Biomedical subjects

A Harlow

Publications and source records attributed to A Harlow.

6 recordsLinked to original sources

PubMed2005

Mutations in KIT and RAS are frequent events in pediatric core-binding factor acute myeloid leukemia.

Activating mutations in RAS and receptor tyrosine kinases such as KIT and FLT3 are hypothesized to cooperate with chimeric transcription factors in the pathogenesis of acute myeloid leukemia (AML). To test this hypothesis, we genotyped 150 pediatric AML samples for mutations in KIT (exons 8, 17), NRAS and KRAS (exons 1, 2) and FLT3/ITD. This is the largest cohort of pediatric AML patients reported thus far screened for all four mutations. Of the children with AML, 40% had a mutation in KIT (11.3%), RAS (18%) or FLT3/ITD (11.1%), and 70% of cases of core-binding factor (CBF) leukemia were associated with a mutation of KIT or RAS. Mutations in RAS or FLT3/ITD were frequently found in association with a normal karyotype. Patients with a FLT3/ITD mutation had a significantly worse clinical outcome. However, the presence of a KIT or RAS mutation did not significantly influence clinical outcome. We demonstrate that KIT exon 8 mutations result in constitutive ligand-independent kinase activation that can be inhibited by clinically relevant concentrations of imatinib. Our results demonstrate that abnormalities of signal transduction pathways are frequent in pediatric AML. Future clinical studies are needed to determine whether selective targeting of these abnormalities will improve treatment results.

Acute Disease↗

PubMed2001

Addressing the needs of adolescent children when a parent becomes aphasic: one family's experiences.

There are several reports of the psychosocial effects of aphasia on family members and of factors that may influence a family's emotional adjustment. Most of these, however, have included only spouses or the adult children of individuals with aphasia. Therefore, to address how children of adolescent age or younger react to and cope with parental aphasia, this article provides an account of one family's experiences with stroke and aphasia. Specifically, the impact of a father's aphasia on his adolescent daughter as well as how the parents attempted to help their daughter adjust during acute and chronic recovery phases are described.

Journal Article↗

PubMed1998

Pupil responses to stimulus color, structure and light flux increments in the rhesus monkey.

Visual stimuli that isolate pupil color and pupil grating responses in human vision have been used to investigate the properties, of stimulus-specific pupil responses in the rhesus monkey. We measured and compared pupil responses to light flux increments, isoluminant chromatic stimuli, and gratings of equal and lower space-averaged luminance. The parameters investigated were luminance contrast and chromatic saturation. The results demonstrate clearly the existence of pupil color, pupil grating and pupil light reflex responses in the rhesus monkey. Comparison of pupil color and pupil grating responses of equivalent amplitude reveals similar onset response latencies. However, both are approximately 40 ms longer than the corresponding pupil light reflex latency. In general these pupil responses are qualitatively similar to those observed in humans. However, when compared to equivalent human data, pupil onset response latencies are some 80-100 ms shorter and the pupil shows more rapid recovery from constriction.

Adult↗

PubMed1991

Factors affecting visual sensitivity in a hemianopic subject.

A well-studied subject with visual cortex damage (G.Y.) was tested in his hemianopic field with temporally modulated sinusoidal and square-wave gratings. The purpose was to use an extended range of parameters to obtain a detailed spatiotemporal specification of his residual vision and to try to resolve the discrepancy between negative findings of Hess and Pointer (1989) and previous positive claims. Both the spatial and temporal parameters could be Gaussian-weighted. Detection as a function of spatial frequency, contrast, temporal modulation frequency, stimulus size, and slope of the temporal and spatial Gaussian functions was investigated using a two-alternative forced-choice procedure. The most important parameters for this subject were found to be the slope of the temporal Gaussian function and the size and contrast of gratings. With optimum parameters he could reliably achieve a score of 95-100% correct in his 'blind' field. The results are consistent with earlier studies of this subject, especially his ability to respond to moving stimuli, and also may account for why negative results had been reported for him when particular fixed parameters were used.

Contrast Sensitivity↗

PubMed1980

In vitro palmitate and glucose metabolism in the postmature fetus.

Fetuses from term and postmature rabbits were obtained and their livers incubated with palmitate-1-14C in room air. The net incorporation of the fatty acids into ketone bodies, lipids, and Co2 was measured at fixed and variable concentrations of cold glucose. Data from postmature liver show that lipid synthesis is decreased, 14CO2 production is increased, and ketone body formation is unchanged when compared with data from the term liver. The addition of cold glucose to a constant concentration of palmitate-1-14C causes a slight increase in lipid synthesis in thepostmature liver, in contrast to a decrease in the term liver. The experimental results indicate that liver lipid synthesis and glucose utilization are diminished in the postmature preparation. This suggests that the postmature fetal liver responds to the decreased availability of free fatty acid from the placenta and to the increasing hypoxia by metabolic adaptations resembling those observed during fasting and tissue hypoxia. These changes are somewhat similar to those observed in the neonate before the onset of breast-feeding. Fetal metabolism is, therefore, responsive to changes in placental transfer of fatty acids and to postmaturity.

Animals↗

PubMed1979

Placental uptake and transfer of lipid in the postterm rabbit.

Gonadotropin-injected pregnant rabbits were delivered by cesarean section near term (30 days after conception (term, 31 days) and 3 1/2 and 4 days post term. Lipid metabolism of the postterm and near-term fetus was compared. Fetal and placental uptake of radioactivity and rate of lipid entry into the fetus, as well as fetal and maternal plasma free fatty acid (FFA) specific activities (at equilibrium) were determined following a single maternal injection of [1-14C]palmitate (50 muCi) administered at cesarean section. Evidence of placental malfunction in the postterm period includes decreased placental uptake and transport of labeled FFA occurring while maternal and fetal FFA dynamics (half times) remain unchanged and a loss in "organization": The strong positive correlation (p less than 0.001) between placental uptake and transfer to the fetus at 30 days' gestation is lost 5 days later. A comparison of maternal and fetal plasma FFA specific activities indicates a substantial (62%) near-term fetal contribution to its own circulating FFA pool. Total plasma FFA is elevated in the postterm fetus concomitant with a decreasing maternal supply. A postterm fetus must therefore contribute lipid from its own reserves (probably liver) in excess of amounts attributed to a near-term fetus, i.e., greater than 62%.

Animals↗