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)

The mechanism of neutropenia in Felty's Syndrome (FS) was tested. The suppressor capacity of mononuclear cells from patients with FS on normal bone marrow granulopoiesis was tested by the in vitro colony forming unit in culture assay. Peripheral blood, bone marrow, and spleen cells from FS patients with marked neutropenia (less than 1,000 neutrophils/mm3) suppressed the colony forming unit in culture of normal bone marrow. Cells from rheumatoid arthritis patients without neutropenia, cells from patients with drug-induced neutropenia without rheumatoid arthritis, or plasma from FS patients failed to suppress the colony forming unit in culture. Though suppressor cells were predominantly thymus-derived (T) cells, monocytes were also effective in suppression. The suppressor efficiency of cells from the various compartments were spleen greater than bone marrow greater than peripheral blood. Splenectomy in FS transiently corrected the neutropenia and eliminated suppressor cell activity. Hyperactive suppressor cells may be responsible for the neutropenia in some patients with FS. Correction of neutropenia in these patients should be directed at modulating the suppressor cell subpopulation.
 ...
PMID:Suppressor cell-mediated neutropenia in Felty's syndrome. 30 25

A man with polymyalgia rheumatica (patient 1) and two patients (2 and 3) with Felty's syndrome had neutropenia at the time of diagnosis. Bone marrow samples in each patient were cellular but showed an "arrest" of granulocyte maturation at the myelocyte stage. Agar colony growth of marrow cells from each patient was subnormal but increased after removal of sheep erythrocytes rosette-forming cells (thymus-dependent [T] cells) from marrow cell suspensions before culture. Preincubation of marrow cells with cortisol also enhanced colony growth. Maximum enhancement with cortisol occurred at 1 mM (patient 1), 1 microM (patient 2), and 10 nM (patient 3). Cortisol failed to enhance colony growth after removal of T cells from marrow cell suspensions. Peripheral blood lymphocytes (PBL) and PBL-conditioned medium from all three patients inhibited colony growth of normal human marrow cells. Cortisol treatment of PBL or T depletion from PBL abrogated the inhibition in coculture and with conditioned medium. Prednisone therapy resulted in the disappearance of suppressor T-cell function concomitant with hematologic improvement in patients 2 and 3, but suppressor T cells persisted in patient 1, who did not respond to prednisone. We conclude that cortisol-sensitive T lymphocytes inhibited granulopoiesis in vitro probably by elaboration of a soluble factor or factors. Our results suggest (a) that neutropenia in these patients resulted, at least in part, from T-cell suppression of granulopoiesis, (b) that the effectiveness of prednisone therapy was a result of its inhibition of suppressor T cells, and (c) that responses to glucocorticoid therapy may be predicted in such patients with the agar culture technique and cortisol dose response in vitro.
 ...
PMID:Neutropenia in three patients with rheumatic disorders. Suppression of granulopoiesis by control-sensitive thymus-dependent lymphocytes. 31 12

Coventional kittens, 12-27 weeks old, were inoculated with cell-cultured feline panleucopenia virus and killed sequentially between day 3 and day 24 after inoculation. All developed a non-fatal mild disease between days 2 and 9, characterized by lymphopenia, neutropenia, listlessness, depression and the development of neutralizing antibodies to the virus. Small intestinal bacterial counts were reduced during the period of maximal clinical disease, presumably a result of decreased food intake. There was involution of the thymus with marked depletion of lymphocytes between days 3 and 12. Depletion of lymphocytes also characterized the lesions in the lymph nodes between days 3 and 8. At the same time crypt lesions with spotty distribution were in the small intestinal and colonic mucosa. The changes were loss of crypt epithelial cells with compensatory attenuation of the remaining epithelium. Electron microscopically, the number and size of microvilli and secretory granules were reduced but there was no change indicating lethal cell injury. There were no virus particles. The findings point to an early and transient cellular damage by the virus. Intestinal alkaline phosphatase activity disappeared from the luminal surface of the attenuated crypt epithelial cells. Otherwise, intestinal alkaline and acid phosphatase activity were not altered in inoculated cats.
 ...
PMID:Experimental feline panleucopenia in the conventional cat. 93 27

We performed clinicopathological studies on early-onset sepsis (5 infants, less than 72 hours of life, EOS) and late-onset sepsis (15 infants, greater than 72 hours, LOS) of very low birth weight, less than 1500 g (VLBW). In EOS, the clinical features mimic the respiratory distress syndrome and hematological changes were not observed. The lungs showed slight interstitial pneumonia with structural immaturity, hyaline membranes, hemorrhage, and minimal infiltration by polymorphonuclear neutrophils (PMNs). The pathogen was group B streptococcus or weakly gram-negative bacilli. In LOS, pneumonia proceeded to sepsis and neutropenia with elevated numbers of circulating immature neutrophils, and increased levels of C-reactive protein were observed at the onset of sepsis. Severe pneumonia with infiltration of numerous PMNs and bacterial colonies and polymicrobial infection by nosocomial pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa were common. The thymus and spleen weights varied but retained normal structure in EOS. The thymus was depleted of lymphocytes, and the spleen was hypertrophic but poorly reactive against infection in LOS. The pathogenesis of EOS is regarded as being more closely correlated with lung immaturity and circulatory disorder in early life, whereas that of LOS is associated with immunological defenses of the host, potency of the pathogens, and terminal multiple organ failure.
 ...
PMID:Clinicopathological differences between early-onset and late-onset sepsis and pneumonia in very low birth weight infants. 223 61

A boy with combined immunodeficiency having low natural killer (NK)-cell activity received thymopoietin pentapeptide (TP-5) treatment, transplanted with T cell-depleted HLA-haploidentical bone marrow (BMT) cells from his father and with thymus tissue from an infant at different times during the first year of life. He showed a marked increase in large granular lymphocytes (LGL) both during the treatment with TP-5 and after BMT. The LGL generated following TP-5 injection had a T3+Leu11- surface phenotype and low NK activity. In contrast, the LGL appearing after BMT showed T3-, Leu7+, and/or Leu11+ surface phenotypes, had high NK- and K-cell activities, and were lymphokine-activated killer (LAK)-cell precursors. These killer activities were assigned to the Leu7-Leu11+ subset and proved to be of recipient origin. LGL proliferation following BMT was accompanied by neutropenia, which was improved in association with a reduction in the number of LGL and the appearance of T cells of BMT donor origin following thymus transplantation. This suggested the inhibition of granulopoiesis by the LGL and an in vitro study revealed that the Leu7+Leu11- subset of LGL suppressed the growth of granulocyte/macrophage colony-forming units. These results indicated that phenotypically different LGL could be generated by different treatments and that the LGL showing NK activity were distinct from those regulating granulopoiesis. It was also suggested that the generation of LGL was controlled by T cells.
 ...
PMID:Phenotypical and functional heterogeneity of the large granular lymphocytes increased after various treatments in a patient with combined immunodeficiency. 264 8

Cyclic hematopoiesis (CH), also called cyclic neutropenia, is an inherited disorder known to occur in both humans and gray collie dogs. Previous reports have provided ample evidence to suggest that lymphocyte activity and regulatory mechanisms may be abnormal in CH. The present study examined the lymphocyte populations of several lymphoid compartments of gray collie dogs. The percentage of B lymphocytes in the lymph nodes of CH dogs was significantly increased whereas that of null lymphocytes was decreased. The percentage of T lymphocytes did not differ between CH and normal dogs, however, the proportions of T lymphocyte subpopulations were significantly different. The levels of T lymphocytes expressing IgGFc receptors (T gamma) in the thymus, lymph nodes, and peripheral blood were significantly increased; whereas the levels of T lymphocytes expressing IgMFc receptors (T mu) were significantly decreased. The percentage and absolute numbers of T gamma and T mu lymphocytes cycled in CH dogs. The percentage and absolute numbers of neutrophils were greatest when that of T gamma lymphocytes was reduced. The cycles of monocytes and T gamma lymphocytes occurred in close association and a linear relationship between the levels of these cells was observed both in terms of percentage (r = 0.62; P less than 0.01) and absolute number (r = 0.67; P less than 0.05). The percentage of T gamma and T mu lymphocytes were inversely correlated (r = -0.68; P less than 0.01).
 ...
PMID:Canine cyclic hematopoiesis: alterations in T lymphocyte subpopulations in peripheral blood, lymph nodes, and thymus of gray collie dogs. 294 80

Antilymphocyte globulin is an immunoglobulin preparation prepared from heterologous serum after the animal (horse or rabbit) has been immunised with human lymphocytes, obtained from the thymus (antithymocyte globulin, ATG) or thoracic duct (antilymphocyte globulin, ALG). The rationale for the use of ALG in the treatment of chronic acquired marrow failure is based on its immunosuppressive activity and the fact that a proportion of cases of bone marrow failure, whether affecting single or multiple haemopoietic cell lines are due to immune-mediated suppression of haemopoiesis. In addition, in vitro studies have shown that ALG also has an immunostimulatory effect on lymphokine and haemopoietic growth factor production, and may therefore directly stimulate haemopoietic progenitor cells. ALG has been used for the treatment of aplastic anaemia and acquired chronic marrow failure affecting single cell lines namely pure red cell aplasia (PRCA), amegakaryocytic thrombocytopenia and chronic neutropenia due to immune inhibition of granulopoiesis ('acquired white cell aplasia'). ALG is used for treatment of non-severe aplastic anaemia (NSAA) and in those cases of severe aplastic anaemia (SAA) where allogeneic transplantation is not possible or is not indicated. Treatment with ALG results in 75% long term survival for NSAA and 40-50% for SAA although there is a very severe subgroup of SAA defined by peripheral blood neutrophils of less than 0.2 x 10(9)/l who rarely benefit from ALG therapy. For those patients who do not respond a second course of ALG can be given later using ALG from a different animal source.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:The role of antilymphocyte globulin in the treatment of chronic acquired bone marrow failure. 305 59

Sixteen adolescent specific pathogen free cats were inoculated with the Petaluma strain of feline immunodeficiency virus (FIV) and two cats were then necropsied at each of 5, 10, 21, 28, 42, 56, 70, and 84 day time points following infection. Lymphadenopathy gradually increased starting at Day 10 and persisted for the duration. Gross clinical signs of fever, mild to severe malaise, anorexia, diarrhea, dehydration, and generalized soreness appeared around Day 42, peaked at Day 56, and disappeared by Days 70-84 post-infection. Leukopenia, associated initially with a mild lymphopenia and later by both a mild lymphopenia and a severe neutropenia, appeared 14-28 days following infection, troughed at Day 56, and persisted thereafter. The CD4+:CD8+ T cell ratio started to decrease around Day 28, reaching a nadir at Days 56-70. This decrease was due to a decline in the absolute numbers and percentage of CD4+ T cells and an increase in the percentage of CD8+ T cells. Significant histopathologic lesions included myeloid hyperplasia between Days 56-70 post-infection; thymitis with cortical involution and follicular hyperplasia starting at Day 42; lymphoid hyperplasia of peripheral and mesenteric nodes, spleen and tonsils beginning around Day 42; typhlitis most evident from Day 56 onward, and an interstitial nephritis and pneumonitis that was most intense after Day 42. Virus was isolated from peripheral blood mononuclear cells (PBMC) beginning 2 weeks post-infection, and plasma viremia appeared 1 week later. Plasma and PBMC-associated viremia peaked at 42-56 days following infection and decreased abruptly thereafter. Proviral DNA was detectable as early as 5 days after infection in blood leukocytes and after 10 days in other organs. The central nervous system, lungs, thymus, tonsils and mesenteric lymph nodes were the earliest sites of virus localization. Antibodies to the FIV capsid protein appeared 14 days following infection and reached peak levels by Days 42-56. Abnormalities occurring during the primary stage of FIV infection were consistent with those described for acute simian and human immunodeficiency virus-induced disease.
 ...
PMID:An experimental study of primary feline immunodeficiency virus infection in cats and a historical comparison to acute simian and human immunodeficiency virus diseases. 785 70

Examinations were made on erythrocytes, thrombocytes, leukocytes, lymph nodes, thymus, haemal nodes and bone marrow in field cases of East Coast Fever (ECF) in Tanzania. Seventy-six clinically sick short-horn Zebu and Taurine-Zebu crosses, positive for Theileria parva piroplasms and schizonts and 55 apparently healthy cattle were studied. The syndrome observed was characterised by severe pancytopenia, with massive normocytic, normochromic anaemia, panleukopenia and thrombocytopenia, but no reticulocytes in peripheral blood. The erythrocyte and leukocyte counts, haematocrit and haemoglobin concentrations were greatly decreased compared with those of the healthy cattle. The means +/- SD (with values of healthy cattle in parentheses) were 2.85 +/- 1.10 (6.04 +/- 1.58) x 10(12) l-1, 2.78 +/- 1.70 (10.59 +/- 4.16) x 10(9) l-1, 0.19 +/- 0.06 (0.31 +/- 0.054)1 l-1 and 4.07 +/- 1.62 (7.29 +/- 1.39) mmol l-1 respectively. Lymphoproliferation was low, while lymphocyte destruction (lymphocytolysis) was high. There were very few small schizonts in parotid and prescapular glands. Lymphocytes were extensively destroyed in medullary cords, germinal centres of lymph nodules in cortex and paracortical regions of lymph nodes and haemal nodes. The bone marrow was hypocellular, with only a few haematopoietic precursor erythroid, granulocytic and thrombopoietic cell series. All stages of prorubriblasts and rubricytes had granulated nuclei, some with schizonts. Infection of erythrocytes by merozoites appeared to take place in precursor stages. The destruction of erythroblasts, rubricytes and other haematopoietic cells resulted in anaemia without reticulocytosis, haemoglobinuria and jaundice, accompanied by panleukopenia of extreme neutropenia, lymphopenia and eosinopenia. This indicated that this T. parva strain differs from previously described buffalo- or cattle-derived T. parva infections in causing both haemoproliferation and lymphoproliferation by extensive haematopoietic cell destruction and lymphocytolysis. In cattle- and buffalo-derived T. parva infections, anaemia is normally mild and there are numerous large schizonts in the former.
 ...
PMID:Severe anaemia due to haematopoietic precursor cell destruction in field cases of East Coast Fever in Tanzania. 807 8

The leishmaniases are global health problems that affect both humans and animals. The availability of nonhuman primate models is desirable for such important areas as testing candidate vaccines and newly developed chemo- and immunotherapeutic agents. Visceral leishmaniasis was experimentally induced in African green monkeys (Cercopithecus aethiops) by intravenously inoculating 10(7) amastigotes/kg of body weight of either Leishmania leishmania donovani of human origin (group 1) or L. l. infantum of canine origin (group 2). The infected monkeys were monitored for 12 weeks. The monkeys developed persistent infections, became emaciated, and lost between 9 and 22% of their body weights. Splenomegaly developed by 6 to 10 weeks postinfection. All infected monkeys developed normocytic, normochromic anemia (3.5 to 3.8 x 10(6)/microliters), leukopenia (3,000 to 3,700/microliters), and neutropenia of varying severity. Hyperproteinemia with hyperglobulinemia (5.22 to 6.12 g/dl) was present in all monkeys to various degrees. Antibody responses gradually increased to peak values at 2 weeks postinfection in the L. l. donovani group and by 6 weeks postinfection in the L. l. infantum group. Lymphocyte blastogenesis proliferation responses were mildly decreased in all infected monkeys at 10 to 12 weeks postinfection. Parasite numbers were consistently higher in the livers than in spleens, and parasites were present in smears or cultures of the liver, spleen, bone marrow, and lymph nodes. Contrasting data between the two groups included 20-fold-higher parasite numbers in the livers (3.23 to 9.48 x 10(9)) and 39-fold-higher parasite numbers in the spleens (6.7 x 10(8) to 2.69 x 10(9)) of group 1. Granulomatous inflammatory reactions of various severity and intensity were observed in the liver, spleen, lymph nodes, thymus, and bone marrow of all infected monkeys. Within the granulomatous inflammatory reactions, clusters of macrophages, often containing amastigotes, were present. The morphologic changes in the bone marrow suggested a myelophthisic disease and those in lymph nodes and spleen suggested a B-cell proliferation. The clinicopathologic changes, mild suppression of cell-mediated immunity, and high antibody response in all infected monkeys indicated that African green monkeys can be a useful laboratory model for studying the clinicopathologic and immunopathologic changes induced by both L. l. donovani and L. l. infantum.
 ...
PMID:Comparative susceptibility of African green monkeys (Cercopithecus aethiops) to experimental infection with Leishmania leishmania donovani and Leishmania leishmania infantum. 845 77


1 2 3 Next >>