PubMed Health⌕ Search

Biomedical subjects

T D Miale

Publications and source records attributed to T D Miale.

At least 19 recordsLinked to original sources
PubMed1998

Novel enzymatic abnormalities in AML and CML in blast crisis: elevated leucocyte leukotriene C4 synthase activity paralleled by deficient leukotriene biosynthesis from endogenous substrate.

Leukotrienes (LT) are inflammatory mediators which can also exert regulatory effects on human myelopoiesis. We have studied the LT-producing capacity of freshly isolated leucocyte suspensions (containing blast cells in variable proportions) from 41 patients with acute myeloid leukaemia (AML) or chronic myeloid leukaemia (CML) in blast crisis (CMLbc) at diagnosis or relapse/resistant disease. Leucocyte suspensions from 19/29 AML patients (66%), and 2/12 CMLbc patients (17%; P = 0.012) demonstrated deficient capacity to synthesize LT from endogenous substrate after ionophore A23187 stimulation. Thus, these cells produced < 8 pmol LTB4+LTC4/10(6) cells (< 20% of mean LT formation in leucocyte suspensions from 18 healthy subjects). Addition of exogenous arachidonic acid did not normalize the LT synthesis in poor-producing cell suspensions. Purified, morphologically mature granulocytes from two AML patients also failed to produce normal amounts of LT. In leucocyte suspensions from the remaining 20 AML/CMLbc patients A23187 provoked LT biosynthesis, with markedly increased production of LTC4, but decreased LTB4 formation. Furthermore, elevated conversion of exogenous LTA4 to LTC4 was noted in the patient samples, independent of their capacity to produce LT after A23187 stimulation. The percentage of blast cells in patient white blood cell differential counts correlated inversely with ionophore-induced LT synthesis, but positively with the conversion of exogenous LTA4 to LTC4. The results suggest elevated LTC4 synthase activity and suppressed 5-lipoxygenase activity as novel enzymatic features of myeloid leukaemia patients with immature phenotype.

Acute Disease↗
PubMed1996

Efficacy and toxicity of radiation in preparative regimens for pediatric stem cell transplantation. II: Deleterious consequences.

There has been a dramatic improvement in the treatment of both allogeneic and autologous stem cell transplants, especially in children and young adults. However, attempts to apply more intensive conditioning treatments to the more refractory pediatric malignancies have also increased the risks of deleterious consequences. This review examines the risks, and reports important variations in the toxic effects of using different conditioning techniques.

Child↗
PubMed1995

Efficacy and toxicity of radiation in preparative regimens for pediatric stem cell transplantation. I: Clinical applications and therapeutic effects.

Here, we review the role of total body irradiation in the treatment of children with bone marrow transplantation, as well as alternative sources of stem cells. We were unable to demonstrate any clear superiority of TBI-containing preparative regimens, but we were able to find a few definitive reports of significantly enhanced toxicity or important variations in control of the underlying primary diseases, in comparing TBI-based regimens, with those containing only chemotherapy.

Adult↗
PubMed1994

Neuroblastoma stage IV-S.

A review of stage IV-S neuroblastoma is provided. The possible uses of prognostic features to guide treatment options in this group of infants with neuroblastoma are suggested. The biologic basis for the spontaneous regression of widespread tumor involvement in some infants with stage IV-S neuroblastoma is discussed. The reasons that some infants with IV-S disease progress to a fatal outcome, while most undergo maturation or involution and eventual long term cure are suggested. The influence of such factors as age at diagnosis, clinical staging, and tumor biology on eventual outcome are covered. Biological variables and markers discussed include: genetic (cytogenetics (1p deletions), nuclear genomic content), molecular biologic (N-myc oncogene amplification, mdr-1, ras, and trk, gene expression), immunological (major histocompatibility antigen density, cellular and humoral immunity), and biochemical (creatine kinase isoenzyme profile, neuron specific enolase, ferritin, chromatograffin, lactic acid dehydrogenase and catecholamine levels).

Child↗
PubMed1986

Natural killer cell activity and ultrastructure in myeloproliferative reactions in infants with Down's syndrome.

In some infants with Down's syndrome, the circulating mononuclear population, when viewed with conventional and electron microscopy, contains many cells that closely resemble leukemic blast cells. In contrast with true leukemia, however, most of these infants with the "leukemia-like reaction in Down's syndrome" (LLR-DS) enter spontaneous remissions. We therefore investigated the natural resistance of such infants to hematological malignancy in vitro by means of natural killer cell assays. Mean natural killer cell determinations in four infants with LLR-DS were 17.5 +/- 9.2% and 37.6 +/- 18.5% against K-562 and Molt-4 target cells, respectively, at diagnosis. Later, during remission, these values were 34.3 +/- 14.3% against K-562 and 32.2 +/- 15.6% against Molt-4. The mean percentage lysis of Molt-4 both at diagnosis and during remission was greater (p less than 0.05) in LLR-DS than in children with acute lymphocytic leukemia and acute myelogenous leukemia at diagnosis. Natural killer cell activity levels in these LLR-DS patients were similar to levels obtained in other infants with Down's syndrome who were hematologically normal, as well as levels obtained in normal control specimens. Two of these LLR-DS patients progressively developed acute myelogenous leukemia with ultrastructural abnormalities several months later; one of these also developed another karyotype abnormality. Both remain in long-term remission exceeding 48 months.

Acute Disease↗
PubMed1984

Retrospective analysis of 58 children with retinoblastoma.

We performed a retrospective analysis of 58 children with retinoblastoma seen at the University of Illinois at Chicago between 1960 and 1982. Our findings showed an almost equal distribution by sex, a predominance (69%) of white patients, and a common presenting symptom (70%) of leukocoria, with (22%) or without (48%) strabismus. Unilateral involvement was noted in 35 patients (60%). Of the 23 (40%) bilaterally affected children, 19 had simultaneous involvement at the time of diagnosis. All bilateral and 90% of the unilateral cases were diagnosed before age five years. Family history was positive for retinoblastoma in five bilateral and one unilateral case. At the time of diagnosis, 35 patients had stage V disease (Reese-Ellsworth classification, Table 1). Depending on the stage of disease treatment included enucleation, radiation, and chemotherapy. Mortality was 25% from 1960 to 1974, and zero thereafter.

Age Factors↗
PubMed1983

Decreased natural killer cell activity in children with untreated acute leukemia.

Natural killer cell activity was evaluated in children with acute lymphocytic and acute myelogenous leukemia. Peripheral blood mononuclear cells isolated at the time of diagnosis and before initiation of therapy were mixed with 51Cr-labeled K562 or MOLT-4 target cells at a ratio of 100:1. In 13 consecutive cases of acute lymphocytic leukemia, the mean percentage of lysis of K562 cells (15.0%) was significantly below that of adult (49.8%) and age-related controls (35.9%). A similar pattern was observed against MOLT-4 targets (acute lymphocytic leukemia, 11.3%; adults, 39.8%; and pediatric controls, 28.4%). The mean activity in 8 cases of acute myelogenous leukemia was also markedly reduced (6.8% versus K562 and 6.0% versus MOLT-4). Linear regression analyses of white blood cell, lymphocyte, and leukemia blast counts failed to demonstrate any correlation between peripheral cell counts and natural killer cell activity. Thus, it would not appear that the observed decrease in lysis was due merely to dilution of effectors with blasts. The lytic activity of cells isolated from patient blood was significantly lower than that from cells isolated from an equal volume of blood from a normal adult. These results suggest that the decreased natural killer cell activity is not explained by simple dilution. Instead, they indicate an absolute decrease in lytic potential. Additional experiments have precluded suppressor cell involvement and competitive inhibition of blasts with target cells as possible causes for depressed lysis.

Adolescent↗
PubMed1982

Surface Ia-like expression and MLR-stimulating capacity of human leukemic myeloblasts: implications for immunotherapy and prognosis.

Surface Ia-positive cells were found to vary from 0 to 100% in initial blood specimens from 37 adults with acute myelogenous leukemia (AML). When myeloblasts from 19 patients were tested against panels of lymphocytes from 5 to 19 normal donors, mean stimulation indices ranged from 1 to 60. Some leukemic myeloblasts strongly stimulated most allogenic responder lymphocytes whereas others produced almost no stimulation. The addition of antibody against human Ia to 28 mixed leukocyte reaction (MLR) combinations resulted in significant inhibition (p less than 0.001) of 3H-thymidine incorporation. Testing of myeloblastic Ia may have clinical relevance because patients with greater than 50% Ia-positive myeloblasts had a significantly longer survival than patients with fewer Ia-positive myeloblasts (p less than 0.04).

Adult↗
PubMed1982

Elevation of natural killer activity and nonspecific immunity following injection of Listeria cell walls.

Mice given a single intraperitoneal injection of cell walls from Listeria monocytogenes (LCW) prior to challenge with Candida albicans or a mammary carcinoma showed significantly increased survival compared to saline injected controls. The cell walls were mitogenic for spleen cells in vitro. Levels of stimulation were lower than for Con A and PHA but comparable to those induced by LPS. Peritoneal exudative cells, but not spleen cells, harvested from mice injected with LCW showed significant elevation of natural killer (NK) cell activity as early as 1 day following injection. NK activity remained elevated for 10 days and then returned to normal levels by day 145. Macrophage phagocytic and tumorcidal activity in vitro did not appear stimulated. In overall comparison to commercial mitogens, LCW had lower levels of activity measured in vitro but equivalent or higher in vivo levels of protection.

Animals↗
PubMed1979

The role of monocytes in phagocytosis and mixed leukocyte reactivity in human acute myeloid leukemia.

Lymphocyte proliferation, as measured by incorporation of tritiated thymidine (3H-TdR), was significantly enhanced (p less than 0.01) when macrophages sensitized by target myeloblasts were added to monocyte-depleted lymphocyte fractions in the mixed leukocyte reaction (MLR) with human leukemic myeloblasts as stimulators and panels of normal lymphocytes as responders. Monocyte addition in the same concentration range to unfractionated lymphocytes resulted in highly significant facilitation (p less than 0.0001) of MLR response patterns to myeloblastic stimulation. However, with substitution of a different myeloblastic stimulator, this facilitation was not observed. At higher monocyte-lymphocyte ratios (1:15) the monocytes appeared to be capable of strongly inhibiting the MLR. Monocyte capacity to engulf and kill Candida albicans organisms was normal in acute myeloid leukemia (AML) patients given "immunotherapy" with BCG and leukemic cells.

Cell Separation↗
PubMed1978

A summer camp for children with cancer.

The prognosis for children with cancer has changed significantly over the past 10 years. Currently, it is anticipated that cure can be achieved in approximately 50% of newly diagnosed cases of childhood cancer. The quality of life for these children depends not only on their medical treatment but also on the successful management of the psychological problems related to their diagnosis. A summer camp was established in Florida as a part of our psychosocial rehabilitation program for pediatric cancer patients. Participating in the day-to-day camp life were 26 children with various forms of cancer. Each child not only had the opportunity to enjoy a normal out-of-door life style, away from their overprotective parents, but experienced daily contact with other children who shared a similarly stressful existence. It is felt the awareness gained through the realization that they were not along in their plight and the independence instilled through separation from parents was beneficial to each child. It is anticipated that future camps with the inclusion of psychological testing will provide us with the opportunity to further assess the need for psychosocial rehabilitation for the child with cancer.

Adolescent↗
PubMed1978

Semiquantitative computerized image analysis of fetal hemoglobin distribution patterns in sickle cell anemia and its variants.

Computerized, semiquantitative image analysis of 2913 erythrocytes from 29 young patients with sickle cell anemia and its variants was conducted utilizing a modified method for determination of fetal hemoglobin distribution by an acid elution procedure. Histograms of eight arbitrary levels of staining intensity, proportional to fetal hemoglobin levels, were analyzed in relationship to both computer-generated, mathematical parameters of erythrocytic shape abnormalities and clinical parameters of disease severity. Shifts in fetal hemoglobin distribution were observed in analysis of sequential specimens. An inverse correlation was observed between angularity of erythrocytes and their individual fetal hemoglobin content (p less than or equal to 0.05). A positive correlation was noted between growth percentiles and percentage erythrocyte ghosts by acid elution (p less than or equal to 0.01).

Anemia, Sickle Cell↗
PubMed1978

BCG as active immunotherapy in children with acute lymphoblastic leukemia in longstanding remission: positive effects on remission duration and immunologic parameters.

Currently at the University of Florida, 22/45 children and adolescents are long-term survivors in complete sustained remission of standard chemotherapy regimens and central nervous system prophylaxis. All such therapy was discontinued in these survivors at 36 months after diagnosis and they were given monthly inoculations of BCG of the Tice strain by tine technique. 19/22 of BCG-treated patients remain in remission for 12 to 44 + months after cessation of chemotherapy. 1/22 has suffered relapse. Immunological function tests have shown statistically significant increased lymphocyte responses to PPD in contrast to age-matched controls and normal siblings. A trend to earlier than expected return to normal in other immunological parameters, including absolute lymphocyte counts, intradermal skin tests, phagocytosis indices, PHA transformation, and E-rosette forming cells was also observed, coincident with the BCG treatment. Further study of the role of BCG in acute lymphoblastic leukemia patients after cessation of chemotherapy is encouraged.

Adolescent↗