Effect of heavy metals on bay scallops, surf clams, and blue mussels in acute and long-term exposures.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
D A Nelson
Publications and source records attributed to D A Nelson.
Morphologic and cytochemical characterization of adult lymphoid leukemias which express myeloid antigen.
Cancer and Leukemia Group B demonstrated that adults with acute lymphoid leukemia (ALL) possessing blast cells with myeloid antigens (My+ALL), as identified by monoclonal antibodies against CD13 and CD33, have a worse prognosis than those lacking myeloid antigens (My-ALL). Consequently, we further studied this group of adults with ALL to determine if these immunological groups could be distinguished by morphological and cytochemical criteria. Bone marrow films were classified according to French-American-British Co-operative Group Criteria, assessed for myelodysplasia, and examined for blasts with azurophilic granules. More cases of My+ALL had L2 morphology than did My-ALL (68% vs. 49%, p = 0.04), and more cases of My+ALL were positive for acid alpha-naphthyl acetate esterase (61% vs. 31%, p = 0.03). The presence of myelodysplastic changes was not significantly different in My+ALL (13%) as compared to My-ALL (5%), but more cases of My+ALL had unusual blasts (monocytoid features and cytoplasmic buds) than did My-ALL (19% vs. 0%, p less than 0.01). In addition, more cases of My+ALL had greater than 5% of the blasts with azurophilic granules (42% vs. 13%, p = 0.01). In the My+ALL group the presence of azurophilic granules was associated with a longer median survival (13.5 months vs. 1.5 months, p less than 0.01). We conclude that My+ALL can be suspected when cases possess L2 morphology, unusual blasts, positive staining for acid alpha-naphthyl acetate esterase, and greater than 5% azurophilic granules. In addition, the poor risk group (My+ALL) can be further subdivided into better and poorer risk subgroups based on the presence of azurophilic granules.
Adolescent↗
Bone mass, skin color and body size among black and white women.
We investigated the relationship between bone mass and two variables, skin color and body size, that may contribute to the higher prevalence of osteoporosis among white than among black populations. From a sample of 36 black and 99 white women were obtained measurements of height, weight, skin color (Photovolt 670 reflectometer) and radial bone mineral content (BMC) and bone width (BW) (single photon absorptiometry). There was no significant correlation between skin reflectance and age-adjusted BMC in either population. Multiple regression models of BMC and BMC/BW on age, weight/height and skin reflectance yielded significant correlations ranging from 0.62 to 0.77, but the partial coefficients for skin reflectance were not significant. BMC and age were negatively correlated in both groups, with a significantly steeper slope for the whites. Weight was positively correlated with BMC in both populations, but differences in weight did not explain the differences in bone mass between the blacks and whites.
Adult↗
Osteoporosis as a community health problem: lessons learned from studying hypertension.
Explore the source record for details and available documents.
Blood Pressure Determination↗
Chicken erythrocyte beta-globin chromatin: enhanced solubility is a direct consequence of induced histone hyperacetylation.
Chicken immature red blood cells were incubated for 1 hour in Swim's medium containing 3H-acetate and 10 mM n-butyrate. During the incubation period, the small percentage of dynamically acetylated and deacetylated histone is radiolabeled and hyperacetylated. A second effect of the n-butyrate incubation is to shift a small subset of nucleohistone into a soluble form. This chromatin is predominantly polynucleosome size (approximately dimer to pentamer) and can be separated from soluble mononucleosomes by 5-30% sucrose gradient centrifugation. The soluble polynucleosomes are 25-30 fold enriched for adult beta-globin (beta A) DNA and contain the hyperacetylated histones. We have tested whether histone hyperacetylation is responsible for the enhanced beta-globin chromatin solubility by in vitro deacetylation of the soluble chromatin histones. This procedure converts the beta-globin polynucleosomes to an insoluble form, demonstrating that histone hyperacetylation is in fact directly responsible for the increased solubility of the beta A chromatin.
Acetylation↗
Polyamines inhibit the yeast histone deacetylase.
n-Butyrate inhibits the histone deacetylase from higher cells, but has little effect on the enzyme activity in Saccharomyces cerevisiae. Spermine and spermidine were therefore tested as potential yeast deacetylase inhibitors and found to inhibit fully the enzyme at 2 and 5 mM, respectively. The utility of these inhibitors was demonstrated by showing that 2 mM spermine substantially increased the incorporation of [3H]acetate into histone in a yeast nuclear acetyltransferase assay.
Acetates↗
Clinical importance of myeloid antigen expression in adult acute lymphoblastic leukemia.
To determine the clinical importance of immunophenotypes in adult acute lymphoblastic leukemia (ALL), we prospectively studied 76 patients with this condition. Before treatment, lymphoblasts were tested for reactivity with monoclonal antibodies to B-cell, T-cell, and myeloid (My) antigens. Unexpectedly, myeloid antigens (MCS-2 or MY9) were identified in 25 patients (33 percent), usually in conjunction with B-cell or T-cell antigens. Among My+ patients, 15 (60 percent) expressed B-cell antigens (B+T-My+); all 6 tested had rearranged immunoglobulin genes. Five patients (20 percent) expressed T-cell antigens (B-T+My+), and one My+ patient expressed both B-cell and T-cell antigens. Only myeloid antigens (B-T-My+) were expressed in four patients (16 percent); three who were tested had germ-line immunoglobulin and T-cell-receptor gene configurations. Although no significant differences in presenting clinical features were found, My+ patients had fewer complete remissions than My- patients (35 vs. 76 percent, P less than 0.01). No differences in response or survival were observed between My+ and My- patients expressing T-cell antigens. However, among those expressing B-cell antigens, My+ patients had fewer complete remissions (29 vs. 71 percent, P = 0.02) and shorter survival (P = 0.03; median, 8.1 vs. greater than 26 months). These findings indicate that expression of myeloid antigen identifies a high-risk group of patients with adult ALL for whom alternative forms of treatment should be investigated.
Adult↗
Frequency discrimination of short- versus long-duration tones by normal and hearing-impaired listeners.
This investigation explored the effects of stimulus level on the frequency discrimination of long- and short-duration pure tones by 5 subjects with normal hearing and 7 with sensorineural hearing impairment. Frequency difference limens (DLs) were obtained as a function of signal intensity for 5-ms and 300-ms tones at 500, 1000, and 2000 Hz. The performance of most of the hearing-impaired subjects was poorer than normal for 300-ms tones, but not for 5-ms tones. This result was relatively independent of the stimulus sensation levels at which the data were compared. However, the current results also show an unexpected dependence of the frequency DL on the sensation level of short-duration tones. In several normal-hearing subjects, frequency discrimination performance for these short tones is poorer at moderately high levels than at low levels.
Adult↗
Temporal resolution in sensorineural hearing-impaired listeners.
Temporal masking curves were obtained from 12 normal-hearing and 16 hearing-impaired listeners using 200-ms, 1000-Hz pure-tone maskers and 20-ms, 1000-Hz fixed-level probe tones. For the delay times used here (greater than 40 ms), temporal masking curves obtained from both groups can be well described by an exponential function with a single level-independent time constant for each listener. Normal-hearing listeners demonstrated time constants that ranged between 37 and 67 ms, with a mean of 50 ms. Most hearing-impaired listeners, with significant hearing loss at the probe frequency, demonstrated longer time constants (range 58-114 ms) than those obtained from normal-hearing listeners. Time constants were found to grow exponentially with hearing loss according to the function tau = 52e0.011(HL), when the slope of the growth of masking is unity. The longest individual time constant was larger than normal by a factor of 2.3 for a hearing loss of 52 dB. The steep slopes of the growth of masking functions typically observed at long delay times in hearing-impaired listeners' data appear to be a direct result of longer time constants. When iterative fitting procedures included a slope parameter, the slopes of the growth of masking from normal-hearing listeners varied around unity, while those from hearing-impaired listeners tended to be less (flatter) than normal. Predictions from the results of these fixed-probe-level experiments are consistent with the results of previous fixed-masker-level experiments, and they indicate that deficiencies in the ability to detect sequential stimuli should be considerable in hearing-impaired listeners, partially because of extended time constants, but mostly because forward masking involves a recovery process that depends upon the sensory response evoked by the masking stimulus. Large sensitivity losses reduce the sensory response to high SPL maskers so that the recovery process is slower, much like the recovery process for low-level stimuli in normal-hearing listeners.
Female↗
Song syllable discrimination by song sparrows (Melospiza melodia).
A habituation test paradigm was used to examine the responses of free-living territorial adult male song sparrows (Melospiza melodia) to a range of synthetic songs. The three-phrased test songs differed from one another in having either conspecific or heterospecific (swamp sparrow, M. georgiana) syllables, or silence, in the second phrase. Subjects were exposed to repeated presentations of one song type until their approach distance to a loudspeaker increased. In one experiment, birds were habituated with a song consisting of three phrases of song sparrow syllables and then tested for generalization to either novel song sparrow syllables in the second phrase, swamp sparrow syllables, or silence. Birds discriminated between song sparrow syllables on two response measures, and between song sparrow and swamp sparrow syllables on one measure. In a second experiment, after habituation to a song with swamp sparrow syllables in the second phrase, birds did not generalize to novel song sparrow syllables, but they did generalize to novel swamp sparrow syllables. Thus song sparrows make finer distinctions among conspecific syllable variants than with alien syllables. The results further suggest that subtle species-specific differences in note structure within syllables are discriminated by song sparrows and potentially provide an adequate basis for individual recognition by song.
Animals↗
Histone acetylation in chicken erythrocytes. Estimation of the percentage of sites actively modified.
Within the N-terminal regions of the DNA-bound histone, 26 lysine residues per nucleosome may be acetylated and deacetylated. In the present paper the percentage of these residues actively acetylated and deacetylated in chicken erythrocytes was measured. This percentage is estimated as 3.7% in chicken immature, and 2.1% in chicken mature, erythrocytes. In metabolically active, dividing, cells one would predict that, after a few generations, each site would at some point in time be modified. We conclude that, in the relatively inactive immature chicken erythrocyte, no more than 1-2% of the genome is composed of dynamically acetylated and deacetylated histone, this percentage decreasing with cell maturity. The active histone acetylation and deacetylation may be confined to transcriptionally active or potentially active erythrocyte domains.
Acetates↗
A novel yeast histone deacetylase: partial characterization and development of an activity assay.
We have characterized a histone deacetylase activity associated with yeast nuclei. An unusual feature of the deacetylase is that it is not inhibited by the short-chain fatty acids n-butyrate and propionate. These short-chain fatty acids are typically potent inhibitors of histone deacetylases in eukaryotic systems. The deacetylase(s) were detected by monitoring the levels of acetylation of yeast histones during incubation of isolated yeast nuclei. The activity was optimal at 37 degrees C and at 0.1 M NaCl. The enzyme did not require divalent cations and was inhibited by Zn2+ and Cu2+. A simple activity assay was developed using as substrate, [3H]acetate-labeled histone in chicken erythrocyte nuclei. This assay was used to demonstrate that the deacetylase(s) can be extracted from yeast nuclei with 0.5 M NaCl. A gel electrophoretic analysis of the deacetylated chicken histones verified that the solubilization of incorporated radiolabel was a result of histone deacetylation, not an artifact of histone degradation by yeast proteinases.
Amidohydrolases↗
The beta-globin domain in immature chicken erythrocytes: enhanced solubility is coincident with histone hyperacetylation.
A 60 minute exposure of chicken immature erythrocytes to n-butyrate shifts actively acetylated and deacetylated histones to hypermodified forms. Micrococcal nuclease digestion of nuclei from n-butyrate treated cells and subsequent fractionation of the chromatin releases 40-45% of the adult beta-globin (beta A) nucleohistone into a soluble fraction. This is an eleven fold enrichment over the soluble chromatin from untreated cells (Ferenz and Nelson (1985) Nucleic Acids Res. 13, 1977-1995). The enhanced beta A chromatin solubility and induced histone hyperacetylation are coincident. Removal of n-butyrate from the cell incubation medium allows rapid histone deacetylation and a striking reduction in beta A chromatin solubility. Chromatin from cells incubated in the absence of n-butyrate, or in medium containing 10 mM NaCl or 2% dimethylsulfoxide, does not exhibit histone hyperacetylation, or the acquired solubility of beta A chromatin. We show that the H4 histone co-isolated with the beta A DNA is in a hyperacetylated state and present evidence that the n-butyrate incubation increases the solubility of both coding and noncoding chromatin regions in the beta-globin domain.
Acetylation↗
Frequency discrimination as a function of tonal duration and excitation-pattern slopes in normal and hearing-impaired listeners.
Frequency difference limens were determined as a function of stimulus duration in five normal-hearing and seven hearing-impaired subjects. The frequency DL duration functions obtained from normal-hearing subjects were similar to those reported by Liang and Chistovich [Sov. Phys. Acoust. 6, 75-80 (1961)]. As duration increased, the DL's improved rapidly over a range of short durations, improved more gradually over a middle range of durations, and reached an asymptote around 200 ms. The functions obtained from the hearing-impaired subjects were similar to those from normal subjects over the middle and longer duration, but did not display the rapid changes at short durations. The paper examines the ability of a variation of Zwicker's excitation-pattern model of frequency discrimination to explain these duration effects. Most, although not all, of the effects can be adequately explained by the model.
Adult↗
Psychometric functions for frequency discrimination from listeners with sensorineural hearing loss.
Psychometric functions for pulsed pure-tone frequency discrimination were obtained from hearing-impaired listeners at frequencies with normal hearing and at frequencies with mild or moderate hearing losses. The general form of psychometric functions at hearing-impaired frequencies was found to be the same as at normal-hearing frequencies, i.e.,d' was linear with the frequency difference between tones, in Hz. For all but one psychometric function, the addition of an intercept term to the fitting equation did not account for significantly more variance than did the slope term alone. Therefore, it was concluded that psychometric functions for frequency discrimination can be adequately described with only one parameter: the slope of the psychometric function. Deficits in discrimination at hearing-loss frequencies were manifested by more gradual slopes of psychometric functions. Procedures for normalizing psychometric functions are presented, which facilitate comparisons of normal and impaired frequency discrimination data across studies and frequencies. Comparisons of dlf's (difference limen for frequency) obtained with adaptive and fixed procedures show a bias toward larger dlf's with adaptive procedures, but only at higher frequencies. A discussion of equal-interval and equal-ratio adaptive stepping rules indicates that an equal-ratio rule may be preferable.
Auditory Threshold↗
Use of surface marker analysis to predict outcome of adult acute myeloblastic leukemia.
In order to investigate the clinical significance of surface antigen analysis in acute myeloblastic leukemia (AML), the blasts from 196 patients with AML were analyzed prospectively with a panel of 16 monoclonal antibodies. The antibodies were selected to identify differentiation-associated antigens of either the myeloid lineage (MY9, PM-81, AML-2-23, MY7, MCS-1, MY8, Mo1, MY1, MY4, Mo2), T cell lineage (T101, T11), B cell lineage (B1, B4) or multiple lineages [J5 (CALLA), HLA-DR]. Independent morphological review and classification by French-American-British (FAB) criteria was performed in 161 of the 196 cases. One or more myeloid surface antigens were detected on the blasts of 195 cases, while B and T cell markers were detected on 0% to 2% of cases. When both blood and marrow samples were studied on the same patient, very few differences were noted between the antigenic profiles of the paired specimens. The frequency of expression of individual myeloid antigens ranged from 91% (PM-81) to 29% (Mo2). Expression of individual antigens was found to correlate significantly with several clinical parameters including FAB classification, cytochemical staining for alpha naphthyl acetate esterase, leukocyte count, and the presence of extramedullary disease at presentation. Two myeloid antigens (MY4 and MY7) predicted for a low rate of complete remission (CR) to standard induction chemotherapy. MY4+ cases (37% of the total population) had a CR rate of 53%, while M4- cases had a CR rate of 69% (P = .03). MY7+ cases (57% of the total population) had a CR rate of 55% while MY7- cases had a CR rate of 73% (P = .01). Neither MY4 nor MY7 antigen expression was correlated with patient age. Paired combinations of antigens were also examined. The [MY4- MY7-] phenotype was exhibited by 32% of all cases and was associated with an 82% CR rate while the CR rate of all other cases was 54% (P = .001). The expression of three antigens (HLA-DR, MY8, Mo1) was associated with a decreased continuous complete remission (P less than .05, median follow-up time of 19 months). Expression of MY8 antigen was also associated with decreased survival (P = .03). These results confirm earlier reports of antigenic heterogeneity in AML, and indicate that immunologically defined subgroups of AML patients which are of potential clinical significance can be identified.
Antibodies, Monoclonal↗
N-Butyrate incubation of immature chicken erythrocytes preferentially enhances the solubility of beta A chromatin.
The solubility of adult beta-globin chromatin (beta A chromatin) from immature chicken red blood cells can be controlled by the presence or absence of n-butyrate in a cell incubation medium. In the absence of n-butyrate, only a small percentage (approximately 4%) of the total beta A chromatin is in a soluble chromatin fraction following micrococcal nuclease digestion and centrifugation. This percentage increases to approximately 40-45% of the beta A chromatin if cells are incubated 1 hour in the presence of 10 mM sodium n-butyrate. The highest yield and enrichment of solubilized beta A chromatin is attained when 1-4% of the DNA is rendered acid soluble, and in buffers containing 1.5 - 5 mM MgCl2. The soluble beta A nucleohistone is nucleosome oligomer size (contains DNA 250-600 bases in length) and can be separated from soluble, transcriptionally inert mononucleosomes by agarose A-5m exclusion chromatography. The enhanced solubility appears to be specific for transcriptionally active chromatin. Whereas 40-45% of the beta A chromatin is recovered in the supernatant fraction from n-butyrate incubated immature erythrocytes, nucleohistone containing ovalbumin DNA sequences remains insoluble.
Acetylation↗
Clinical aspects of cutaneous leishmaniasis acquired in Texas.
Five patients with cutaneous leishmaniasis are described. Four of these patients acquired leishmaniasis in Texas. Four cases represent acute cutaneous leishmaniasis, and one case probably represents chronic cutaneous leishmaniasis. The classification and treatment of cutaneous leishmaniasis are reviewed. One patient in this report was successfully treated with topical antimony cream. Cutaneous leishmaniasis must be considered in the differential diagnosis of nonhealing ulcerated papules and nodules even in patients who do not have a foreign travel history.
Acute Disease↗