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Biomedical subjects

D A Nelson

Publications and source records attributed to D A Nelson.

At least 55 records · Page 3Linked to original sources

Whole body bone, fat and lean mass in children: comparison of three ethnic groups.

We measured whole body bone, fat and lean mass, by dual-energy x-ray absorptiometry, of third-grade children in a suburban public school district adjacent to Detroit. Of 1,340 eligible children, 773 participated. Using U.S. Census categories, parents identified their children as black/African-American (57%), white (38%), or one of several other categories (5%). Some of the participants also identified with a relatively large Middle Eastern subgroup (Chaldeans). Of the 773 participants, 734 are included in this report (71 Chaldeans, 226 whites, and 437 black/African-Americans; other categories are omitted). We describe body size, body composition, and physical activity levels in the three groups. The Chaldean and black children have significantly higher average whole body bone mineral content (BMC) than whites (P > 0.05), but are not different from each other. Lean mass and height are significantly greater for Chaldeans and blacks than for whites. The ratio of BMC to height was also significantly greater in Chaldeans and blacks compared with whites. Chaldeans have a significantly higher weight and fat mass than either the black or white children, and report significantly less physical activity than either the white or the black children. The higher bone mass among the Chaldean children may be partially explained by their greater body mass, but there is no readily apparent explanation for the observed ethnic differences in body size. We cannot exclude genetic or environmental factors not evaluated in this observational study. Our unexpected finding that Chaldean children, when analyzed as a separate group, are more similar in body composition to black/African-American than to white children contributes to a growing body of literature indicating that the uncritical use of "race" categories may obscure rather than facilitate the identification of population differences.

Adipose Tissue↗

Deficiency of neutrophilic granule membrane glycoproteins in the myelodysplastic syndromes: a common deficiency in 216 patients studied by the Cancer and Leukemia Group B.

Previous studies on neutrophils in patients with the myelodysplastic syndromes (MDS) have indicated deficiencies in the contents of primary and secondary granules. However, the granule membrane remains virtually unstudied despite its essential role in the dynamic function of the cytoplasmic granules. In this study, we examined the membrane glycoproteins of primary and secondary granules of peripheral blood and/or bone marrow neutrophils using the monoclonal antibody H36/71 to CD15 glycoproteins. In addition, myeloperoxidase activity and antigen, elastase and lactoferrin were also studied using cytochemical and immunocytochemical stains. A total of 216 patients were included. Deficiencies of granule membrane glycoproteins were the most common, detected in 49%, followed by myeloperoxidase activity (17%), elastase (16%), myeloperoxidase antigen (9%), and lactoferrin (8%). Multiple deficiencies always included granule membrane deficiency. We conclude that granule membrane defects are common in MDS, may provide a common mechanism for multiple granule deficiencies, and may prove to be an additional abnormality associated with granulocyte dysfunction.

Cytoplasmic Granules↗

Ethnic differences in the prevalence of asthma in middle class children.

BACKGROUND: Studies have shown a higher prevalence of asthma among boys compared with girls and in blacks compared with whites, but it has been difficult to separate socioeconomic from racial effects because the blacks in the studied populations were more likely to have low socioeconomic status. OBJECTIVE: To compare the prevalence of asthma in a socioeconomically homogeneous, middle class, multiethnic population of schoolchildren. METHODS: Based on a telephone survey of all families of third-graders in Southfield, Michigan, we ascertained the prevalence of physician-diagnosed asthma and probable undiagnosed asthma. One reason Southfield was chosen for study was because the city comprises an integrated middle class population with only 4% blacks and 7% whites having incomes below federal poverty limits. RESULTS: The lifetime prevalence of asthma was 9.5% (12% for blacks and 6% for whites) and higher in boys (14%) than girls (5%), a pattern that was reflected in period prevalence estimates. The lifetime prevalence of probable undiagnosed asthma was greater in blacks (16.6%) than whites (10.8%), with little sex difference. Adjusting for sex and maternal education, the prevalence of physician-diagnosed asthma and probable asthma were associated independently with black ethnicity. CONCLUSIONS: Our study is unique in the similarity of the black and white families' socioeconomic status and residence in the same middle class community. Since access to medical care and macro-environmental conditions were similar across this study population, our results are consistent with the hypothesis that differences in biologic factors between blacks and whites and boys and girls play a role in asthma risk.

Adolescent↗

The accumulation of whole body skeletal mass in third- and fourth-grade children: effects of age, gender, ethnicity, and body composition.

The purpose of this longitudinal study is to describe bone mass and body composition, and the annual changes in these measurements, among third grade students recruited from a suburban school district. Whole body bone mineral content (WBBMC), bone mineral density (WBBMD), fat, and lean mass were measured by dual-energy X-ray absorptiometry. Bone mass in the lumbar spine (LBMC) region of the whole body scan was also utilized. 773 students (38% white, 57% black, 5% other) had baseline visits; 561 had a second measurement a year later. At baseline, black children have significantly higher WBBMC, WBBMD, height, and lean mass than whites. Black males, but not black females, have a greater LBMC. There are no significant gender differences in body size, WBBMC, or WBBMD, although girls have a greater LBMC and fat mass, and boys have a higher lean mass. Most of these differences persist in visit 2. The annual change in bone and lean mass is greater in blacks. Stepwise linear regression analyses of bone mass on body size, gender, and ethnicity and their interactions indicate that log-transformed weight explains most of the variance in both WBBMC and WBBMD (multiple r2 = 0.90 and 0.64, respectively). There are significant black/white differences in intercepts and slopes. Other variables explain only another 1%-2% of the variance. The strongest Pearson correlations are between changes in bone mass and changes in lean mass and log-transformed weight (r ranging from 0.62 to 0.84, p = 0.0001). We conclude that there is a significant black/white, but not male/female difference in whole body bone mass and bone density before puberty. Ethnic and gender differences in bone and body composition suggest that the lean component may contribute to a greater peak bone mass in blacks vs. whites, and perhaps in males vs. females.

Absorptiometry, Photon↗

Linearized response growth inferred from growth-of-masking slopes in ears with cochlear hearing loss.

Growth of masking for OFF-frequency conditions (probe frequency above the masker spectrum) and ON-frequency conditions (probe within the masker spectrum) was investigated using simultaneous masking in three subjects with normal hearing and nine subjects with high-frequency sensorineural hearing loss. Growth-of-masking functions (probe thresholds as a function of masker intensity) for OFF-frequency conditions were obtained for probe tones placed at six frequencies above a 200-Hz-wide masker with an upper edge at 520 Hz. Growth-of-masking functions for ON-frequency conditions were obtained for probe tones placed within the 200-Hz-wide masker and for probe tones placed within 400-Hz-wide maskers with upper edges at 1040, 1300, 1627, and 2040 Hz (probe tones placed 20 Hz below the upper edge frequency). Growth-of-masking functions were fit with a power function of masker intensity added to an internal noise with intensity equal to the absolute threshold for the probe, and were well described by two free parameters and a threshold constant: the growth-of-masking slope (beta), a masking sensitivity constant (kappa) that indicated the minimum effective masker level at which masking began, and the intensity of the probe at absolute threshold (IT). For OFF-frequency masking conditions, growth-of-masking slopes (beta) decreased by a factor of 0.8 for every 10 dB of hearing loss. Comparisons with data from previous studies of upward spread of masking, and assumptions about underlying physiological mechanisms, led to the conclusion that more gradual than normal growth-of-masking slopes reflect larger (steeper) growth-of-response slopes at the probe frequency in regions of hearing loss. Derived response-growth exponents increased by a factor of 1.2 for every 10 dB of hearing loss (HL), from an exponent around 0.25 at 0 dB HL to an exponent around 1.0 at 75 dB HL (linear response growth). Masking sensitivity constants (kappa), the minimum effective masker levels, indicated that masking began at slightly higher masker levels in subjects with sensorineural hearing loss than in subjects with normal hearing. It was concluded that higher masked thresholds in regions of hearing loss were due primarily to a loss of active gain at the probe frequency and were not due to an excessive response at the probe frequency to the lower-frequency masker. For ON-frequency masking conditions, growth-of-masking slopes were not different from normal in hearing-impaired subjects. ON-frequency masking began when the effective power within an auditory filter at the probe frequency reached elevated absolute threshold at the probe frequency. Critical ratios were normal except for one subject with the most hearing loss.

Adult↗

Psychometric functions and temporal integration in electric hearing.

Temporal-integration functions and psychometric functions for detection were obtained in eight users of the Nucleus 22-electrode cochlear implant. Stimuli were 100-Hz, 200-microseconds/phase trains of biphasic pulses with durations ranging from 0.44 to 630.4 ms (1 to 64 pulses). Temporal-integration functions were measured for 21 electrodes. Slopes of these functions were considerably shallower than the 2.5 dB/doubling slopes typically observed in acoustic hearing. They varied widely across subjects and for different electrodes in a given subject, ranging from 0.06 to 1.94 dB/doubling of stimulus pulses, with a mean [standard deviation (s.d.)] value of 0.42 (0.38). Psychometric functions were measured for 11 of the same 21 electrodes. Slopes of psychometric functions also varied across subjects and electrodes, and were 2-20 times steeper than those reported by other investigators for normal-hearing and cochlear-impaired acoustic listeners. Slopes of individual psychometric functions for 1-, 2-, 4-, and 8-pulse stimuli ranged from 0.20 to 1.84 log d'/dB with a mean (s.d.) value of 0.77 (0.45). Psychometric-function slopes did not vary systematically with stimulus duration in most cases. A clear inverse relation between slopes of psychometric functions and slopes of temporal-integration functions was observed. This relation was reasonably well described by a hyperbolic function predicted by the multiple-looks model of temporal integration [Viemeister and Wakefield, J. Acoust. Soc. Am. 90, 858-865 (1991)]. Psychometric-function slopes tended to increase with absolute threshold and were inversely correlated with dynamic range, suggesting that observed differences in psychometric-function slopes across subjects and electrodes may reflect underlying differences in neural survival.

Adult↗

Whole body bone, fat, and lean mass in black and white men.

This research describes the effects of age, ethnicity, and body size and composition on whole body bone mass and bone density in healthy black and white men. We measured 79 male subjects, 42 white and 37 black, ranging in age from 33 to 64 years. Whole body bone mineral content (WBBMC) and bone mineral density (WBBMD), as well as fat and lean mass, were evaluated with a Hologic 1000W bone densitometer. We explore the utility of different methods of controlling for variations in body size in the two ethnic groups. There are statistically significant ethnic differences only in the bone mass variables. The black men had a 15% higher WBBMC (3111 vs. 2712 g, p < 0.0001) and a 8% higher WBBMD (1.25 vs. 1.16 g/cm2, p = 0.001) than the white men. Dividing WBBMD by height reduced the black/white difference to 6%. WBBMC, WBBMC/height, and WBBMD are strongly and significantly correlated with weight, body mass index (BMI), and body composition; correlations tended to be lower for WBBMD/height. Age is not significantly correlated with any of the variables in either ethnic group (p > or = 0.10). In multivariate linear regression models for predicting WBBMC or WBBMD, the two best models contained height, weight, and an interaction of ethnicity and weight (model r2 = 0.72 for WBBMC and r2 = 0.47 for WBBMD); and height, lean mass, and an ethnicity-fat interaction (model r2 = 0.69 for WBBMC and r2 = 0.46 for WBBMD). Using analysis of covariance, we found that controlling for lean mass and height reduced the black/white difference in bone mass from 14.7 to 9.8%.

Adipose Tissue↗

The high-affinity sulfonylurea receptor: distribution, glycosylation, purification, and immunoprecipitation of two forms from endocrine and neuroendocrine cell lines.

The high-affinity sulfonylurea receptor, a novel member of the ATP-binding cassette superfamily, is one component of the ATP-sensitive K+ channel. The protein is critical for regulation of insulin secretion from pancreatic beta-cells, and mutations in the receptor have been linked to familial hyperinsulinemia, a disorder characterized by unregulated insulin release despite severe hypoglycemia. The sulfonylurea receptor is present in membranes from a number of endocrine and neuroendocrine cell lines, including HIT-T15, RINm5f, alpha TC-6, AtT-20, and GH3 cells. Two forms of the receptor are present in RINm5f and alpha TC-6 cells, with apparent SDS gel molecular masses of 140 and 150 kDa. The two forms have equally high affinity, KD approximately 3 nM, for an iodinated derivative of glyburide, an anti-diabetic sulfonylurea. The receptor is a glycoprotein; treatment of RINm5f or alpha TC-6 cells with tunicamycin reduces the 140 and 150 kDa species to a single approximately 137 kDa protein. The 140 and 150 kDa receptors bind differentially to concanavalin A and wheat germ agglutinin, and lectin-affinity chromatography is ideal for the initial stages of receptor purification. After lectin-affinity chromatography, the same methods can be applied for purifying the 150 kDa form as for the 140 kDa receptor. A transiently expressed receptor with a histidine-tagged carboxy-terminus was purified by Ni-agarose chromatography, and this variant was used to demonstrate that the 140 kDa polypeptide is full length. Anti-peptide antibodies directed against the amino-terminus of the receptor and antibodies against the nucleotide binding folds immunoprecipitate both receptor forms. The results indicate the 140 and 150 kDa receptors are differentially glycosylated forms of the same polypeptide chain.

ATP-Binding Cassette Transporters↗

Clinical utility of bone mass measurements in adults: consensus of an international panel. The Society for Clinical Densitometry.

Low bone mass predicts future fracture risk as well as high cholesterol or high blood pressure can predict the risk of heart disease or stroke. Prevention of the first fracture should be a clinical goal. In patients without fractures, osteopenia and osteoporosis can be diagnosed based on the extent of reduction in bone mass below mean peak bone mass of young healthy individuals. As bone mass decreases, fracture risk increases exponentially. Clinical situations in which an assessment of bone mass and fracture risk affects therapeutic decisions include estrogen deficiency, vertebral abnormalities, radiographic osteopenia, asymptomatic primary hyperparathyroidism, and long-term corticosteroid therapy. Serial measurements can also be used to monitor the effects of osteoporosis treatments. The appropriate technique and skeletal site for bone mass measurements should be chosen based on the patient's circumstances and the precision of measurement. A clinical interpretation can enhance the value of computer-generated bone mass measurement reports and improve decision making.

Absorptiometry, Photon↗

Slopes of distortion-product otoacoustic emission growth curves corrected for noise-floor levels.

Distortion-product otoacoustic emission (DPE) input/output (I/O) curves were measured at 2f1-f2 frequencies with spectral-averaging and time-averaging procedures from ten normal-hearing ears. Stimuli were equal-level f1 and f2 primary tones with f2/f1 ratios of 1.2 and f2 frequencies at 1200, 2400, and 4800 Hz. Time-averaging procedures lowered noise-floor (NF) levels, compared to spectral averaging, so DPEs could be elicited by stimuli as low as 18 dB SPL in some ears. DPEs were corrected for power summation with NF levels and the resulting DPE I/O curves were fit with sixth-order polynomials. Slopes of fitted I/O curves were specified by the first derivative as a function of the level of the primary tones. Slopes of uncorrected spectrally averaged DPE I/O curves were strongly influenced by the NF level. Slopes of NF-corrected spectrally averaged DPE I/O curves were more representative of the true slope, specified as the slope of the corresponding time-averaged DPE I/O curve well above its NF. True DPE I/O slopes decreased with level from a mean slope near 1.0 dB/dB at 30 dB SPL and below for all three f2 frequencies. Nonmonotonicities in I/O curves were not seen at very low stimulus levels. At moderate stimulus levels and above, nonmonotonicities in individual DPE I/O curves reduced the slopes of individual I/O curves and reduced the average slopea cross ears.

Acoustic Stimulation↗

Release from upward spread of masking in regions of high-frequency hearing loss.

The upward spread of masking was compared for 500-Hz quasifrequency-modulated (QFM) and sinusoidally amplitude-modulated (SAM) maskers. The modulation rate was 20 Hz. These maskers had identical magnitude spectra but different envelopes, which were relatively flat for the QFM masker and strongly fluctuating for the SAM masker. At signal frequencies more than an octave above the masker, masked thresholds for the SAM masker were lower than for the QFM masker, revealing "masking release" (QFM-SAM masked threshold differences) exceeding 30 dB in normal-hearing ears. In ears with high-frequency sensorineural hearing loss, but normal hearing in the region of the masker, masking release was markedly reduced or completely absent in regions of hearing loss. The data were evaluated with a model of masking based on the linearized response growth (LRG) of basilar membrane transfer functions associated with cochlear damage in animals. The LRG model predicted more gradual slopes of the growth of masking and reduced amount of masking in regions of hearing loss. The reduced masking release seen in regions of hearing loss could be largely accounted for by a more rapid growth of response to the probe tone in regions of hearing loss.

Auditory Perception↗

Intensity discrimination as a function of stimulus level with electric stimulation.

Difference limens (DLs) for changes in electric current were measured from multiple electrodes in each of eight cochlear-implanted subjects. Stimuli were 200-microseconds/phase biphasic pulse trains delivered at 125 Hz in 300-ms bursts. DLs were measured with an adaptive three-alternative forced-choice procedure. Fixed-level psychometric functions were also obtained in four subjects to validate the adaptive DLs. Relative intensity DLs, specified as Weber fractions in decibels [10 log (delta I/I)] for standards above absolute threshold, decreased as a power function of stimulus intensity relative to absolute threshold [delta I/I = beta (I/I0) alpha] in the same manner as Weber fractions for normal acoustic stimulation reported in previous studies. Exponents (alpha) of the power function for electric stimulation ranged from -0.4 to -3.2, on average, an order of magnitude larger than exponents for acoustic stimulation, which range from -0.07 to -0.11. Normalization of stimulus intensity to the dynamic range of hearing resulted in Weber functions with similar negative slopes for electric and acoustic stimulation, corresponding to an 8-dB average improvement in Weber fractions across the dynamic range. Sensitivity to intensity change ¿10 log beta¿ varied from -0.42 to -13.5 dB compared to +0.60 to -3.34 dB for acoustic stimulation, but on average was better with electric stimulation than with acoustic stimulation. Psychometric functions for intensity discrimination yielded Weber fractions consistent with adaptive procedures and d' was a linear function of delta I. Variability among repeated Weber-fraction estimates was constant across dynamic range. Relatively constant Weber fractions across all or part of the dynamic range, observed in some subjects, were traced to the intensity resolution limits of individual implanted receiver/stimulators. DLs could not be accurately described by constant amplitude changes, expressed as a percentage of dynamic range ¿delta A(% DR)¿. Weber fractions from prelingually deafened subjects were no better or worse than those from postlingually deafened subjects. The cumulative number of discriminable intensity steps across the dynamic range of electric hearing ranged from as few as 6.6 to as many as 45.2. Physiologic factors that may determine important features of electric intensity discrimination are discussed in the context of a simple, qualitative, rate-based model. These factors include the lack of compressive cochlear preprocessing, the relative steepness of neural rate-intensity functions, and individual differences in patterns of neural survival.

Auditory Threshold↗

Cloning of the beta cell high-affinity sulfonylurea receptor: a regulator of insulin secretion.

Sulfonylureas are a class of drugs widely used to promote insulin secretion in the treatment of non-insulin-dependent diabetes mellitus. These drugs interact with the sulfonylurea receptor of pancreatic beta cells and inhibit the conductance of adenosine triphosphate (ATP)-dependent potassium (KATP) channels. Cloning of complementary DNAs for the high-affinity sulfonylurea receptor indicates that it is a member of the ATP-binding cassette or traffic ATPase superfamily with multiple membrane-spanning domains and two nucleotide binding folds. The results suggest that the sulfonylurea receptor may sense changes in ATP and ADP concentration, affect KATP channel activity, and thereby modulate insulin release.

ATP-Binding Cassette Transporters↗