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Biomedical subjects

D Ryan

Publications and source records attributed to D Ryan.

At least 91 records · Page 5Linked to original sources

In vitro and in vivo killing of acute lymphoblastic leukemia cells by L-asparaginase.

L-Asparaginase (ASNase) is a potent antileukemic enzyme routinely used in the treatment of children with acute lymphoblastic leukemia. As part of investigations of the biological activity of ASNase, we have developed techniques which measure the in vitro and in vivo cell killing ability of ASNase. To study the effect of ASNase on in vitro survival of primary lymphoblasts, bone marrow mononuclear cells obtained from untreated patients with acute lymphoblastic leukemia were cultured with and without ASNase. After 5 days, viable cells were counted using trypan blue exclusion to calculate total cell kill due to ASNase. Propidium iodide exclusion, leukemia cell surface antigens, and flow cytometry were used to determine leukemia cell kill due to ASNase. Comparison of leukemia cell kill and total cell kill showed a direct linear relationship (n = 24, r = 0.7), preferential killing of leukemia cells by ASNase (slope = 0.66), and that use of leukemia cell surface markers yielded a more accurate measurement of leukemia cell killing. ASNase at concentrations from 0.0001 to 0.1 IU/ml had equal effects on extent of leukemia cell killing (P = 0.3 to 0.7), suggesting the absence of a dose response at the ASNase concentrations tested. As a measure of the in vivo response to ASNase treatment, the number of viable bone marrow leukemia cells in the patient prior to and 5 days after treatment with ASNase was measured as the product of (% of rhodamine 123 fluorescent [viable] cells) x (absolute leukemic infiltrate). The change which occurred in the viable leukemic infiltrate was the same for patients whether they received 25,000 or 2,500 IU/m2 of ASNase as a single drug. There was a linear correlation (n = 8, r = 0.9) between in vivo and in vitro leukemia cell killing by ASNase. Thus, the in vitro assay described here can be used to predict in vivo sensitivity to ASNase in acute lymphoblastic leukemia.

Asparaginase↗

Mean and quasideterministic equivalence for linear stochastic dynamics.

In linear, stochastic dynamics it is shown that the quasideterministic population size is equivalent to the mean population size. The quasideterministic dynamics are defined by the conditional infinitesimal mean of the process. The stochastic component of the dynamics includes both Gaussian and Poisson white noise, with amplitude coefficients proportional to the population size. Generalizations are given for nonautonomous coefficients and for distributed Poisson jump amplitudes. A counter example--an exactly integrable nonlinear jump model--shows that the equivalence result does not hold for nonlinear stochastic dynamics.

Linear Models↗

A parotid fistula and sialocele complicating temporomandibular joint surgery.

A case of a persistent parotid fistula and sialocele following temporomandibular joint surgery is described. This rarely reported complication is postulated to result from pre-existing bucco-masseteric obstruction of parotid outflow causing raised intraductal pressure in the patient. Following unsuccessful conservative management, the patient was cured by a 5-day course of restricted oral intake and propantheline bromide.

Adult↗

Resuscitation and petechiae.

Petechiae can be important corroborative evidence of asphyxia, but are also seen in persons who have died of other means. It is not uncommon to encounter them in cases in which cardiopulmonary resuscitation has reestablished blood flow and pressure in small vessels already damaged by hypoxia resulting in the formation of petechiae. This report documents some representative cases.

Adolescent↗

Optimal harvesting of a logistic population in an environment with stochastic jumps.

Dynamic programming is employed to examine the effects of large, sudden changes in population size on the optimal harvest strategy of an exploited resource population. These changes are either adverse or favorable and are assumed to occur at times of events of a Poisson process. The amplitude of these jumps is assumed to be density independent. In between the jumps the population is assumed to grow logistically. The Bellman equation for the optimal discounted present value is solved numerically and the optimal feedback control computed for the random jump model. The results are compared to the corresponding results for the quasi-deterministic approximation. In addition, the sensitivity of the results to the discount rate, the total jump rate and the quadratic cost factor is investigated. The optimal results are most strongly sensitive to the rate of stochastic jumps and to the quadratic cost factor to a lesser extent when the deterministic bioeconomic parameters are taken from aggregate antarctic pelagic whaling data.

Animals↗

Toronto Alexithymia Scale: relationship with personality and psychopathology measures.

The Toronto Alexithymia Scale (TAS) is a 26-item self-report measure of alexithymia with good internal consistency and test-retest reliability, and a factor structure congruent with the alexithymia construct. This study assesses the construct validity of the scale by examining its relationship with several personality and psychopathology measures. In a sample of 81 college students, the TAS correlated strongly and positively with a measure of hypochondriasis but negatively with measures of psychological mindedness and 'need for cognition'. There were low-magnitude correlations between the TAS and measures of self-depreciation, social introversion, persecutory ideation, and impulse expression, but no correlation with a measure of denial. These results indicate that the TAS is assessing adequately the theoretical domain relevant to its item and factor structure.

Adolescent↗

Subpopulations of common acute lymphoblastic leukemia antigen-positive lymphoid cells in normal bone marrow identified by hematopoietic differentiation antigens.

Bone marrow samples from normal adults and children with nonhematologic malignancies not involving the marrow, acute lymphoblastic leukemia (ALL) in continued remission, and immune cytopenias were studied by two-color immunofluorescence (IF) and flow cytometry to characterize common acute lymphoblastic leukemia antigen (CALLA)-positive marrow lymphoid cells. Marrow was separated by Ficoll/Hypaque centrifugation followed by passage over a monoclonal antibody affinity column to remove myeloid cells prior to IF staining. A higher proportion of CALLA-positive cells was found in the pediatric marrows (mean, 33.7% +/- 6.3% SEM) than in the adult marrows (mean, 4.5% +/- 1.6% SEM). Two subpopulations of CALLA-positive cells identified by cell sorting to be of lymphoid morphology were found in both adult and pediatric marrows. A small subpopulation comprising 12.3% of the total CALLA-positive cells was characterized by a high intensity of CALLA, terminal deoxynucleotidyl transferase (TdT), and MY10 expression, but low B1, common leukocyte antigen, and peanut agglutinin receptor expression. The remainder of the CALLA-positive cells displayed low intensity of CALLA expression, positivity for the common leukocyte antigen, B1 and peanut agglutinin, and negative reaction with TdT and MY10. Both CALLA-positive subpopulations were positive for HLA-DR and the pan-B cell marker B4, but negative for cytoplasmic immunoglobulin, B2 and Leu 1. BrdU labelling studies showed that a similar proportion of cells in each subpopulation was in S phase. A slightly higher proportion of the strongly CALLA-positive cells possessed the morphologic features of high nuclear/cytoplasmic (N/C) ratio and prominent nucleoli. These studies suggest that a discrete maturation step occurs among CALLA-positive marrow lymphoid cells, resulting in the loss of TdT and MY10 expression, but gradual acquisition of the B cell marker B1 and the common leukocyte antigen. The presence of B4 antigen in nearly all CALLA-positive cells suggests that both subpopulations of normal CALLA-positive marrow cells are committed to the B cell lineage.

Adult↗

Hexachlorobenzene and substituted pentachlorobenzenes (X-C6Cl5) as inducers of hepatic cytochrome P-450-dependent mono-oxygenases.

Hexachlorobenzene (HCB) and 2,3,4,4',5-pentachlorobiphenyl induced a similar spectrum of cytochrome-P-450-dependent mono-oxygenase activities in the rat, including 4-dimethylaminoantipyrine N-demethylase, aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin O-deethylase (EROD). Levels of individual cytochrome P-450 isozymes and various mono-oxygenase activities in liver microsomes from rats treated with substituted pentachlorobenzene (X-C6Cl5) and 4'-substituted-2,3,4,5-tetrachlorobiphenyl (X-C12 H5Cl4) analogues demonstrated the remarkable effects of substituent structure on induction activities. The chloro- and bromopentachlorobenzenes induced hepatic microsomal 4-dimethylaminoantipyrine N-demethylase, AHH and EROD; the iodo-, fluoro-, acetamino- and nitropentachlorobenzene analogues together with pentachlorobenzene weakly induced both AHH and EROD (approximately 2-fold or less); and the remaining substituted pentachlorobenzenes tested (X = CH3, OCH3 and OH) were relatively inactive as inducers of microsomal mono-oxygenases. Substituent effects were observed for the induction of liver microsomal cytochromes P-450a, P-450b + e, P-450c, P-450d and total cytochrome P-450 by the X-C6Cl5 and X-C12H5Cl4 analogues. The chloro- and bromopentachlorobenzene analogues in both series induced total cytochrome P-450 and cytochromes P-450a to P-450d, whereas the hydroxy-, methyl- and methoxy-substituted analogues in both series were relatively inactive as inducers of cytochrome P-450. Iodo-, fluoro- and nitropentachlorobenzene were weak 3-methylcholanthrene-type inducers and, in contrast to the corresponding biphenyl analogues, had little or no effect on the induction of cytochromes P-450a, P-450c and P-450d.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Toward the development of a new self-report alexithymia scale.

Addressing methodological problems in the development of existing scales for measuring alexithymia, this study reports the development of a new self-report scale. The Toronto Alexithymia Scale (TAS) was devised with concern for theoretical congruence with the alexithymia construct, independence of social desirability response bias, and internal consistency. Initially, 41 items were administered to 542 college students. Twenty-six items meeting preestablished psychometric guidelines were retained. Factor analysis yielded four interpretable factors, all consistent with the construct. The scale demonstrated adequate split-half and test-retest reliability, and scores were not significantly associated with age, education, and socioeconomic status. These preliminary results suggest that the TAS may be used as a clinical screening device with psychiatric and general medical patient populations.

Adolescent↗

Alterations in red cell cation transport in hypertensive disorders of pregnancy.

The results of a cross-sectional study of alterations in red cell Na-Li countertransport in hypertensive disorders of pregnancy indicated that the mean value of Na-Li countertransport increased with gestational age in pregnant normotensives but not in pregnant chronic hypertensives. In addition the mean value was significantly higher in pregnancy-induced hypertensives than in pregnant normotensives. Moreover the mean value falls to a level observed in non-pregnant normotensives in the late post-partum period and no difference was observed between women with normal blood pressure and chronic hypertension. In a prospective study of 62 pregnant normotensives, Na-Li countertransport increased and the Na-K cotransport decreased throughout their pregnancy. Finally, increased amounts of endogenous digoxin-like substance can be detected in the sera from some pre-term infants.

Adult↗

Cytogenetic findings in congenital leukemia: case report and review of the literature.

The cytogenetic findings in a five-week-old female infant with acute lymphoblastic leukemia (ALL) are reported. Markers 11q - and 19 + were observed and considered to be due to an interstitial deletion of segment 11q13 to 11q23 of chromosome #11 and an insertion of this segment into the terminal region of the short arm of #19. Previously published banded cases of leukemic infants under one year of age have been summarized. A review of the data in these 29 cases suggests that the appearance of a normal karyotype in acute leukemia of infants (less than or equal to 1 year old) is much less common than in other categories of acute leukemia. Fourteen out of 29 cases (48%) had chromosomal abnormalities involving 11q. Seven of eight ALL cases had aberrations with a breakpoint at 11q22-23; six cases had t(4;11), one case had a del(11q) and ins(19p), and another had a t(1;22;4). All of three AMMoL cases had translocations involving the long arm of #11. The percentage of patients with t(4;11) and certain translocations involving 11q in infants with ALL or AMMoL, respectively, is higher than that seen in ALL and AMMoL in general. Eleven out of 12 cases (92%) of infant acute leukemias with chromosomal abnormalities involving 11q22-23 were five months old or less.

Chromosome Deletion↗