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Biomedical subjects

D A Nelson

Publications and source records attributed to D A Nelson.

At least 73 records · Page 4Linked to original sources
PubMed1995

Morphologic characteristics of erythroleukemia (acute myeloid leukemia; FAB-M6): a CALGB study.

We have reviewed the clinical, morphologic, immunophenotypic, and cytogenetic features of 52 patients with erythroleukemia (FAB Cooperative Group; AML-M6) studied by the Cancer and Leukemia Group B (CALGB). The purpose of this study was to correlate morphology with the clinical features, immunophenotypes, and karyotypes of neoplastic cells, and with the response to therapy of patients with AML-M6. Thirty-three patients (63%) were male, median age 59 (range 16-81) years, 47 patients (90%) were white, and 42 patients (81%) had a performance status of < 2. Myelodysplastic changes were observed in at least 1 cell lineage in all cases, and in 2 cell lineages in 45 of 52 (86%) cases. Fifty percent or more of cases studied were positive for CD11b, CD13, CD15, CD33, glycophorin-A, and HLA-DR markers. Fourteen of 27 cases (52%) in whom karyotypic analyses were conducted had cytogenetic abnormalities. Five (19%) were simple (< 3 karyotypic abnormalities), while 9 (33%) were complex (> or = 3 abnormalities). We observed either a complete or partial loss of chromosomes 5, 7, or 12p, or the presence of trisomy 8, in 11 of 27 (41%) patients. Cases of AML-M6 were divided into group 1 (14 patients with bone marrow proerythroblasts and basophilic erythroblasts > 25% of all erythroblasts) and group 2 (38 patients with proerythroblasts and basophilic erythroblasts < or = 25% of all erythroblasts). We observed no significant differences between groups 1 and 2 in regard to sex, age, race, performance status, percentage of blood erythroblasts or myeloblasts, percentage of bone marrow erythroblasts, and periodic acid-Schiff (PAS) or myelodysplasia scores. Six of 6 (100%) patients of group 1, and 7 of 21 (33%) patients of group 2, had normal karyotypes (P = .006). Nine of 13 (69%) patients of group 1 and 15 of 33 (45%) patients of group 2 had a complete remission (CR) (P = .2). Eight of 11 (73%) cytogenetically normal patients achieved CR: 5 of 6 (83%) in group 1, and 3 of 5 (60%) in group 2. Five of 12 (42%) cytogenetically abnormal patients achieved CR. No difference in duration of survival (group 1, median = 4.6 months vs. group 2, median = 10.2 months; P = .93) was observed between the 2 groups. We conclude that AML-M6 is typified by multilineage involvement of hematopoietic cells. The morphology of erythroblasts in patients with AML-M6 may correlate with cytogenetic abnormalities and rate of CR.

Adolescent↗
PubMed1995

Testosterone-induced shortening of the storage phase of song development in birds interferes with vocal learning.

Bird song is a complex, learned behavior. Vocal learning in sparrows involves several different processes that occur in a distinct temporal pattern over the course of the first year of life. Songs are acquired without practice during a sensitive period within the first 3 months of life and rehearsal of the acquired song does not begin until 7 or 8 months of age. The function of the storage period between song acquisition and production is not known. We set out to investigate its significance by administering testosterone, known to stimulate production of adult song, to birds at 100 days of age after song acquisition was completed but some 5 months prior to normal song onset. Most testosterone-treated birds produced abnormal songs resembling those of males raised in acoustic isolation suggesting that, in sparrows, events occurring during the storage phase play a significant role in vocal learning.

Animals↗
PubMed1995

Ethnic differences in regional bone density, hip axis length, and lifestyle variables among healthy black and white men.

There are few published data on bone mass, measured by dual-energy X-ray absorptiometry (DXA), in healthy white or black men. Similarly, a recently described predictor of hip fracture among white women, hip axis length (HAL), has not been studied in men. We recruited 160 white and 34 black men, aged 23-80 years, and screened for diseases and drug exposures that adversely affect skeletal health. We measured bone mineral density (BMD) in the lumbar spine, femoral neck, and radial shaft by DXA; height and weight; skin color by reflectometry; and hip axis length both directly from DXA output and using automated software in a subsample. We also obtained historical data on education, smoking, exercise, and fractures. There were no significant black/white differences in mean weight, height, body mass index (BMI), or HAL. The black men had higher BMDs than did the white men at every site (5% for the radius, 10% for the lumbar spine, and 20% for the femoral neck). Skin pigmentation and BMD were not significantly correlated in either group (p > 0.38). Among the white men, smoking was associated with lower lumbar BMD, but there was no significant relationship between BMD and exercise frequency in either group. There was no significant ethnic difference in fracture experience. We conclude that: (1) the higher BMD in black men than in white men is not due to greater body size, (2) the lower hip fracture risk reported for black men than for white men is not due to a difference in hip axis length; (3) skin color is not related to BMD in either sex.

Absorptiometry, Photon↗
PubMed1995

Effect of the kinase inhibitor 2-aminopurine on the cell cycle stage-dependent phosphorylation state of the retinoblastoma protein.

We investigated the effect of 2-aminopurine (2-AP) on the cell cycle stage-dependent phosphorylation state of the retinoblastoma growth suppressor protein (pRB). Our results suggest that 2-AP does not affect dephosphorylation of pRB scheduled during metaphase/anaphase of mitosis, even though 2-AP-treated cells never enter metaphase or anaphase. Phosphorylation of pRB, which is important for G1 exit, appeared to be impeded by 2-AP late during G1, coincident with a slowing of G1 cell progression into S phase. The significance of these data with regard to cell cycle regulation is discussed.

2-Aminopurine↗
PubMed1995

Control and activity of type-1 serine/threonine protein phosphatase during the cell cycle.

The first part of this discourse will serve as a compendium of selected aspects of PP1 activity and control during the cell cycle. The latter sections will focus on the mammalian cell cycle dependent activity of PP1 on the negative growth regulatory product of the retinoblastoma susceptibility gene, pRB. The purpose here is to suggest one possible mechanism to explain how this phosphatase can effect cell cycle progression. An argument is made for PP1 playing an indirect role in regulating cell cycle progression by modulating the growth suppressive activity of pRB.

Animals↗
PubMed1995

Influence of temperature changes on multiple sclerosis: critical review of mechanisms and research potential.

In 1890, Uhthoff studied multiple sclerosis (MS) patients who developed amblyopia following exercise, a phenomenon later discovered to be secondary to elevated body temperature from muscular activity. Six decades later, the hot bath test and various other heating reactions (HR) began to be used diagnostically. They were essentially discontinued after 1983, being replaced by more specific and safer tests and procedures. Over 80% of MS patients develop a panoply of neurological signs during hyperthermia, 60% of which are "new" to that patient. The literature contains a number of unexplained paradoxical responses of MS patients during induced hyperthermia. These challenge the current hypothesis that, in MS, hyperthermia induces a heat-linked neuro-blockade of partially demyelinated axons. Some MS patients developed signs before temperature elevations occurred; others showed clearing of signs while temperatures were elevated or were ascending. Several MS patients improved for about 3 hours after being tested, a rebound phenomenon known as "overshoot." Conversely, other MS patients developed persistent neurological deficits after hyperthermia. The etiology of HR may be multifactorial. This includes heat itself, effects of serum calcium, blockade of ion channels, circulatory changes, heat shock proteins, and unidentified humoral substances. Research techniques are suggested to continue investigations into the enigma of HR, hopefully to widen knowledge of demyelination.

Amblyopia↗
PubMed1995

Emergence of functional circuits in ferret visual cortex visualized by optical imaging.

The emergence of functional lateral interactions in ferret visual cortex was monitored using high speed optical imaging of voltage-sensitive dye signals in brain slices. Prior to the time of eye opening, lateral activation was restricted to a narrow columnar region. During the week following eye opening, the extent of lateral propagation of activity more than doubled. Selective interruption of specific pathways in the slice, combined with pharmacological and anatomical experiments, determined that this lateral propagation was mediated by horizontal projections made within layer 2/3. These results indicate that functional horizontal interactions emerge only after axons begin branching and in parallel with, but not prior to, the refinement of orientation selectivity.

Age Factors↗
PubMed1995

Neuronal domains in developing neocortex: mechanisms of coactivation.

The mammalian neocortex consists of columnar circuits, whose development may be controlled by patterns of spontaneous activity. Columnar domains of spontaneously coactive neurons were previously described using Ca2+ imaging of slices from developing rat neocortex. We have now investigated the cellular mechanisms responsible for the coactivation of these domains. The activation starts in the center of a domain and spreads at speeds of approximately 100 microns/s. Domains occur in the presence of tetrodotoxin but are blocked by the gap junction blockers halothane and octanol. Simultaneous intracellular and optical recordings from dye-coupled cells reveal functional coupling between developing neocortical neurons. These data support the hypothesis that a neuronal domain results from the spontaneous excitation of one or a few trigger neurons that subsequently activate, either electrically or biochemically, the rest of the cells via gap junctions.

Animals↗
PubMed1995

Critical bandwidth for phase discrimination in hearing-impaired listeners.

Monaural phase discrimination was evaluated in normal-hearing and hearing-impaired listeners as a function of the frequency separation among components in three-tone complexes. The phases of the center components of 100% sinusoidal amplitude-modulated (SAM) waveforms were shifted by 90 degrees to yield quasi-frequency-modulated (QFM) waveforms that had identical long-term spectra but different envelopes and temporal fine structure. Normal-hearing listeners can distinguish QFM waveforms from SAM waveforms as long as the modulation frequency (frequency separation between components) is less than about 40% of the carrier frequency (center component). Phase discrimination performance (d') was measured as a function of modulation frequency, and critical bandwidths for phase discrimination (CBphs) were specified as the modulation frequency corresponding to a performance index (d') of 1.0. In normal-hearing ears, CBphs increased with stimulus SPL. In hearing-impaired ears, CBphs estimates were equal to or narrower than normal when comparisons were made at the same SPLs; CBphs estimates from hearing-impaired ears were broader (better) than normal only when comparisons were made at equivalent SLs. Differences between CBphs estimates in normal-hearing and hearing-impaired ears are explained by level-dependent auditory filtering and the sensation levels at which comparisons are made, without the necessity to postulate abnormal tuning in hearing-impaired ears.

Adult↗
PubMed1995

Electrode ranking of "place pitch" and speech recognition in electrical hearing.

The ability to distinguish electrical stimulation of different electrodes on the basis of "pitch or sharpness" was evaluated with an electrode ranking procedure in 14 individual users of the Nucleus cochlear implant. Prior to the electrode ranking test, absolute thresholds and maximum comfortable loudness levels were measured, and loudness balancing was accomplished across all usable electrodes. Performance on the electrode ranking task was defined in terms of d' per mm of distance between comparison electrodes. Large individual differences were found among cochlear-implant users. In subjects with good to excellent place-pitch sensitivity, the electrode ranking task was limited by a ceiling effect; however, in those with poor to moderate sensitivity d'/mm was relatively constant with spatial separation between electrodes. Place pitch was typically ordered from apical to basal electrodes, i.e., basal electrodes were judged to be higher in pitch than more apical electrodes. However, instances of reversals in place-pitch ordering were seen on some electrodes in some subjects. Instances were also seen of better electrode ranking in the apical half of the electrode array than in the basal half, and vice-versa. Analyses of the electrode ranking functions in terms of d' per stimulus indicated that, in some subjects, perfect performance was reached with as little as 0.75 mm between comparison electrodes, the minimum possible. In other subjects, perfect performance was not reached until the spatial separation between comparison electrodes was over 13 mm, more than three quarters of the entire length of the electrode array. Ten of the subjects also participated in a closed-set recognition task of intervocalic consonants. Although the maximum transmitted information for place of consonant articulation (which is based primarily on spectral speech cues) was only 34%, correlations between place-pitch sensitivity and transmitted speech information were as high as 0.71. This was surprising considering the excellent place-pitch sensitivity exhibited by some of the subjects, and may reflect limitations of the Nucleus speech coding strategy for representing spectrally coded speech information. The two prelingual subjects performed notably poorer on the speech task than the postlingual subjects, even though one of the prelingual subjects demonstrated very good place-pitch sensitivity.

Adult↗
PubMed1995

Managing the triage of GI hemorrhage as a function of stability.

The authors present a refined triage tool to assist in the identification of patients with GI hemorrhage. Criteria include orthostasis; current, active GI hemorrhage; hemoglobin under 10 g/dl or a 3 g/dl drop from a known baseline; and history of underlying organ system dysfunction.

Adult↗
PubMed1994

Selection-based learning in bird song development.

Bird song is a model system for study of the neurobiology, development, and functions of learned vocal communication signals. Research on avian song learning has been dominated by an instructive model of learning--the sensorimotor model. Developmental plasticity is assumed to be based on the incorporation of novel material into the song repertoire. Experimental evidence now indicates an alternative form of plasticity operating in harmony with sensorimotor learning, based on principles of selection, rather than instruction. Song dialects, a common consequence of vocal learning, can be achieved by overproduction of previously memorized songs and selective attrition of those that fail to match the dialect of interacting males. These distinct processes of learning have important implications for study of the neural substrates underlying song production and perception and for efforts to interpret patterns of geographic variation in song.

Aging↗
PubMed1994

Reversal of vertebral deformities in osteoporosis: measurement error or "rebound"?

Digitized morphometry of vertebral bodies on lateral spine films is used to identify and quantify vertebral deformities or fractures. One problem associated with this method is the phenomenon of "disappearing fractures," which results from the apparent increase in vertebral body heights of previously deformed vertebrae on subsequent radiographs. These have been considered biologically implausible and therefore a result of measurement error. Measurement error is unlikely to be unidirectional, so that a proportion of fractures identified by morphometry is also the result of measurement error. Since some vertebral deformities are real events, some disappearances of deformities detected by morphometry may be real events. In this report, we examine the data from our clinical trial of sodium fluoride in spinal osteoporosis to assess critically the plausibility of two hypotheses: (1) The "rebound" phenomenon results from measurement error. If this is the case, then some fractures of the same magnitude as the rebound must also represent measurement error. (2) Some deformed vertebrae in fact rebound toward their original shape and size, displaying an elastic response to deformation. If this occurs, then some vertebral deformities are transient events, not true fractures. We conclude that the variability inherent in morphometric data obtained from serial spine x-rays results in both disappearing fractures and a high false positive fracture rate. The use of more stringent criteria for defining significant deformities, or true fractures, will minimize these problems. We cannot exclude the second hypothesis, that some vertebral deformities may be transient events, but this needs further study.

Aged↗
PubMed1994

Reference data for bone mass, calciotropic hormones, and biochemical markers of bone remodeling in older (55-75) postmenopausal white and black women.

From a random sample of our institution's health maintenance organization (HMO), we recruited 250 white women and 112 black women, aged 55-75, all of whom were 10 or more years postmenospause with minimal estrogen exposure and free of osteoporosis, other metabolic bone disease, and medical, surgical, or therapeutic situations that may influence bone loss. Bone mass was measured in the radius, spine, and femur by DXA and in L1 by QCT. Serum samples were analyzed for parathyroid hormone, calcidiol, calcitriol, osteocalcin, and bone alkaline phosphatase and urine samples analyzed for creatinine, calcium, and hydroxyproline. Mean Z score, based on published reference data for forearm and femoral neck BMD in the white women, was not significantly different from zero, but mean Z score at the lumbar spine was 0.6 (p < 0.001), 17.2% of the individual values being > 2.0. In normal white women (BMI < 27.3, n = 143), Z score was still > 2.0 in 10.3%, suggesting that the upper bound of the published reference interval may be too low. After adjustment for body mass index, BMD was greater in the forearm (9.8%), spine (8.7%), and femoral neck (14.7%) in black women (p < 0.001 at all sites). At L1, adjusted BMC in the black women was 37.4% greater than in the white women (p < 0.001). Serum calcidiol was significantly lower and serum PTH and calcitriol significantly higher in the black women. Despite this, biochemical markers of bone resorption and formation were significantly lower in the black women. We conclude that skeletally healthy older black women have a greater bone mass and lower rates of bone remodeling than a comparable group of white women. These data can serve as reference intervals for the variables measured.

Aged↗
PubMed1994

Comparison of radiographic absorptiometry with dual-energy x-ray absorptiometry and quantitative computed tomography in normal older white and black women.

Bone mineral density (BMD) of the phalanges of the hand was measured by the technique of radiographic absorptiometry (RA) in 199 older postmenopausal women previously determined to have normal BMD by dual-energy x-ray absorptiometry (DXA) and quantitative computed tomography (QCT). The average age of the women was 66.8 +/- 4.9 years, and they were 19.9 +/- 6.7 years postmenopause. In the 54 black women, phalangeal BMD was 11.7% greater than in the 145 white women, a difference comparable to that found using DXA at the radial midshaft, the lumbar spine, and femoral neck. A correlation matrix comparing BMD measured by RA to BMD measured by DXA and QCT indicates that, in general, RA was related to the various DXA and QCT measurement sites as well as these sites were related to each other. When results for RA, DXA, and QCT obtained in our cohort of older women were compared to available reference data for peak adult bone mass, the average difference (SD units) from peak value was greatest for RA (-1.77 radius, -1.24 spine, -2.13 femoral neck, -2.34 QCT spine, and -2.71 phalanges). We conclude that RA is an acceptable measure of phalangeal BMD and that the data in our cohort can serve as reference data for older white and black women aged 55-75 years. Once the ability of RA to predict future fracture occurrence has been demonstrated, it could be rapidly deployed as a low-cost, widely available bone mass measurement technique.

Absorptiometry, Photon↗
PubMed1994

Limitations on arteriovenous cooling of the blood supply to the human brain.

Arteriovenous heat transfer (AVHT) is a thermoregulatory phenomenon which enhances tolerance to thermal stress in a variety of animals. Several authors have speculated that human responses to thermal stress reflect AVHT in the head and neck, even though primates lack the specialized vascular arrangements which characterize AVHT in other animals. We modeled heat transfer based on the anatomical relationships and blood flows for the carotid artery and associated venous channels in the human neck and cavernous sinus. Heat transfer rate was predicted using the "effectiveness-number of transfer units" method for heat exchanger analysis. Modeling showed that AVHT is critically dependent upon (1) heat exchanger effectiveness and (2) arteriovenous inlet temperature difference. Predicted heat exchanger effectiveness is less than 5.5% for the neck and 0.3% for the cavernous sinus. These very low values reflect both the small arteriovenous interface for heat exchange and the high flow rate in the carotid artery. In addition, humans lack the strong venous temperature depression required to drive heat exchange; both the cavernous sinus and the internal jugular vein carry a large proportion of venous blood warmed by its passage through the brain as well as a small contribution from the face and scalp, whose temperature varies with environmental conditions. Under the most optimistic set of assumptions, carotid artery temperature would be lowered by less than 0.1 degrees C during its passage from the aorta to the base of the brain. Physiologically significant cooling of the blood supply to the brain cannot occur in the absence of a suitably scaled site specialized for heat exchange.

Blood Flow Velocity↗
PubMed1994

Level-dependent critical bandwidth for phase discrimination.

Monaural phase discrimination was evaluated at 1000 Hz in six normal-hearing listeners as a function of the frequency difference between components in three-tone complexes at 40, 60, 80, and 100 dB SPL. The phase of the center component of 100% sinusoidally amplitude-modulated (SAM) waveforms was shifted by 90 degrees to produce quasi-frequency-modulated (QFM) waveforms that had identical long-term power spectra to the SAM waveforms but with different amplitude envelopes and temporal fine structure. At low modulation frequencies, where spectral components were close together and presumably all well within a single auditory filter, normal-hearing listeners could easily discriminate QFM from SAM waveforms. As modulation frequency increased, a point was reached where listeners could no longer distinguish QFM from SAM waveforms, referred to here as the critical bandwidth for phase discrimination (CBphs). Discrimination performance (d') was measured as a function of modulation frequency to yield a psychometric function for phase discrimination. From the psychometric function, CBphs was defined as the modulation frequency corresponding to d' = 1.0. At a carrier frequency of 1000 Hz, CBphs increased with level between 40 and 80 dB SPL according to the relation: CBphs = 34.I(0.136). Above 80 dB SPL, very little change in CBphs with level was seen. The increase with level of the geometric mean CBphs was predicted from level-dependent auditory filter slopes inferred from forward-masked tuning curves, as was the tendency to reach an asymptote above 80 dB SPL. Comparisons with previous work indicate that CBphs values from the best performing subjects were well within the audibility region for cubic difference tones. It is proposed that internally generated cubic difference tones interact with externally generated acoustic components, both limited by a level-dependent auditory filter, to produce an internal excitation envelope that is the basis for discriminating between SAM and QFM waveforms. It is also suggested that individual differences at low levels may be due to internal phase ambiguities.

Attention↗