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Biomedical subjects

R A Joyce

Publications and source records attributed to R A Joyce.

At least 19 recordsLinked to original sources
PubMed1992

Neutrophil function in chronic neutrophilic leukemia: defective respiratory burst in response to phorbol esters.

Functional analyses were performed on neutrophils isolated from 6 patients from two institutions who displayed features of chronic neutrophilic leukemia (CNL). These neutrophils demonstrated a consistent deficiency (44 +/- 8% of control values) in superoxide anion (O2-) production in response to the phorbol ester, phorbol myristate acetate (PMA). O2- production in response to chemotactic peptides was near normal (82.3 +/- 10.7% of control values). Bacterial killing was normal in the two patients studied, and chemotaxis was diminished in response to zymosan-activated plasma and to high concentrations of chemotactic peptides in the patients studied. Cytosolic C kinase activity was decreased in one of the two patients studied. These results suggest that a deficient O2- release in response to PMA is a hallmark of neutrophils in CNL and may provide a diagnostic indicator of this condition.

Aged↗
PubMed1991

Atypical (7;19) translocation in acute myelomonocytic leukemia.

Chromosome studies were carried out after a 24-hour harvest of unstimulated bone marrow aspirate cell cultures from a 75-year-old male with a clinical diagnosis of acute myelomonocytic leukemia (FAB M4). Analysis of nine cells after trypsin-Giemsa banding (GTG) revealed two cell lines with a mosaic chromosome pattern, 46,XY/46,XY,t(7;19)(q22;p13.3). A review of the recent literature reveals one case of childhood ALL with a 46,XY/46,XY,t(7;19)(q11;q13) chromosome pattern [1] and a 46,XY,t(3q;11q),t(7q;19p),t(15;17)(q26;q22) in one patient with ANLL (FAB M3) [2]. The t(7;19)(q22;p13.3) seen in our case has not been reported as the sole specific clonal chromosome rearrangement in myeloid neoplasia. Interestingly, the plasminogen activator inhibitor type I, multi-drug resistance, and erythropoietin genes are located at band 7q22 and the insulin receptor gene is located at band 19p13.3. Both sites contain fragile site loci. The possible role of these fragile sites, genes, or other genes in the rearrangement can only be surmised.

Aged↗
PubMed1984

Sequential effects of lithium on haematopoiesis.

The administration of lithium salts to haematologically normal subjects is associated with increased blood neutrophil concentrations and marrow neutrophil production and with enhanced release of colony stimulating activity (CSA) required for growth of granulocyte-macrophage progenitor cells (CFU-GM) in vitro. To examine the haematopoietic changes associated with lithium salts, mice were given LiCl daily. Blood neutrophils and serum CSA levels increased as did blood platelet concentrations. These increments were preceded by expansion of marrow neutrophil production and increased concentrations of CFU-GM as well as progenitor cells for megakaryocytes (CFU-M) and erythrocytes (BFU-E and CFU-E). An earlier and sustained increase of transplantable pluripotential stem cells (CFU-S) was detected beginning at day 2 of lithium administration. The sustained increase of CFU-S with lithium was not associated with detectable changes of endogenous stem cells (E-CFU) suggesting that a portion of the stem cell pool is resistant to the proliferative effects of lithium. These studies indicate that lithium acts initially to directly or indirectly increase marrow CFU-S with later increments of progenitor cells. The more sustained increase of blood neutrophils with lithium administration may be the result of subsequent increments of CSA resulting in enhanced marrow granulocyte production.

Animals↗
PubMed1983

The hematopoietic effects of lithium.

The observation that patients treated with Li for manic-depressive illnesses develop an associated leukocytosis has led to a series of experimental and clinical studies of the hematopoietic effects of this simple molecule. Increases in blood neutrophils, eosinophils and perhaps monocytes are observed routinely when persons with an apparently normal hematopoietic system are exposed to "therapeutic" doses of the drug. Blood platelets tend to be increased, but lymphocytes and erythrocytes are unaffected. Neutrophilia reflects a true increase in the total number of mature neutrophils in all body compartments and is due to increased production. Neutrophil function generally is unaffected by Li. In man or in other mammals, certain classes of hematopoietic stem cells are increased by Li administration. Extensive studies of the effect of Li have been carried out in cultures of cells producing colonies of neutrophils and macrophages (CFUNM) in semisolid media. The colony-forming cell itself is little affected by Li. Cells which produce the factor essential for production of normal CFUNM (CSF) are stimulated to produce more CSF by the presence of Li. Studies of changes in vivo in CSF levels yield somewhat conflicting results; serum CSF being increased in some but not in others. Thus, it is not clear if the effect of Li on cell production in vivo reflects a direct effect on granulocytic precursors, including stem cells, or is mediated by stimulation of a feed-back loop (or both). A number of trials of Li therapy designed to modify induced neutropenia or to correct existing neutropenia are reviewed. Although many of these are very difficult to interpret, there is some reason to be optimistic concerning an eventual role for Li therapy of certain diseases associated with hematologic abnormalities.

Adult↗
PubMed1980

Neutrophil kinetics in Felty's syndrome.

In 19 patients with Felty's syndrome, marrow production of neutrophils and neutrophil distribution were studied. Despite accelerated marrow release and disappearance of mature blood neutrophils, there was little or no increase in the marrow mitotic pool or in vitro progenitor cells. Only two patients had an increase in marrow neutrophils and precursors. Antineutrophil antibody was detected in seven of nine patients studied. Neither abnormal margination of blood neutrophils nor impaired marrow release of cells was detected. Skin exudate cellularity tended to correspond to prior history of infections, asymptomatic patients having more cellular exudates. Sustained neutrophil increments were observed in six of 10 patients following splenectomy, but in no patient did neutrophil kinetics return completely to normal. Three of four patients who failed to respond to splenectomy with sustained increments in blood neutrophils had a reduced mass of marrow neutrophils and neutrophil precursors when studied prior to splenectomy. No diminution in neutropenia was observed in any of five patients treated with lithium carbonate. This study indicates that multiple factors are involved in the pathogenesis of neutropenia in Felty's syndrome. In particular, neutropenia was associated with inadequate marrow granulocytopoiesis. The severity of the impairment, as determined by the mass of marrow neutrophils and precursor cells, may be useful in predicting response to splenectomy.

Aged↗
PubMed1980

Asplenia and abnormal neutrophil kinetics in chronic idiopathic neutrophilia.

Chronic idiopathic neutrophilia is a rarely recognized finding in otherwise healthy subjects. Described here is a case, not previously reported; in which the patient also had congenital asplenia. Studies carried out to determine the mechanism for the neutrophilia are also described. The results show that the patient's neutrophilia was associated with an enlarged circulating pool of neutrophils, increased production and utilization of neutrophils and a short blood granulocyte survival. The findings differ completely from those observed in patients with chronic idiopathic neutrophilia and intact spleens. The results suggest that (1) the mechanism for neutrophilia in patients with chronic idiopathic neutrophilia varies and depends upon the presence or absence of the spleen, and (2) the spleen has a role in the control of neutrophil production, distribution and utilization.

Bone Marrow Cells↗
PubMed1980

Estrogens and hematopoiesis: characterization and studies on the mechanism of neutropenia.

The effect of ES upon hematopoiesis was studied following 4 to 24 weeks of administration in adult female mice. ES produced osteosclerosis, hepatomegaly, splenomegaly with an increase in splenic erythropoiesis mild anemai, and a relatively stable, moderately severe neutropenia. Intact and splenectomized mice failed to develop hepatic hematopoiesis to compensate for these blood changes. The neutropenia was characterized by a proportionally normal-sized marginal granulocyte pool and a reduced marrow granulocyte reserve in the marrow, cellularity, peroxidase-positive cells. CFU-S, and CFU-GM declined during 4 to 12 weeks of study in the same study period, splenic granulocytopoiesis increased as measured by these perameters, but it only partially compensated for the neutropenia. CSA was present in serum, and no inhibitors of in vitro granulocytopoiesis were detected. The direct addition of E3S to normal murine marrow cells in vitro failed to inhibit CFU=GM proliferation. Daily ES administration failed to inhibit in vivo granulocytopoiesis in diffusion chambers. These studies suggest that ES-induced neutropenia is not due to direct inhibition of CFU-S or CFU-GM proliferation or differentiation to mature granulocytes and by implication, suggest that it may be mediated through effects on the hematopoietic microenvironment.

Agranulocytosis↗
PubMed1979

Visualizing the marrow granulocyte reserve.

The MGR, the pool of band and segmented neutrophils from which sudden demands for extra blood neutrophils are met, has been studied by measuring blood neutrophil increments following administration of endotoxin, corticosteroids, or etiocholanolone. Alternatively its size may be estimated from marrow differential counts with or without estimates of marrow mass. In 34 studies of 31 patients with diverse causes of neutropenia, measurements were made of the MGR comparing endotoxin response and differential counts of marrow aspirates coupled with estimates of absolute marrow mass derived from EIT rate. Responses to endotoxin were normal in 10 studies and subnormal in 24. The factor which best predicted endotoxin response was the percent of marrow neutrophils and neutrophil precursors which were band and segmented forms. All responders to endotoxin had greater than 25% marrow neutrophils and neutrophil precursors that were band and segmented; 20 to 21 subjects with less than a normal response to endotoxin had less than 25%. These studies suggest that no further information is gained by measuring endotoxin response in neutropenic patients who have a reduced percent of band forms and segmented neutrophils in marrow aspirates.

Adolescent↗
PubMed1979

Splenic granulopoiesis in mice following administration of cyclophosphamide.

The adult mouse spleen retains granulocytic progenitor cells that are capable of proliferation and maturation. In mice given cyclophosphamide, spleen weight and cell content increased. In vitro granulocyte progenitor cells increased more than 300-fold in the spleen and remained elevated 14 days following cyclophosphamide. Proliferative and nonproliferative granulocytes were increased above controls until Days 21 and 28, respectively. In splenectomized mice, blood neutrophil recovery was delayed when compared to nonsplenectomized mice following cyclophosphamide. Although marrow cell number was similar in both groups, maximum marrow granulocyte progenitor cells were 2-fold greater in nonsplenectomized animals. These studies demonstrate that the murine spleen becomes a markedly granulopoietic organ and is a major contributor to recovery of granulocytes following cyclophosphamide. Splenic granulopoiesis should be taken into account in studies which measure toxicity of various agents in murine hematopoiesis.

Animals↗
PubMed1977

Corticosteroid effect on granulopoiesis in mice after cyclophosphamide.

Corticosteroids cause an enhanced return of granulopoiesis as measured by in vitro growth of granulocytic progenitor cells (CFU-C) in mice treated with cyclophosphamide. After methylprednisolone and cyclophosphamide, a greater than threefold increase in marrow CFU-C was measured on day 4 compared to mice given cyclophosphamide alone (29,700+/-200 vs. 8,400+/-700/humerus). The accelerated return of marrow CFU-C was observed with cyclophosphamide in doses of 200 and 450 mg/kg and methylprednisolone, 2-20 mg/kg, with no significant differences using >5 mg/kg, and was detected when dexamethasone was used in place of methylprednisolone. This effect was accompanied by similarly enhanced splenic granulopoiesis as measured by CFU-C concentration. Levels of colony stimulating activity did not differ in mice given methylprednisolone and cyclophosphamide or cyclophosphamide alone. Corticosteroids appear to enhance the return of CFU-C by altering the proliferative state of granulocytic progenitor cells. CFU-C survival to in vitro (3)HTdR suicide increased from 72+/-4% on day 1 after cyclophosphamide to 90+/-6% in animals given both cyclophosphamide and methylprednisolone. Increased survival after (3)HTdR suicide was also observed when methylprednisolone alone was given. After treatment with cyclophosphamide and methylprednisolone, blood neutrophils increased more rapidly and improved survival to infection with Candida albicans was observed. These studies demonstrate that corticosteroids have a beneficial effect on marrow regeneration after myelotoxic chemotherapy with cyclophosphamide and suggest that they act by altering cell cycle characteristics of granulocyte progenitor cells.

Animals↗
PubMed1976

Neutrophil kinetics in hereditary and congenital neutropenias.

Neutrophil production and distribution were studied in two families with autosomal dominantly inherited neutropenia to distinguish their illness from other neutropenic disorders. In addition to a reduced post-mitotic pool of bone-marrow neutrophils and neutrophil precursors, mitotic pool size was also reduced, ranging from 1.1 to 2.9 X 10(9) cells per kilogram (normal, 3.8 +/- 0.4 X 10(9) per kilogram). In vitro committed stem cells were reduced as well, ranging from 2 to 12/10(5) marrow cells (normal, 30 to 120/10(5)). In three patients neutrophil counts were observed to return to normal when they were adults. In one such subject studied, however, both the mitotic pool of neutrophil precursors and marrow committed stem cells were reduced. These abnormalities were in contrast to studies of a patient with chronic benign neutropenia of childhood and an infant with Kostmann-type congenital neutropenia, both of whom had increased marrow committed stem cells. These studies demonstrate several different mechanisms for production of neutropenia in these syndromes.

Adolescent↗