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

Neutropenia was produced in goats by injection of either nitrogen mustard, (1.5 mg/kg) or hydroxyurea (200 mg X kg-1 X day-1). A nitrogen mustard (M + E) group (n = 6), a hydroxyurea (H + E) group (n = 5), and a control (E) group (n = 7) were given 1-h infusions of endotoxin (5 micrograms/kg total dose), then monitored for up to 5 h. Postmortem extravascular lung water (EVLW) was significantly higher in the M + E group (14.2 +/- 4.4 ml/kg) and the E group (11.9 +/- 3.9 ml/kg) when compared with a normal control (6.6 +/- 1.3 ml/kg) group that did not receive endotoxin. EVLW in a group made neutropenic with nitrogen mustard (6.7 +/- 1.3 ml/kg) and the H + E (7.9 +/- 1.5 ml/kg) groups were not statistically different from each other or from normal controls. Circulating neutrophil counts averaged 32 +/- 42 cells/microliter in the M + E group and 180 +/- 210 cells/microliter in the H + E group. Only minimal histological changes were seen in the H + E group, but the E and M + E lungs had severe pulmonary edema. We conclude that neutrophils are not required for increased EVLW and decreased arterial O2 partial pressure after endotoxin infusion, and hydroxyurea prevents at least part of the pulmonary edema after endotoxin by a mechanism that is not neutrophil dependent.
 ...
PMID:Neutrophil depletion does not prevent lung edema after endotoxin infusion in goats. 354 69

Intravascular complement activation induces a rapid neutropenia and transient hypotension in laboratory animals such as rabbits. Injection of purified C5a causes similar hemodynamic events, and the hematologic changes suggest involvement of components such as polymorphonuclear leukocyte (PMN) and mediators including vasoamines and prostanoids. The anaphylatoxin-induced hypotension coincided with an increase in central venous pressure (CVP), decreased cardiac output (CO), increased plasma prostanoid levels, and neutropenia. These phenomena were repeatable in the animals when C5a was administered as a bolus 45 min after the initial treatment. Animals pretreated with indomethacin failed to exhibit the hypotensive response to C5a but still exhibited the transient neutropenia. Indomethacin effectively eliminated prostanoid release into plasma as expected. Administration of H2, but not H1, histamine-receptor antagonists reduced both C5a-induced hypotension and prostanoid release, suggesting that histamine may contribute to the C5a response in rabbits. Animals rendered neutropenic with nitrogen mustard prior to C5a challenge respond normally to C5a infusion (i.e., elevated prostanoid release and hypotension). The mechanism that we proposed for C5a-induced hypotension requires vascular smooth muscle contraction to be predominant over peripheral vasodilation in affecting cardiac output. Neutropenia occurs as a parallel event to hypotension but seemingly has little influence on the hemodynamic response. Prostacyclin (PGI2) levels were elevated in C5a-treated animals, and this lipid mediator contributes to hypotension by enhancing peripheral vasodilation. Because plasma TGxB2, levels were also elevated and central venous pressure increased as cardiac output decreased in treatment animals, we concluded that thromboxane-dependent pulmonary vasoconstriction contributes significantly to the C5a hypotensive response.
 ...
PMID:Complement activation and membrane lipids in lung vascular injury. 361 9

1 The mechanisms by which agents modulate the induction of kinin B1-receptors were investigated by studying the effects of kinins in vitro, by use of the rabbit isolated aorta, and in vivo by measuring the blood pressure of anaesthetized rabbits. 2 The contractile response of the rabbit isolated aorta to kinins increased in a time-dependent manner in vitro. This effect was abolished by continuous exposure to the protein synthesis inhibitor cycloheximide (71 microM). 3 Several substances were found to increase specifically the rate of sensitization to des-Arg9-bradykinin (des-Arg9-Bk), when applied continuously in vitro to tissues isolated from normal animals: bacterial lipopolysaccharide (LPS; 1 micrograms ml-1), muramyl-dipeptide (MDP; 2 micrograms ml-1), phorbol myristate acetate (PMA; 320 nM), epidermal growth factor (EGF; 100 ng ml-1) and endothelial cell growth factor (150 micrograms ml-1). 4 The protease inhibitors phenylmethylsulphonyl fluoride and aprotinin, a non-adjuvant isomer of MDP, rabbit purified leukocyte interferon, fibroblast growth factor and the chemotactic peptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) did not have this effect. 5. It has been demonstrated that LPS induces B1-receptors in rabbits enabling des-Arg9-Bk to act as a hypotensive agent. In these experiments neutropenia induced by nitrogen mustard, did not prevent the in vivo effect of LPS. MDP (300 micrograms) and PMA (100 micrograms) were also found to induce a state of responsiveness to des-Arg9-Bk in vivo. FMLP (1 mg i.v.) induced a temporary decrease in blood neutrophil counts but had no effect on the induction of responses to des-Arg9-Bk. 6. The development of responses mediated by the B,-receptor in the two experimental systems seems to be unrelated to the activation of neutrophil leukocytes, but may be related to the activation of tissue macrophages. Approximately 3% of cultured adherent cells derived from rabbit aorta strips following protease digestion were stained for non-specific esterase, supporting such a possibility.
 ...
PMID:Studies on the induction of pharmacological responses to des-Arg9-bradykinin in vitro and in vivo. 367 93

Three adolescent patients with severe seizure disorders were treated with phenacemide. All three patients showed elevated serum creatinine and normal blood urea nitrogen values while on phenacemide. Simultaneous urea and creatinine clearance studies performed on each patient demonstrated normal urea clearances and decreased creatinine clearances. Inulin clearance performed in one patient was normal. The medication was discontinued in two of the patients because of co-existing neutropenia. Serum creatinine values returned to normal after phenacemide treatment was terminated. The elevation in serum creatinine values with phenacemide appears to be dose related, reversible, and unrelated to impairment of glomerular filtration.
 ...
PMID:Elevated serum creatinine levels in three patients treated with phenacemide. 395 82

We did two studies to see if severe neutropenia might reduce the severity or delay development of O2-induced lung microvascular injury. First, we treated 11 rabbits with nitrogen mustard until their circulating neurophil count decreased to less than 50/microliters of blood, after which the rabbits breathed pure O2 until death; nine other rabbits received no nitrogen mustard and had normal numbers of circulating neutrophils during O2 breathing. All rabbits died of respiratory failure with pulmonary edema, and although chemotherapy decreased the number of neutrophils in the lungs by greater than 90%, it did not influence survival time or extravascular lung water content. To see if severe neutropenia might slow the development of O2-induced lung microvascular injury, we assessed the effects of sustained hyperoxia on lung fluid balance in unanesthetized lambs treated with hydroxyurea, so that their absolute neutrophil count was less than 50/microliters of blood. We measured pulmonary arterial and left atrial pressures, cardiac output, lung lymph flow, and concentrations of protein in lymph and plasma during a 2- to 4-h control period and then daily for 2 to 4 h as the lambs continuously breathed pure O2. After 3 days of hyperoxia, lymph flow doubled and the concentration of protein in lymph increased from 3.3 +/- 0.5 to 4.2 +/- 0.3 g/dl. Tracer studies with 125I-albumin before and 3 days after the start of O2 breathing confirmed the development of increased lung vascular permeability to protein. All lambs died of respiratory failure with pulmonary edema after 3-5 days in O2.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Oxygen-induced lung microvascular injury in neutropenic rabbits and lambs. 398 Mar 93

Platelets can release a variety of inflammatory mediators. These formed elements have been shown to accumulate early in acute inflammation, often prior to fibrin and thrombus formation. Polymorphonuclear leukocyte (PMNL) infiltration is also an early event and is linked to protein exudation and hyperemia. The relationship between PMNL and platelet accumulation was studied. Inflammation was induced in rabbits by intradermal injection of stimuli, and 51Cr-labeled leukocytes and 111In-labeled platelets were used to quantitate the rates of leukocyte and platelet accumulation in the dermal reactions. A temporal association between the rates of leukocyte infiltration (greater than 95% PMNL) and of platelet deposition at skin sites was observed when killed Escherichia coli, E. coli-derived chemotactic factors, zymosan-activated plasma, f-met-leu-phe, or endotoxin were injected intradermally. A linear correlation (r = 0.96; p less than 0.001) between these parameters was observed. 59Fe-labeled red cells did not accumulate in these lesions. Platelet deposition in response to inflammatory stimuli did not occur in PMNL-depleted (nitrogen mustard treatment) but platelet-sufficient rabbits, in spite of normal platelet deposition in thrombin-injected sites. Platelet responses to inflammatory stimuli were normal when neutropenia, after nitrogen mustard treatment, was prevented. In contrast, in situ PMNL reconstitution of the skin sites in neutropenic rabbits did not cause local platelet accumulation. Intravenous infusion of the synthetic chemotactic factor, f-met-leu-phe, induced transient neutropenia and thrombocytopenia (30% of control) with platelet sequestration primarily in the lung. This is also the known site of PMNL sequestration during f-met-leu-phe infusion. It is concluded that platelets selectively deposit in acutely inflamed tissues primarily during PMNL margination in, and emigration across, the microvasculature. Platelets and PMNLs likely coassociate on the vessel wall, and this interaction may influence the course of inflammation.
 ...
PMID:Role of neutrophils in the deposition of platelets during acute inflammation. 636 76

The induction of neutropenia and immunosuppression by the administration of nitrogen mustard (HN2) decreased the frequency and altered the morphology of clinically detectable hematogenous Candida endophthalmitis in the rabbit model of disseminated candidiasis. Whereas 95% of eyes in rabbits infected with Candida albicans without pretreatment with HN2 developed typical lesions of hematogenous Candida endophthalmitis, only 6.2% of eyes in rabbits that had been given 3.0 mg of HN2 per kg developed clinically detectable endophthalmitis. Lesions that developed in the severely immunocompromised and neutropenic rabbits were small and atypical in appearance. From these data, we conclude that ophthalmoscopic examination may not be a sensitive diagnostic modality for disseminated candidiasis in severely immunocompromised, neutropenic patients.
 ...
PMID:Effect of immunosuppression on the development of experimental hematogenous Candida endophthalmitis. 696 12

We have previously shown a marked difference in the inflammatory response to human C5a or C5a des arginine (Arg) instilled in rabbit lungs. These studies raised the question of where C5a and C5a des Arg are processes in vivo and what role neutrophils may play in the tissue distribution of these two mediators. After intravenous injection of purified, biologically active 125I-C5a or 125I-C5a des Arg, adult rabbits were serially bled and then killed at various time intervals. Although greater than 50% of the injected radioactivity was cleared from the circulation within 2 min for both mediators, C5a des Arg persisted in the circulation longer than C5a. C5a instillation caused an acute neutropenia, whereas C5a des Arg caused a less severe and more prolonged neutropenia, preceding a neutrophilic response observed with both mediators. Clearance of the mediators was primarily seen in the highly vascularized organs: the lung, spleen, liver, and kidney. A time-dependent accumulation was seen initially in the lung, followed by the spleen, liver, and kidney. Histologic examination showed a marked increase in the number of neutrophils within the lung and spleen. Depletion of circulating neutrophils by nitrogen mustard pretreatment of rabbits showed no change in the amount of labeled mediator bound in the lung, whereas splenic accumulation was dependent on the presence of neutrophils. These results indicate that C5a and C5a des Arg are rapidly removed from the circulation by specific accumulation in vascularized tissues. Clearance by the lung was not affected by neutrophil depletion, whereas clearance by the spleen was dependent on neutrophils. These experiments further suggest there are neutrophil-dependent and neutrophil-independent mechanisms involved in the removal of C5a and C5a des Arg from the circulation and that binding of C5 fragments in the pulmonary vasculature may precede and then induce neutrophil sequestration.
 ...
PMID:In vivo clearance and tissue distribution of C5a and C5a des arginine complement fragments in rabbits. 717 88

In May 1991, clinical, pathologic, and virologic investigations were carried out on an 8-yr-old male lion (Panthera leo), with recurrent infections, in captivity with two lionesses in the Zoological Garden of Pistoia, Tuscany, Italy. The lion had severe pneumonia, neutropenia, thrombocytopenia, and an increase in blood urea nitrogen and creatininemia; in spite of therapy, it died within 3 months. At necropsy, the animal had a lymphoma and other lesions similar to those described in feline immunodeficiency virus-infected cats. We identified FIV gag-sequence using PCR amplification of lymph node tissues.
 ...
PMID:Lentivirus infection in an African lion: a clinical, pathologic and virologic study. 756 28

The authors describe the development of a clinical protocol to treat mustard gas-induced myelosuppression with granulocyte colony stimulating factor (G-CSF), a hematopoietic growth factor. Limited clinical evidence suggests a significant role for mustard gas-induced myelosuppression in the overall morbidity of mustard gas victims. Initial data from primates revealed that G-CSF could ameliorate neutropenia following nitrogen mustard exposure. Exploiting the extensive oncologic experience with G-CSF, which demonstrated its safety and absence of serious side effects the authors developed a clinical protocol for use of this drug in potential mustard gas victims in the Persian Gulf conflict.
 ...
PMID:Granulocyte colony stimulating factor (G-CSF) for mustard-induced bone marrow suppression. 768 84


<< Previous 1 2 3 4 5 Next >>