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Biomedical subjects

D W Chandler

Publications and source records attributed to D W Chandler.

At least 19 recordsLinked to original sources

Differential cross sections for collisions of hexapole state-selected NO with He.

The first measurements of differential inelastic collision cross sections of fully state-selected NO (j=12, Omega=12, epsilon= -1) with He are presented. Full state selection is achieved by a 2 m long hexapole, which allows for a systematic study of the effect of parity conservation and breaking on the differential cross section. The collisionally excited NO molecules are detected using a resonant (1+1') REMPI ionization scheme in combination with the velocity-mapped, ion-imaging technique. The current experimental configuration minimizes the contribution of noncolliding NO molecules in other rotational states j, Omega, epsilon--that contaminates images--and allows for study of the collision process at an unprecedented level of detail. A simple method to correct ion images for collision-induced alignment is presented as well and its performance is demonstrated. The present results show a significant difference between differential cross sections for scattering into the upper and lower component of the Lambda-doublet of NO. This result cannot be due to the energy splitting between these components.

Journal Article↗

Direct measurement of the preferred sense of NO rotation after collision with argon.

The preferred sense of product molecule rotation (clockwise or counterclockwise) in a bimolecular collision system has been measured. Rotationally inelastic collisions of nitric oxide (NO) molecules with Ar atoms were studied by combining crossed molecular beams, circularly polarized resonant multiphoton ionization probing, and velocity-mapped ion imaging detection. The observed sense of NO product rotation varies with deflection angle and is a strong function of the NO final rotational state. The largest preferences for sense of rotation are observed at the highest kinematically allowed product rotational states; for lower rotational states, the variation with deflection angle becomes oscillatory. Quantum calculations on the most recently reported NO-Ar potential give good agreement with the observed oscillation patterns in the sense of rotation.

Journal Article↗

Serum hormones and the alcohol-breast cancer association in postmenopausal women.

BACKGROUND: Alcohol ingestion is associated with an increased risk of breast cancer in most epidemiologic studies. Results, however, are heterogeneous at lower levels of alcohol intake, and a biologic mechanism for the association has not been clearly identified. To determine whether alcohol consumption by postmenopausal women elevates serum levels of hormones associated with an increased risk of breast cancer, we performed a controlled feeding study. METHODS: Participants were 51 healthy postmenopausal women not using hormone replacement therapy. Each participant rotated through three 8-week dietary periods in which she consumed 15 or 30 g of alcohol per day or an alcohol-free placebo beverage. The order of assignment to the three alcohol levels was random. During the dietary periods, all food and beverages were supplied by the study, and energy intake was adjusted to keep body weight constant. Levels of estradiol, estrone, estrone sulfate, testosterone, androstenedione, progesterone, dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), and androstenediol were measured by radioimmunoassays in serum collected at the end of each dietary period. All statistical tests are two-sided. RESULTS: When women consumed 15 or 30 g of alcohol per day, respectively, estrone sulfate concentrations increased by 7.5% (95% confidence interval [CI] = -0.3% to 15.9%; P =.06) and 10.7% (95% CI = 2.7% to 19.3%; P =.009) and DHEAS concentrations increased by 5.1% (95% CI = 1.4% to 9.0%; P =.008) and 7.5% (95% CI = 3.7% to 11.5%; P<.001) relative to levels when women consumed placebo. None of the other hormones measured changed statistically significantly when women consumed alcohol. CONCLUSIONS: Results suggest a possible mechanism by which consumption of one or two alcoholic drinks per day by postmenopausal women could increase their risk of breast cancer.

Aged↗

The longitudinal study of adrenal maturation during gonadal suppression: evidence that adrenarche is a gradual process.

The physical changes that herald the onset of puberty result from the combination of adrenarche and gonadarche. To examine adrenal maturation and associated changes in growth without the confounding effects of changes in the gonadal steroid milieu, we performed a longitudinal study in 14 young girls with idiopathic central precocious puberty during long-term pituitary-gonadal suppression. Beginning at the mean age of 2.9 yr, dehydroepiandrosterone sulfate levels, linear growth, skeletal maturation, body mass index, and secondary sexual development were evaluated at 3- to 6-month intervals for up to 12.3 yr. In 12 of the girls, levels of dehydroepiandrosterone, androstenedione, 17-hydroxypregnenolone, and 17alpha-hydroxyprogesterone were determined before and after acute ACTH stimulation every 6 months to investigate the maturation of adrenal steroidogenic enzyme activity. Serum dehydroepiandrosterone sulfate levels rose progressively throughout the study. An exponential model fit the longitudinal datasets well and indicated that dehydroepiandrosterone sulfate levels increased approximately 22%/yr from the youngest age onward. Increasing activity of 17-20 lyase (CYP17) and decreasing activity of 3beta-hydroxysteroid dehydrogenase were also evident in preadrenarchal subjects. When controlled for chronological age, no significant associations were noted between weight, body mass index, or body surface area and dehydroepiandrosterone sulfate levels. However, similar analyses revealed modest correlations of both height and growth velocity with dehydroepiandrosterone sulfate levels. Our results suggest that adrenarche is not the result of sudden rapid changes in adrenal enzyme activities or adrenal androgen concentrations; rather, adrenarche may be a gradual maturational process that begins in early childhood.

17-Hydroxysteroid Dehydrogenases↗

Femtosecond time-resolved photoelectron angular distributions probed during photodissociation of NO2.

Femtosecond time-resolved photoelectron angular distributions (PADs) are measured for the first time in the molecular frame of a dissociating molecule. Various stages of the dissociation process, NO2-->NO(C Pi)+O(P), are probed using ionization of the NO(C Pi) fragment to NO+(X Sigma(+)). The PADs evolve from forward-backward asymmetric with respect to the dissociation axis at short time delays ( < or =500 fs) to symmetric at long time delays (> or = 1 ps). Changes in the PADs directly reflect the time-dependent separation and reorientation of the dissociating photofragments.

Journal Article↗

Paper chromatography prior to cortisol RIA allows for accurate use of the dexamethasone suppression test in chronic renal failure.

The assessment of the hypothalamic-pituitary-adrenal axis in patients with chronic renal failure (CRF) on hemodialysis is often hampered by abnormal responses to the standard 1-mg dexamethasone suppression test. Various mechanisms have been proposed to explain this lack of suppressibility. The present study was designed to look into the mechanisms possible for these findings in patients with CRF. We studied 6 patients with CRF on hemodialysis and 5 healthy subjects utilizing the 1-mg dexamethasone suppression test as well as the 50-mg hydrocortisone suppression test. Samples were assayed for dexamethasone, adrenocorticotropic hormone, corticosterone, and cortisol by both direct radioimmunoassay (RIA) and RIA after paper chromatography. Utilizing the direct cortisol RIA, 4 of 6 patients with CRF exhibited blunted dexamethasone suppression, while all 6 patients showed normal suppressibility after dexamethasone when cortisol was measured after paper chromatography. In contrast, all controls showed normal suppressibility regardless of the cortisol assay procedure used. The hydrocortisone suppression test was unreliable in the setting of CRF. Mean dexamethasone levels were similar in both groups. Plasma adrenocorticotropic hormone levels were significantly higher in the CRF patients, possibly indicative of an underlying hypothalamic-pituitary-adrenal axis abnormality. Abnormalities in dexamethasone suppression testing in patients with CRF may be explained by the overestimation of cortisol levels by direct RIA rather than by alteration of dexamethasone absorption or metabolism. Measurement of cortisol after paper chromatography is superior to direct RIA of cortisol in patients with CRF.

Adrenocorticotropic Hormone↗

Relationships of serum androgens and estrogens to prostate cancer risk: results from a prospective study in Finland.

Several lines of evidence suggest that sex hormones may be involved in the etiology of prostate cancer. We conducted a prospective nested case-control study to evaluate the relationships of serum androgens and estrogens to prostate cancer using serum collected at baseline for the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. The 29,133 male smokers who participated in the trial were 50-69 years old at baseline. During 5-8 years of follow-up, 246 men were diagnosed with prostate cancer, and 116 of these were randomly selected for inclusion in the current study. For each case, two controls matched on age, date of blood collection, intervention group, and study center were selected. Hormones were measured in serum by RIA using standard procedures. None of the individual androgens or estrogens was significantly related to prostate cancer. These findings were unaltered by simultaneous evaluation of serum androgen and estrogen concentrations in multivariate models. These results do not support a strong relationship of serum androgens and estrogens with prostate cancer in smokers. Within-person variation in concentrations of some hormones may have contributed to the lack of significant associations.

Aged↗

Effects of blast overpressure on the ear: case reports.

The case histories of five patients who experienced blast overpressure in excess of 200-dB peak pressure level are presented. Despite the significance of the sound pressure levels received in a military training accident and the severe injuries that resulted from the blast, these individuals experienced substantial improvement of hearing 1 year later. Undoubtedly, successful surgical intervention and medical management were the primary contributors to the restoration of hearing. Audiometric data are presented documenting hearing status within 2 to 3 weeks postinjury and following final surgical remediation of the resulting middle ear damage. A review of these cases offers insight into the possible prognosis of patients with similar injuries.

Adult↗

Reproducibility studies and interlaboratory concordance for assays of serum hormone levels: estrone, estradiol, estrone sulfate, and progesterone.

We conducted studies to measure sources of assay variability for estrone, estradiol, estrone sulfate, and progesterone for postmenopausal women (n = 5) and for women in the mid-follicular (n = 5) and mid-luteal (n = 5) phases of the menstrual cycle. A single blood sample from each woman was divided into 2.5-ml aliquots and stored at -70 degrees C, and sets of two aliquots were sent at monthly intervals to each of three laboratories (four for progesterone). Each aliquot was analyzed in duplicate. Thus, within each menstrual category, we were able to estimate the components of variance due to variation among women, variation among aliquots, variation among duplicate measurements, and variation among the 4 analysis days. Using the logarithm of assay measurements, we estimated the percentage of variance attributable to variation among women in each menstrual category, 100 rho, is the estimated intraclass correlation. For each assay, 100 rho exceeded 90% for mid-follicular and mid-luteal women. For postmenopausal women, values of 100 rho exceed 84% for estrone in two laboratories. Values of 100 rho were lower for progesterone in postmenopausal women, although a value of 84% was estimated from one laboratory. These studies indicate that estrogen assays over a period of 3 months permit reliable comparisons among women in a given menstrual category. Progesterone measurements are likewise reliable for women in the mid-follicular and mid-luteal phases but somewhat less satisfactory for postmenopausal women. These assessments of variability pertain only to laboratory techniques and do not allow for secular variation in intra-woman hormone levels. Moreover, although these measurements tend to be reliable enough for making comparisons among women, estimates of coefficients of variation for estrogens are about 10% for mid-follicular and mid-luteal phase women and about 11-20% for postmenopausal women. Coefficients of variation for progesterone are about 10% for mid-luteal, 20% for mid-follicular, and 30% for postmenopausal women.

Analysis of Variance↗

Testosterone and aggression in children.

OBJECTIVE: A link between serum testosterone and aggressive behavior, which has been demonstrated in numerous animal studies and suggested in several studies of adult men, has never been investigated in children before the time of puberty. METHOD: We measured serum testosterone, sex hormone binding globulin (SHBG), dehydroepiandrosterone (DHEA), and dehydroepiandrosterone sulfate (DHEAS) in 18 highly aggressive prepubertal boys, ages 4 to 10, hospitalized for violent or unmanageable behavior at a state children's psychiatric facility in New York City (the Bronx). We compared them with a group of age and race matched controls from the same demographic area, screened negative for aggressive behavior problems. All the aggressive subjects met DSM-III-R criteria for conduct disorder and scored higher than the 98th percentile on the aggression subscale of the Child Behavior Checklist (mean T = 80 for the group). RESULTS: There were no significant differences between aggressive and nonaggressive children for T, SHBG, DHEA, DHEAS, or ratios of combinations of these variables. CONCLUSIONS: These findings raise questions about inferences from adult studies that testosterone may play a causal role in the development of human aggression. Testosterone does not appear to be a useful biological marker for aggressivity in early childhood.

Aggression↗

Minimum audible movement angle in the horizontal plane as a function of stimulus frequency and bandwidth, source azimuth, and velocity.

Minimum audible movement angles (MAMAs) were measured in the horizontal plane for four normal-hearing adult subjects in a darkened anechoic chamber. On each trial, a single stimulus was presented, and the subject had to say whether it came from a stationary loudspeaker or from a loudspeaker that was moving at a constant angular velocity around him. Thresholds were established by adaptively varying stimulus duration. In experiment 1, MAMAs were measured as a function of center frequency (500-5000 Hz), velocity (10 degrees-180 degrees/s), and direction of motion (left versus right). There was no effect of direction of motion. MAMAs increased with velocity, from an average of 8.8 degrees of arc for a target moving at 10 degrees/s to an average of 20.2 degrees of arc for a target moving at 180 degrees/s. MAMAs were higher for a 3000-Hz tone than for tones of lower or higher frequencies, as has been previously reported [D. R. Perrott and J. Tucker, J. Acoust. Soc. Am. 83, 1522-1527 (1988)]. In experiment 2, minimum audible angles (MAAs) were measured with sequentially presented stationary tone pulses (500-5000 Hz), and were shown to exhibit the same dependence on signal frequency that the MAMAs showed (average MAA at 3000 Hz: 8.4 degrees; average MAA at the other frequencies: 3.4 degrees). In experiment 3, MAMAs and MAAs were measured as a function of stimulus bandwidth (centered at 3000 Hz) and listening azimuth (0 degrees vs 60 degrees). Average MAAs decreased monotonically as stimulus bandwidth increased from 0 Hz to wideband (from 8.4 degrees to 1.2 degrees at 0 degrees azimuth; from 11.3 degrees to 1.5 degrees at 60 degrees azimuth). As in experiment 1, MAMAs increased with stimulus velocity, from values comparable to the MAAs for the slowest-velocity (10 degrees/s) targets to 70 degrees of arc or more in the poorest condition (third-octave band of noise presented at a velocity of 180 degrees/s and an azimuth of 60 degrees). MAMAs obtained in the slower-velocity conditions depended in the same way on stimulus bandwidth and listening azimuth that MAAs depended on these variables. In no case was the MAMA ever smaller than the MAA. It is hypothesized that a minimum integration time is required to achieve optimal performance in a dynamic spatial resolution task. Average estimates of this minimum time based on the current data vary from 336 ms (for targets presented at midline) to 1116 ms (for narrow-band targets presented at 60 degrees azimuth).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Specific termination of in vitro transcription by calf thymus RNA polymerase III.

In vitro transcription of cleaved SV40 DNA with calf thymus RNA polymerase reveals a discrete transcript. The pattern of resistance to the inhibitor alpha-amanitin identifies the RNA as a product of RNA polymerase III transcription. The RNA is shown to initiate artificially near a DNA terminus created by cleavage and to terminate specifically near a cluster of 8 thymidine residues within the SV40 control region. Faithfully initiated transcripts cannot be detected using the calf thymus enzyme, supporting the idea that polymerase III termination can be accomplished by an initiation-deficient enzyme. Transcription of SV40 DNA in a HeLa cell lysate also leads to specific polymerase III transcription. When PvuII-cleaved DNA is the template, the same RNA is produced as with the calf thymus enzyme. At the lowered lysate concentration known to activate certain AluI-family transcripts, a collection of SV40 polymerase III transcripts is also produced. These do not depend on restriction cleavage of the DNA and thus arise from transcription of intact DNA.

Amanitins↗

The role of corticosteroids in the regulation of myocardial Na, K-ATPase in normotensive and spontaneously hypertensive rats.

Sodium, potassium-dependent adenosine triphosphatase (ATPase) of the renal tubule is known to be dependent on both gluco- and mineralocorticoids. Recent evidence suggests that corticosteroids may modulate ATPase activity at extrarenal sites. The myocardium contains glucocorticoid receptors to which mineralocorticoids can also bind. Thus, the possibility that myocardial ATPase is corticosteroid dependent was examined in the Wistar-Kyoto (WKY) normotensive rat and also in the spontaneously hypertensive (SH) rat, a strain previously shown to exhibit reduced myocardial ATPase activity. WKY and SH rats (in groups of 10) were either sham operated or adrenalectomized and placed on 1% NaCl solution as drinking water. Adrenalectomized rats subsequently received daily intraperitoneal injections of either vehicle (1% NaCl, 0.5 ml), aldosterone (30 micrograms/kg) or dexamethasone (60 micrograms/kg). Renal cortical and myocardial ATPase activities were determined 21 days later in all groups. Adrenalectomized WKY rats had reduced myocardial ATPase activity (5.15 +/- 0.88 vs 8.18 +/- 0.93 mumol of phosphate h-1 mg-1 of protein in controls; P less than 0.01). This observed decrease in ATPase in adrenalectomized rats could be at least partly prevented by selective aldosterone or dexamethasone replacement. Parallel changes were observed with renal cortical ATPase. SH rat myocardial ATPase was lower than in WKY rats (P less than 0.05, 5.88 +/- 0.99 mumol of phosphate h-1 mg-1 of protein) and was unaffected by adrenalectomy (5.47 +/- 0.68 mumol of phosphate h-1 mg-1 of protein) whether accompanied by aldosterone (6.08 +/- 0.68 mumol of phosphate h-1 mg-1 of protein) or dexamethasone (6.47 +/- 0.84 mumol of phosphate h-1 mg-1 of protein) therapy or not.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Hormones↗

Hearing levels in U.S. Army engineers.

An 18-item questionnaire on otoaudiological and noise-exposure history was completed by over 900 U.S. Army engineers, of whom reference and current audiograms were collected on 209 Ss who reported no obvious ear or hearing problems and did not participate in non-military noise-hazardous hobbies or activities. Subgroups of 6 military occupation specialties were studied separately; differences among these were unremarkable in age, length of military service, and job-related noise exposure, in current HTLs and in hearing losses re reference audiogram prior to appreciable military noise exposure. Mean current HTLs were better 3, 4 and 6 kc/s by about 23, 34, and 24 db (L + L ears) than a comparably-aged group of 450 men working in industry (Glorig et al, 1957). These results augur well for the current Army hearing conservation program.

Adult↗

Comparison of occupational hearing losses among military engineers and their civilian counterparts.

A previous study (Chandler and Fletcher, J. Aud. Res., 1983, 23, 23-32) examined group hearing loss of 209 U.S. Army engineers by comparing current with reference audiograms. The sample was categorized by military occupation specialty, age, and time on job. The present study reports comparable data for 187 civilian engineers on the same Army post exposed to essentially the same noise. These had less hearing loss than their military counterparts. Some reasons are suggested, such as attrition of the civilian workforce because of hearing problems, and a likely greater exposure of the military engineers to noises not job-related. Age was less important than time on the job. Both groups, however, exhibited significantly lower hearing levels than the industrial population of Glorig et al (Am. Acad. Ophthalmol. Otolaryngol., 1957) at the 1954 Wisconsin State Fair, possibly because both military and civilian personnel at this Army post had been for some years in an aggressive hearing conservation program.

Adolescent↗

Dopaminergic modulation of 18-hydroxycorticosterone secretion in man.

This study was designed to investigate mechanisms of dopaminergic control of corticosteroid secretion and to determine on which step in the aldosterone biosynthetic pathway dopamine exerts its effects. Plasma concentrations of electrolytes, PRA, plasma cortisol, 11-deoxycorticosterone, corticosterone (18-OHB), and 18-hydroxy-11-deoxycorticosterone were not altered by the iv administration of 10 mg metoclopramide in six healthy male volunteers. Metoclopramide increased plasma aldosterone from 6.3 +/- 0.9 ng/dl to a maximum of 23.0 +/- 3.4 ng/dl, plasma 18-OHB from 11.4 +/- 1.1 ng/dl to a maximum level of 42.8 +/- 4.4 ng/dl, and PRL from 9.9 +/- 1.4 ng/ml to a maximum of 71.0 +/- 5.5 ng/ml. The aldosterone and 18-OHB responses displayed a parallel time course, with significant responses of both occurring with 5 min after metoclopramide administration. Dopamine infusions (3 micrograms/kg . min) begun 60 min before the administration of metoclopramide markedly decreased the 18-OHB as well as the aldosterone and PRL responses to the dopamine antagonist. A parallel time course of stimulation of 18-OHB and aldosterone secretion with no change in other aldosterone precursors suggests that dopamine may modulate the activity of the glomerulosa 18-hydroxylase enzyme. Thus, rather than simply affecting aldosterone secretion, dopaminergic mechanisms appear to modulate the biosynthesis of aldosterone.

18-Hydroxycorticosterone↗