in whom repeated marrow evaluations revealed large (30-50 microns) multinucleated promyelocytes to polymorphonuclear cells with as many as 4 to 16 nuclei or nuclear lobes, respectively. In addition to the nuclear endoreduplication, ultrastructural and cytochemical evaluation of these cells demonstrated abnormalities in granule genesis and centriole structure. Concomitantly, immunoperoxidase staining indicated that many of the granules were devoid of lactoferrin but not lysozyme. In vitro proliferation studies revealed normal to increased thymidine labeling, normal numbers of colony-forming cells, and normal colony-stimulating activity from blood and marrow mononuclear cells, findings consistent with ineffective myelopoiesis. However, serum folate, B12, and lysozyme levels were normal. The nuclear and cytoplasmic abnormalities in this patient result in an extreme example of CDN, distinct from previously described cases.
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PMID:Severe congenital neutropenia with unique features of dysgranulopoiesis. 396 63

The kinetics of blood neutrophils was investigated by means of the in vitro radioactive diisopropyl fluorophosphate method in 35 patients with a chronic, steady-state neutropenia. There were 17 patients in whom the half disappearance time of neutrophils was normal. In 10 of these patients, the production of neutrophils was low and in 7, production was normal. In 18 patients the half disappearance time of neutrophilic granulocytes was shorter than normal. The production of neutrophilic granulocytes was low in five of these patients, normal in eight patients, and increased in five. An attempt was made to correlate other laboratory measurements with the kinetic picture, but no relationship was found; the marrow neutrophil reserve as measured by endotoxin or cortisol injection; marrow cellularity on aspiration or biopsy; in vitro-labeling index with (3)HTdR; or serum lysozyme concentration proved of no value in identifying the various kinetic groups. The only finding that seemed to correlate with the kinetic picture was the presence or absence of splenomegaly. In 12 of the 18 patients with a short half disappearance time, splenomegaly was present whereas in 15 of 17 patients with a normal half disappearance time, there was no splenomegaly. Of 20 patients with greater than 1000 neutrophils per mm(3), 17 were found to have a normal total-blood neutrophil pool. Thus these patients, with many of their cells marginated, agree to have a "shift neutropenia."Myelocyte to blood transit time and myelocyte generation time, as measured in seven patients by in vivo labeling with diisopropy fluorophosphate, proved to be essentially normal. Thus, it appears that in chronic neutropenia, increased or decreased production of neutrophils is accomplished by increasing or decreasing early precursor input into the system.
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PMID:Leukokinetic studies. XIV. Blood neutrophil kinetics in chronic, steady-state neutropenia. 509 74

Intravenous gammaglobulin (IVIgG) was used to treat autoimmune neutropenia of infancy in two males with repeated infections. The neutrophil count increased significantly in both patients with the initial IVIgG therapy; 1 patient went into remission. The neutrophil count in the other remained above baseline for 3 wk, and a subsequent booster infusion also caused the neutrophil count to increase. The patients have remained clinically well since their treatment began. Serial studies of antineutrophil antibody and serum lysozyme, performed to elucidate the mechanism of action, suggested decreased neutrophil destruction, perhaps by Fc receptor blockade, as well as decreased synthesis of antineutrophil antibody. Neutrophil function was not impaired after the neutrophil count increased. Many patients with immune neutropenia have a benign course, but those who have significant infections could be treated, acutely or prophylactically, with intravenous gammaglobulin.
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PMID:Reversal of neutropenia with intravenous gammaglobulin in autoimmune neutropenia of infancy. 619

The anti-inflammatory effects of gold compounds include suppression of PMN lysosomal enzyme release. Since lysosomal products can provoke PMN aggregation, we assessed the effect of two gold compounds, auranofin and GST, on suppressing aggregation, degranulation, and metabolic functions of the cells. Aggregation of 1 x 10(7) cytochalasin B-treated PMNs in response to 2 x 10(-7)M FMLP, as assessed by light scattering, was inhibited in a dose-dependent fashion by both drugs. Concentrations of auranofin ranging from 5 to 20 microM caused 30.8% to 89% inhibition, whereas 200 microM GST reduced aggregation by only 32%. FCS or BSA added to suspensions of normal PMNs considerably reduced the gold compound inhibitory effect on PMN aggregation. Cell viability assessed by dye exclusion and lactate dehydrogenase release was unaffected by the drugs. The suppressive activities of the drugs could not be removed by washing the PMNs. Correspondingly, the drugs suppressed lysosomal enzyme release induced by FMLP of PMNs rendered secretory with cytochalasin B. Concentrations of 20 microM auranofin and 200 microM GST resulted, respectively, in a 61.5% and 19.3% reduction of release of lysozyme, 61.7% and 27.1% reduction of beta-glucuronidase, 84.8% and 33.7%s reduction of myeloperoxidase, and 50.0% and 25.0% reduction of lactoferrin. Furthermore, auranofin inhibited 14C-1-glucose oxidation through the hexose monophosphate shunt in response to stimulation by either PMA or methylene blue. The in vivo studies suggested that auranofin could prevent neither neutropenia induced by zymosan-activated serum nor a corresponding rise in plasma lactoferrin levels. These findings suggest that the beneficial effect of gold compounds in rheumatoid arthritis are unlikely to be related to their ability to dampen PMN activation in vivo.
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PMID:Correlation of in vitro and in vivo effects of gold compounds on leukocyte function: possible mechanisms of action. 628 1


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