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Biomedical subjects

D A Nelson

Publications and source records attributed to D A Nelson.

At least 127 records · Page 7Linked to original sources

Ion channels and insulin secretion.

We review the role of ion channels in regulating insulin secretion from pancreatic beta-cells. By controlling ion permeability, ion channels at the membrane play a major role in regulating both electrical activity and signal transduction in the beta-cell. A proximal step in the cascade of events required for stimulus-secretion coupling is the closure of ATP-sensitive K+ channels, resulting in cell depolarization. Of particular relevance is the finding that this channel is directly regulated by a metabolite of glucose, which is the primary insulin secretagogue. In addition, this channel, or a closely associated protein, contains the sulfonylurea-binding site. Another K+ channel, the Ca2(+)-activated K+ channel, may be involved in cell repolarization to create homeostasis. Voltage-dependent Ca2+ channels are activated by cell depolarization and regulate Ca2+ influx into the cell. By controlling cytosolic free-Ca2+ levels ([Ca2+]i), these channels play an important role in transducing the initial stimulus to the effector systems that modulate insulin secretion. The link between a rise in [Ca2+]i and the terminal event of exocytosis is the least-understood aspect of stimulus-secretion coupling. However, phosphorylation studies have identified substrate proteins that may correspond to those involved in smooth muscle contraction, suggesting an analogy in the processes of stimulus secretion and excitation contraction. The advent of new methodology, particularly the patch-clamp technique, has fostered a more detailed characterization of the beta-cell ion channels. Furthermore, biochemical and molecular approaches developed for the structural analysis of ion channels in other tissues can now be applied to the isolation and characterization of the beta-cell ion channels. This is of particular significance because there appear to be tissue-specific variations in the different types of ion channels. Given the importance of ion channels in cell physiology, a knowledge of the structure and properties of these channels in the beta-cell is required for understanding the abnormalities of insulin secretion that occur in non-insulin-dependent diabetes mellitus. Ultimately, these studies should also provide new therapeutic approaches to the treatment of this disease.

Animals↗

The biology of myelopoiesis.

The myelopoietic system includes the hematopoietic cells derived from a common hematopoietic stem cell that includes erythroid, granulocytic, monocytic, and megakaryocytic lineages. The contributions of molecular genetic techniques to hematopoiesis in the past 5 years have led to quantum leaps in our understanding, but there is room for further research. Current concepts of stem cells and the hematopoietic microenvironment are discussed, as are committed progenitor cells and hematopoietic growth factors, particularly those concerning the neutrophilic, monocytic, and erythroid systems.

Animals↗

Categorical perception of a natural stimulus continuum: birdsong.

A fundamental issue in perception and communication is how continuously varying stimuli are partitioned into discrete categories. In swamp sparrow songs, note duration is a critical feature distinguishing two note categories with different roles in song construction. Pairs of songs with initial notes from different categories contrast more in their effects on territorial males than song pairs with initial notes differing by the same amount but taken from within one note category. The results indicate categorical perception by wild swamp sparrows.

Animal Communication↗

Morphologic and cytochemical characteristics of acute promyelocytic leukemia.

The existence of two distinct subtypes of acute promyelocytic leukemia was confirmed and characterized based on morphologic features of leukemic cells in a series of 63 patients studied by the Cancer and Leukemia Group B (CALGB). Seventeen patients (27%) had microgranular leukemic cells (M3V), and 46 patients (73%) had hypergranular leukemic cells (M3). These patient cohorts were studied for other laboratory and clinical features. Leukemic cells from M3V patients stained less frequently than leukemic cells from M3 patients for myeloperoxidase (median, 93% vs. 99%; P = .006), periodic acid-Schiff (median, 57% vs. 92%; P = .0001), ASD-chloroacetate esterase (median, 45% vs. 87%; P less than .0001), and alpha-naphthyl acetate esterase (0% vs. 37%; P = .0003). Patients with M3V had a higher platelet count (median, 50 vs. 30 x 10(9)/L; P = .01) and tended to have a higher leukocyte count (median, 7.4 vs. 2.2 x 10(9)/L; P = .06) than M3 patients. The patients with M3V morphology were more likely to be nonwhite (29% vs. 7%; P = .03), female (71% vs. 37%; P = .02), and to be infected at the time of presentation (71% vs. 35%; P = .02). No differences in the frequency of the t(15;17) karyotype or the immunophenotypic expression of the leukemic cells were noted in the two morphologic subtypes of acute promyelocytic leukemia. Fewer patients with M3V tended to enter complete remission (65% vs. 80%; P = .20), but no significant differences were found in the duration of complete remission (P = .81; 1 year rate, 50% vs. 85%), or probability of survival (P = .67; 1 year rate, 49% vs. 68%).

Adolescent↗

Song frequency as a cue for recognition of species and individuals in the field sparrow (Spizella pusilla).

Estimate the amount of frequency variation that affected individual and species recognition by song in territorial male field sparrows with field playbacks of neighbors' songs lowered in frequency in 6 increments between 324 and 1296 Hz. Males gave strong responses to neighbors' songs that had been lowered by about 400 Hz, which is about 11% of the mean midfrequency in field sparrow song. Territorial responses were eliminated when neighbors' songs were lowered by more than about 900 Hz. Thus, there is a fairly narrow range of frequencies within which field sparrow songs can vary while functioning in communication. Ss' responses appear to be constrained by the normal range of song frequency variation within the species, but the range of variability within songs of individuals did not influence the degree of frequency shift required to render neighbors' songs unfamiliar.

Animal Communication↗

Auditory time constants for off-frequency forward masking in normal-hearing and hearing-impaired listeners.

Previous research has shown that frequency-specific estimates of auditory time constants for recovery from short-term adaptation can be made using a fixed-probe forward-masking procedure (Nelson & Freyman, 1987) if the masker and the probe stimuli are at the same frequency. This study examines the validity of time-constant estimates for off-frequency forward-masking conditions in which the masker frequency is below (900 Hz) or above (1100 Hz) the probe frequency (1000 Hz). Fixed-probe-level temporal masking functions were obtained from four normal-hearing and four hearing-impaired listeners. Auditory time constants were estimated with iterative least-squares procedures to derive parameter values for an exponential model of recovery from forward masking. After appropriate corrections were made for attenuation to the maskers provided by the auditory filter centered at the probe frequency, recovery from forward masking produced by either off-frequency or on-frequency maskers could be described by a single time constant. That time constant was around 50 ms in normal-hearing listeners and was larger in those hearing-impaired listeners who demonstrated moderate hearing loss at the probe frequency.

Auditory Fatigue↗

Temporal overshoot in simultaneous-masked psychophysical tuning curves from normal and hearing-impaired listeners.

Simultaneous-masked psychophysical tuning curves (PTCs) were obtained from normal-hearing and sensorineural hearing-impaired listeners. The 20-ms signal was presented at the onset or at the temporal center of the 400-ms masker. For the normal-hearing listeners, as shown previously [S. P. Bacon and B. C. J. Moore, J. Acoust. Soc. Am. 80, 1638-1645 (1986)], the PTCs were sharper on the high-frequency side for a signal in the temporal center of the masker. For the hearing-impaired listeners, however, the shape of the PTC was virtually independent of the temporal position of the signal. These data suggest that the mechanisms responsible for sharpening the PTC with time in normal-hearing listeners are ineffective in listeners with moderate-to-severe sensorineural hearing loss.

Attention↗

Speech pathology in giant cell arteritis. Review and case report.

This paper contains a review of the signs and symptoms of giant cell arteritis, especially speech and respiratory manifestations of the disease, which are demonstrated by a new case history. An elderly woman presented with speech that was falsetto, breathy, and marked by downward pitch breaks and phonation breaks. In addition, she had visual loss, headache, edema along the scalp and pharyngeal arteries, polymyalgia rheumatica, elevation of Westergren erythrocyte sedimentation rates, and positive arterial biopsy results. Her speech disorder recurred during an exacerbation. A vascular mechanism is proposed to explain her unusual speech, acute recurrence, and rapid recovery. This explanation (reversible ischemia of the laryngeal musculature) has been proposed by other authors in previous studies.

Aged↗

Distortion product emissions and sensorineural hearing loss.

Distortion product emissions (DPEs) are intimately linked to normal outer hair cell function. Outer hair cell function is itself intimately linked with normal auditory thresholds. We sought to correlate frequency-specific DPE measurements with auditory thresholds, in seven frequency regions from 700 Hz to 6 kHz, in each of 21 ears. Eleven of these ears had thresholds below 25 dB SPL at every test frequency, whereas 10 ears demonstrated some degree of purely sensorineural hearing loss. An analysis of the correlation between DPE measurements and sensory thresholds suggests that DPE measures can predict frequency-specific auditory thresholds to within 10 dB over a range of sensory thresholds from 0 dB SPL to 60 dB SPL. Distortion product emissions promise to provide an objective, non-invasive measure of sensory thresholds. The clinical value of DPE measurement is enhanced by that fact that it is brief and requires minimal subject participation. A clinical test based on the DPE measurement will not displace conventional audiometry or auditory brain stem response measurement. It promises to provide new information about cochlear function to both the clinician and auditory physiologist.

Acoustic Stimulation↗

Cochlear implant hearing performance at the University of Minnesota.

The hearing performance of six post-lingually deaf adults implanted with the Nucleus 22-channel device are presented. All patients achieved measurable open set speech recognition with implant alone. The best hearing performance was achieved with a combination of lipreading and cochlear implant. For this condition our group achieved an average open set speech discrimination score of 85% (CID sentences) and an average speech tracking rate of 70 words per minute. We attribute the success of our group to careful pre-operative selection, including attention to candidate motivation toward hearing rehabilitation.

Adult↗

Histone acetylation in chicken erythrocytes. Rates of acetylation and evidence that histones in both active and potentially active chromatin are rapidly modified.

Of the modifiable histone lysine sites, 2-4% participate in dynamic acetylation in chicken erythrocytes, suggesting the involvement of no more than 1-2% of the total genome. The rates and chromatin locality of this dynamic acetylation were studied in both chicken mature and immature red blood cells. In mature erythrocytes, two rates of acetylation of radiolabelled, monoacetylated H4 are observed, with half-lives of approximately 12 and approximately 300 min. In contrast, only one rate with a half-life (t1/2) of 12 min is observed in immature cells, and further experiments rule out the possibility of a slow rate of acetylation (with a t1/2 of approximately 300 min) for any form of H4 in this cell type. The simplest interpretation of these quantitative results, taken together with the behaviour of H3, H2B and H4 observed on the fluorograms used for rate analysis, is that a portion of the rapidly acetylated histone is converted to a more slowly acetylated form during erythrocyte maturation. The transcriptionally active adult beta-globin and H5 nucleohistone, which are presumably converted to potentially active chromatin during the maturation process, remain of the rapidly acetylated form in the mature cell.

Acetylation↗

Histone acetylation in chicken erythrocytes. Rates of deacetylation in immature and mature red blood cells.

We analysed the rates of histone deacetylation in chicken mature and immature red blood cells. A multiplicity of deacetylation rates was observed for the histones and these rates may be subdivided into two major categories based on the extent of histone acetylation. In one set of experiments, cells were labelled with [3H]acetate in the presence of the deacetylase inhibitor n-butyrate, thereby accumulating radiolabel in the hyperacetylated forms of the histone. These hyperacetylated forms are deacetylated rapidly. [3H]Acetate-labelled tetra-acetylated H4 (H4Ac4) in mature cells was deacetylated with an initial half-life (t1/2) of approximately 5 min (time required for the removal of one-half of the labelled acetyl groups). In immature cells, all [3H]acetate-labelled H4Ac4 was deacetylated with a t1/2 of approximately 5 min. Erythrocytes were also labelled with [3H]acetate for extended periods in the absence of the deacetylase inhibitor. During this period, radiolabel accumulated predominantly in the mono- and di-acetylated forms of the histone. Using this protocol, the rate of deacetylation of H4Ac1 was observed to be approximately 145 min for mature cells, and approximately 90 min for immature cells, demonstrating that the less extensively acetylated histone is deacetylated slowly. These results are discussed in the context of the rates of histone acetylation in chicken red blood cells described in the companion paper [Zhang & Nelson (1988) Biochem. J. 250, 233-240].

Acetylation↗

Dangers from methylprednisolone acetate therapy by intraspinal injection.

Clinical trials first began in 1960 with methylprednisolone acetate (Depo-Medrol) administered intrathecally, in an attempt to treat both disk disease and multiple sclerosis. After a few reports of salubrious results, there began an outpouring of contradictory data, which continues in 1988. During this time span, researchers who cautiously tested the different theses of improvement began to publish serious warnings of many complications. For ten years prior to the intraspinal use of methylprednisolone acetate, basic scientists in anesthesiology and neurochemistry had published the following facts: (1) Methylprednisolone acetate's content of polyethylene glycol raises the risks of using it near the central nervous system. (2) Deleterious effects follow the use of glycols when they are placed into or near the neuraxis. (3) Methylprednisolone acetate contains approximately 30 mg of polyethylene glycol per milliliter. (4) When that glycol, which is both alcohol and detergent, is injected intraspinally, sterile meningitis, arachnoiditis, or pachymeningitis will occur. It has also been recognized since the 1960s that the epidural space is not wholly separate from the subdural and/or subarachnoid space. Many thousands of arachnoid villi subtend all the membranes from the intrathecal space, and many of these end in the large epidural veins. Therefore, the various spaces and membranes are not only contiguous, but continuous. It follows that an injection of methylprednisolone acetate into the epidural space does not guarantee that it will remain isolated there. Finally, the inadvertency of injections by the epidural route occurs with the following frequency: 40% of injections can be inadvertently made into interspinous ligaments, and 2.5% into the subarachnoid space.

Demyelinating Diseases↗