Biomedical subjects

J E Olson

Publications and source records attributed to J E Olson.

At least 19 recordsLinked to original sources

PubMed2006

Pilot study of the impact of letrozole vs. placebo on breast density in women completing 5 years of tamoxifen.

Breast density, a strong risk factor for breast cancer, is reduced by the anti-estrogen, tamoxifen (TAM). We examined whether aromatase inhibitor (AI) therapy results in further reductions in breast density among women completing 5 years of TAM. Among a sample of women with early-onset breast cancer who were randomized to letrozole (LET)(n=56) or placebo (PLAC)(n=48) after 5 years of TAM, we examine the change in percent density at 9-15 months as well as a per-year change in PD by treatment group. There was no difference in the adjusted mean change (-1.0%, LET; -0.3%, PLAC (P=0.58)) or the percentage change (-2.7%, LET; -3.0%, PLAC (P=0.96)) in PD between treatment groups at 9-15 months. Results were similar for longitudinal change (-0.68% per year, LET; -0.12% per year, PLAC (P=0.23)). Breast density does not appear to be a clinically relevant biomarker in women who already have low PD following 5 years of TAM.

Adult↗

PubMed2006

Regression analysis for comparing protein samples with 16O/18O stable-isotope labeled mass spectrometry.

MOTIVATION: Using stable isotopes in global proteome scans, labeled molecules from one sample are pooled with unlabeled molecules from another sample and subsequently subjected to mass-spectral analysis. Stable-isotope methodologies make use of the fact that identical molecules of different stable-isotope compositions are differentiated in a mass spectrometer and are represented in a mass spectrum as distinct isotopic clusters with a known mass shift. We describe two multivariable linear regression models for (16)O/(18)O stable-isotope labeled data that jointly model pairs of resolved isotopic clusters from the same peptide and quantify the abundance present in each of the two biological samples while concurrently accounting for peptide-specific incorporation rates of the heavy isotope. The abundance measure for each peptide from the two biological samples is then used in down-stream statistical analyses, e.g. differential expression analysis. Because the multivariable regression models are able to correct for the abundance of the labeled peptide that appear as an unlabeled peptide due to the inability to exchange the natural C-terminal oxygen for the heavy isotope, they are particularly advantageous for a two-step digestion/labeling procedure. We discuss how estimates from the regression model are used to quantify the variability of the estimated abundance measures for the paired samples. Although discussed in the context of (16)O/(18)O stable-isotope labeled data, the multivariable regression models are generalizable to other stable-isotope labeled technologies.

Algorithms↗

PubMed2003

Taurine enhances volume regulation in hippocampal slices swollen osmotically.

Cell volume regulation has been studied in neuronal and glial cultures but little is known about volume regulation in brain tissue with an intact extracellular space. We investigated volume regulation in hippocampal slices maintained in an interface chamber and exposed to hypo-osmotic medium. Relative changes in intracellular and extracellular volume were measured respectively as changes in light transmittance and extracellular resistance. Slices exposed to hypo-osmotic medium (200-240 mOsm/L) showed a decrease in light transmittance, which occasionally was preceded by a brief transient increase. However, hypo-osmotic exposure was always accompanied by a monotonic increase in extracellular resistance. Peak changes in light transmittance and extracellular resistance occurred at 15-20 min following exposure to hypo-osmotic medium. Optical evidence of volume regulation (RVD) was observed in six of 12 slices and occurred over the next 60-90 min. We hypothesized that the relatively low incidence of RVD was related to depletion of taurine, an osmolyte known to play an important role in volume regulation, during preparation of the slices. Indeed, taurine levels in freshly prepared slices were <50% of those reported in intact hippocampus. Incubation of slices in 1 mM taurine restored taurine to levels observed in situ and increased both the likelihood and magnitude of RVD in hypo-osmotic medium. Inhibition of taurine flux with 100 microM 5-nitro-2-(3 phenylpropylamino) benzoic acid blocked both RVD and the transient undershoot of volume commonly associated with return of swollen slices to iso-osmotic medium. Taurine treatment had no effect on levels of several other amino acids but preserved slice potassium content. The results indicate a critical role for cellular taurine during hypo-osmotic volume regulation in hippocampal slices. Inconsistencies between optical measurements of cellular volume changes and electrical measurements of extracellular space are likely to result from the complex nature of light transmittance in the interface slice preparation.

Adenosine Triphosphate↗

PubMed2003

Ion-molecule reactions of gas-phase chromium oxyanions. CrxOyHz-+ O2.

Chromium oxyanions, Cr(x)O(y)H(z)(-), were generated in the gas-phase using a quadrupole ion trap secondary ion mass spectrometer (IT-SIMS), where they were reacted with O(2). Only CrO(2)(-) of the Cr(1)O(y)H(z)(-) envelope was observed to react with oxygen, producing primarily CrO(3)(-). The rate constant for the reaction of CrO(2)(-) with O(2) was approximately 38% of the Langevin collision constant at 310 K. CrO(3)(-), CrO(4)(-), and CrO(4)H(-) were unreactive with O(2) in the ion trap. In contrast, Cr(2)O(4)(-) was observed to react with O(2) producing CrO(3)(-) + CrO(3) via oxidative degradation at a rate that was approximately 15% efficient. The presence of background water facilitated the reaction of Cr(2)O(4)(-) + H(2)O to form Cr(2)O(5)H(2)(-); the hydrated product ion Cr(2)O(5)H(2)(-) reacted with O(2) to form Cr(2)O(6)(-) (with concurrent elimination of H(2)O) at a rate that was 6% efficient. Cr(2)O(5)(-) also reacted with O(2) to form Cr(2)O(7)(-) (4% efficient) and Cr(2)O(6)(-) + O (2% efficient); these reactions proceeded in parallel. By comparison, Cr(2)O(6)(-) was unreactive with O(2), and in fact, no further O(2) addition could be observed for any of the Cr(2)O(6)H(z)(-) anions. Generalizing, Cr(x)O(y)H(z)(-) species that have low coordinate, low oxidation state metal centers are susceptible to O(2) oxidation. However, when the metal coordination is >3, or when the formal oxidation state is > or =5, reactivity stops.

Journal Article↗

PubMed2002

Adenocarcinoma of the lung is strongly associated with cigarette smoking: further evidence from a prospective study of women.

In a prospective cohort of 41,836 Iowa women aged 55-69 years with 13 years of follow-up from 1986 through 1998, the authors examined the association between cigarette smoking history and three common histologic subtypes of lung cancer (123 small cell, 115 squamous cell, and 234 adenocarcinoma). Using Cox proportional hazards and additive Poisson regression analysis, they estimated four epidemiologic measures of effect: age-adjusted incidence rate, relative risk, excess risk (or risk difference), and population attributable risk. Of the three major lung cancer subtypes, the excess risk for heavy smokers compared with never smokers was higher for adenocarcinoma (excess risk = 206) than for squamous cell (excess risk = 122) and small cell (excess risk = 104) carcinomas. Adenocarcinoma of the lung is more strongly associated with tobacco smoke exposure than previously recognized.

Adenocarcinoma↗

PubMed2002

Differential association of body mass index and fat distribution with three major histologic types of lung cancer: evidence from a cohort of older women.

The Iowa Women's Health Study, a prospective cohort study of 41,836 Iowa women aged 55-69 years at baseline in 1986, reported that lung cancer was inversely associated with body mass index (BMI) and waist/hip ratio. Risk by histologic subtype was not examined. Through 1998, 596 cases of lung cancer were identified. After adjustment for established risk factors, women in the upper BMI quintile were at decreased risk of all lung cancer subtypes, especially squamous cell carcinoma; the highest versus the lowest quintile of BMI was associated with a relative risk of 0.22 (p-trend = 0.005). Conversely, the highest quintile of waist circumference was positively associated with small cell and squamous cell lung cancer (relative risks = 3.31 and 3.05, respectively). No association of waist circumference with risk of adenocarcinoma of the lung was found. There were too few cases of squamous cell and small cell carcinoma in never smokers to eliminate the possibility that these results are due to the residual effects of smoking. Alternatively, these results may reflect increased activation of chemicals from cigarette smoke among women with an increased waist circumference. Results suggest that waist circumference may be differentially associated with histologic subtypes of lung cancer.

Aged↗

PubMed2001

Evidence for a major gene influence on abdominal fat distribution: the Minnesota Breast Cancer Family Study.

Abdominal fat has been shown to be an important risk factor for many chronic conditions, including diabetes, heart disease, and breast cancer. The objective of this study was to provide evidence for a major gene influence on the ratio of waist to hip circumference (WHR), a measurement commonly used in large scale studies to indicate the presence of abdominal fat. Segregation analysis was conducted on three subsets of families from the Minnesota Breast Cancer Family Study. One analysis was conducted among families with WHR measurements on all women. Two additional analyses were conducted on subsets of women stratified on menopausal status. Multiple regression analysis was used to identify factors associated with WHR expressed as a continuous trait. Complex segregation analyses were performed on the continuous trait of WHR and the covariates identified in the regression analysis. In the analysis of all women, all hypotheses were rejected. Among premenopausal women, the environmental hypothesis with no heterogeneity between generations fit the data best (P = 0.85). However, among postmenopausal women, the requirements for conclusion of the presence of a major gene were met. All non-Mendelian hypotheses were rejected (P < 0.0001), but the additive hypothesis was not rejected (P = 0.19) and provided the best fit to the data. The putative major gene identified by this model accounted for 42% of total phenotypic variance in WHR among these postmenopausal women. The allele for high WHR had a frequency of 27%. These findings support the hypothesis that the distribution of abdominal fat in postmenopausal women is under genetic control.

Abdomen↗

PubMed2001

Dietary folate intake, alcohol, and risk of breast cancer in a prospective study of postmenopausal women.

Low B-vitamin intake may increase risk of breast cancer through decreased DNA repair capacity. Alcohol intake increases risk for breast cancer, with evidence from prospective studies of an interaction between alcohol and folate. We explored dietary intake of folate and other B vitamins with risk of breast cancer in a cohort study of 34,387 postmenopausal women. To measure diet, we mailed a food frequency questionnaire; we estimated nutrient intakes and categorized them into four levels: <10th, 11th-30th, 31st-50th, and >50th percentiles. Through 12 years of follow-up, we identified 1,586 cases of breast cancer in the cohort at risk. We estimated relative risks (RRs) and 95% confidence intervals (CIs) through Cox regression models adjusted for age, energy, and other risk factors. Women in the lowest 10th percentile of folate intake from diet alone were at modestly increased risk of breast cancer relative to those above the 50th percentile: RR = 1.21 (95% CI = 0.91--1.61). We examined the joint association of folate intake and alcohol use on risk of breast cancer, with the reference group defined as women with high folate (>50th percentile) and no alcohol use. The RRs of breast cancer associated with low dietary folate intake were 1.08 (95% CI = 0.78--1.49) among nondrinkers, 1.33 (95% CI = 0.86--2.05) among drinkers of < or = 4 gm per day, and 1.59 (95% CI = 1.05--2.41) among drinkers of > 4 gm per day. These results suggest that the risks of postmenopausal breast cancer may be increased among women with low intakes of folate if they consume alcohol-containing beverages.

Aged↗

PubMed2001

Oxygen measurements in brain stem slices exposed to normobaric hyperoxia and hyperbaric oxygen.

We previously reported (J Appl Physiol 89: 807-822, 2000) that < or =10 min of hyperbaric oxygen (HBO(2); < or = 2,468 Torr) stimulates solitary complex neurons. To better define the hyperoxic stimulus, we measured PO(2) in the solitary complex of 300-microm-thick rat medullary slices, using polarographic carbon fiber microelectrodes, during perfusion with media having PO(2) values ranging from 156 to 2,468 Torr. Under control conditions, slices equilibrated with 95% O(2) at barometric pressure of 1 atmospheres absolute had minimum PO(2) values at their centers (291 +/- 20 Torr) that were approximately 10-fold greater than PO(2) values measured in the intact central nervous system (10-34 Torr). During HBO(2), PO(2) increased at the center of the slice from 616 +/- 16 to 1,517 +/- 15 Torr. Tissue oxygen consumption tended to decrease at medium PO(2) or = 1,675 Torr to levels not different from values measured at PO(2) found in all media in metabolically poisoned slices (2-deoxy-D-glucose and antimycin A). We conclude that control medium used in most brain slice studies is hyperoxic at normobaric pressure. During HBO(2), slice PO(2) increases to levels that appear to reduce metabolism.

Animals↗

PubMed2001

Asymmetrical response of p38 kinase activation to volume changes in primary rat astrocytes.

Activation of p38 kinase by osmotic stress has been documented in many cells; however, no report has distinguished the effects of cell volume on p38 activity from the effects of the altered osmotic condition per se. Here we report asymmetrical activation of astrocyte p38 mitogen-activated protein (MAP) kinase in response to volume increases and volume decreases. We separate effects of cell volume changes from the effects of osmotic exposure on p38 activation. Exposure to 400, 500, or 600 mOsm phosphate-buffered saline (PBS) caused cell shrinkage and an osmolality-dependent increase in p38 activity to 175%, 409%, or 518%, respectively, compared with cells maintained in control conditions (290 mOsm). Likewise, hyposmotic conditions ranging from 250 to 57 mOsm PBS caused the same activation of p38 (approximately 300% of the control value within 10 min). The activity in hyposmotic conditions did not diminish over 30 min despite cell volume recovery, indicating a dependence of extracellular osmolality or ionic strength rather than cell volume. Cells that were returned to isosmotic conditions following 30 min in 250, 150, or 57 mOsm PBS shrunk to 73%, 39%, or 26% of the control cell volume, respectively. In these cells, the activity of p38 increased further from approximately 300% of the control values in each hyposmotic condition to as much as 500% of the control activity as a function of the degree of cell shrinkage. Thus, p38 may be activated by cell shrinkage in hyperosmotic or in isoosmotic conditions, indicating reduced cell volume is a more important determinant of this enzyme activity than extracellular osmolality. Our results indicate distinct mechanisms of p38 activation in astrocytes exposed to hyperosmotic or hyposmotic PBS.

Animals↗

PubMed2001

Cigarette smoking increases risk for breast cancer in high-risk breast cancer families.

Most epidemiological studies of cigarette smoking and breast cancer have failed to demonstrate a strong association. Only one study has been performed on women at high genetic risk, and smoking was reported to be a protective factor. To further explore this observation, we examined the association of cigarette smoking with the risk of breast cancer in a historical cohort study of high-risk breast cancer families. A total of 426 families ascertained through a consecutive series of breast cancer patients (probands) between 1944 and 1952 were followed through 1996. Occurrence of breast cancer and detailed smoking histories for sisters, daughters, granddaughters, nieces, and marry-ins were obtained through telephone interviews between 1991 and 1996. Cox proportional hazards regression, accounting for age, birth cohort, and other risk factors, was used to calculate relative risks and 95% confidence intervals (CIs) of breast cancer. All of the models were constructed within strata defined by relationship to the index case (proband), with nonsmokers designated as the referent group. Of the 426 families in the cohort, 132 had at least three incident breast and/or ovarian cancers in the biological relatives at the end of the follow-up period. Among sisters and daughters in these 132 high-risk families, those who ever smoked were at 2.4-fold increased risk of breast cancer (95% CI, 1.2-5.1) relative to never-smokers. No association between breast cancer and smoking was observed among nieces and granddaughters of probands or among marry-ins. When the analysis was restricted to 35 families at highest genetic risk (each containing five breast and/or ovarian cancers), smoking became an even stronger risk factor. Among sisters and daughters, ever-smokers were at 5.8-fold greater risk than nonsmokers (95% CI, 1.4-23.9). Among nieces and granddaughters, the risk of breast cancer associated with smoking was increased 60% (95% CI, 0.8-3.2). These results suggest that smoking may increase risk for breast cancer in families with multiple cases of breast or ovarian cancer, especially those with the strongest apparent familial predisposition.

Adolescent↗

PubMed2000

Risk of breast cancer with oral contraceptive use in women with a family history of breast cancer.

CONTEXT: Oral contraceptive (OC) use is weakly associated with breast cancer risk in the general population, but the association among women with a familial predisposition to breast cancer is less clear. OBJECTIVE: To determine whether the association between OC use and risk of breast cancer is influenced by family history of the disease. DESIGN AND SETTING: Historical cohort study of 426 families of breast cancer probands diagnosed between 1944 and 1952 at the Tumor Clinic of the University of Minnesota Hospital. Follow-up data on families were collected by telephone interview between 1991 and 1996. PARTICIPANTS: A total of 394 sisters and daughters of the probands, 3002 granddaughters and nieces, and 2754 women who married into the families. MAIN OUTCOME MEASURE: Relative risk (RR) of breast cancer associated with history of OC use by relationship to proband. RESULTS: After accounting for age and birth cohort, ever having used OCs was associated with significantly increased risk of breast cancer among sisters and daughters of the probands (RR, 3.3; 95% confidence interval [CI], 1.6-6.7), but not among granddaughters and nieces of the probands (RR, 1.2; 95% CI, 0.8-2.0) or among marry-ins (RR, 1.2; 95% CI, 0.8-1.9). Results were essentially unchanged after adjustment for parity, age at first birth, age at menarche, age at menopause, oophorectomy, smoking, and education. The elevated risk among women with a first-degree family history of breast cancer was most evident for OC use during or prior to 1975, when formulations were likely to contain higher dosages of estrogen and progestins (RR, 3.3; 95% CI, 1.5-7.2). A small number of breast cancer cases (n = 2) limited the statistical power to detect risk among women with a first-degree relative with breast cancer and OC use after 1975. CONCLUSIONS: These results suggest that women who have ever used earlier formulations of OCs and who also have a first-degree relative with breast cancer may be at particularly high risk for breast cancer. Further studies of women with a strong family history who have used more recent lower-dosage formulations of OCs are needed to determine how women with a familial predisposition to breast cancer should be advised regarding OC use today. JAMA. 2000;284:1791-1798.

Adult↗

PubMed2000

Associations of general and abdominal obesity with multiple health outcomes in older women: the Iowa Women's Health Study.

BACKGROUND: Recent clinical guidelines on the health risks of obesity use body mass index (BMI; calculated as weight in kilograms divided by the square of height in meters) and waist circumference, but the waist-hip ratio may provide independent information. METHODS: To assess the joint and relative associations of BMI, waist circumference, and waist-hip ratio with multiple disease end points, we conducted a prospective cohort study of 31,702 Iowa women, aged 55 to 69 years and free of cancer, heart disease, and diabetes, assembled by random sampling and mail survey in 1986. Study end points were total and cause-specific mortality and incidence of site-specific cancers and self-reported diabetes, hypertension, and hip fracture over 11 to 12 years. RESULTS: The waist-hip ratio was the best anthropometric predictor of total mortality, with the multivariable-adjusted relative risk for quintile 5 vs 1 of 1.2 (95% confidence interval, 1.1-1.4), compared with 0.91 (95% confidence interval, 0.8-1.0) for BMI and 1.1 (95% confidence interval, 1.0-1. 3) for waist circumference. The waist-hip ratio was also associated positively with mortality from coronary heart disease, other cardiovascular diseases, cancer, and other causes. The waist-hip ratio was associated less consistently than BMI or waist circumference with cancer incidence. All anthropometric indexes were associated with incidence of diabetes and hypertension. For example, women simultaneously in the highest quintiles of BMI and waist-hip ratio had a relative risk of diabetes of 29 (95% confidence interval, 18-46) vs. women in the lowest combined quintiles. CONCLUSION: The waist-hip ratio offers additional prognostic information beyond BMI and waist circumference.

Abdomen↗

PubMed2000

Twinship and risk of postmenopausal breast cancer.

BACKGROUND: Intrauterine exposure to high levels of endogenous estrogens has been hypothesized to increase the risk of breast cancer. Because estrogens and other pregnancy hormones are substantially elevated in twin pregnancies, and possibly more so in dizygotic twin pregnancies, we evaluated the association between aspects of twin membership (i.e., belonging to a twin pair) and the risk of breast cancer. METHODS: In a cohort of 29 197 postmenopausal Iowa women with no prior diagnosis of cancer (except for nonmelanoma skin cancer), breast cancer risk factors were determined by use of a mailed questionnaire in 1986 (baseline); twin membership, sex of the twin, and zygosity were determined by use of a follow-up questionnaire in 1992. RESULTS: Within the cohort, 1.8% (n = 538) of the women reported being a twin; of these, 24% (n = 130) were monozygotic twins, 63% (n = 337) were dizygotic twins, and 13% (n = 71) did not know their zygosity. From 1986 through 1996, 1230 breast cancers in the cohort were ascertained by linkage to the Iowa Cancer Registry. Compared with singletons, women who belonged to a twin pair were at elevated risk of breast cancer (multivariate-adjusted risk ratio [RR] = 1.72; 95% confidence interval [CI] = 1.22-2.42), with adjustment for educational level, family history of breast cancer, height, body mass index, body fat distribution, age at menarche, age at first live birth, use of hormone replacement therapy, and alcohol use. Multivariate-adjusted risk was elevated (in comparison with singletons) if the sex of the other twin was female (RR = 1.82; 95% CI = 1.20-2.75); however, this risk was limited to female dizygotic twins (RR = 2.14; 95% CI = 1. 21-3.79), since no excess risk was evident for monozygotic twins (RR = 1.04; 95% CI = 0.43-2.50). The risk to women with a male twin was also elevated (RR = 1.49; 95% CI = 0.80-2.78) in comparison with singletons, but this estimate was not statistically significant. CONCLUSIONS: This cohort study lends further support to the theory that there are important intrauterine influences on carcinogenesis of the breast.

Aged↗

PubMed2000

Identification of the nitrogen-based blister agents bis(2-chloroethyl)methylamine (HN-2) and tris(2-chloroethyl)amine (HN-3) and their hydrolysis products on soil using ion trap secondary ion mass spectrometry.

The nitrogen blister agents HN-2 (bis(2-chloroethyl)methylamine) and HN-3 (tris(2-chloroethyl)amine) were directly analyzed on the surface of soil samples using ion trap secondary ion mass spectrometry (SIMS). In the presence of water, HN-1 (bis(2-choroethyl)ethylamine), HN-2 and HN-3 undergo hydrolysis to form N-ethyldiethanolamine, N-methyldiethanolamine and triethanolamine (TEA), respectively; these compounds can be readily detected as adsorbed species on soil particles. When soil samples spiked with HN-3 in alcohol were analyzed, 2-alkoxyethylamine derivatives were observed on the sample surfaces. This result shows that nitrogen blister agents will undergo condensation reactions with nucleophilic compounds and emphasizes the need for an analytical methodology capable of detecting a range of degradation and condensation products on environmental surfaces. The ability of ion trap SIMS to isolate and accumulate ions, and then perform tandem mass spectrometric analysis improves the detection of low-abundance surface contaminants and the selectivity of the technique. Utilizing these techniques, the limits of detection for HN-3 were studied as a function of surface coverage. It was found that HN-3 could be detected at a surface coverage of 0.01 monolayer, which corresponds to 20 ppm (mass/mass) for a soil having a surface area of 2.2 m(2) g(-1). TEA, the exhaustive hydrolysis product of HN-3, was detected at a surface coverage of 0.001 monolayer, which corresponds to 0.86 ppm.

3,4-Methylenedioxyamphetamine↗

PubMed2000

Osmotic sensitivity of taurine release from hippocampal neuronal and glial cells.

Taurine transport is important for volume regulation of cultured neurons and astroglial cells. Both cell types utilize similar mechanisms for taurine accumulation and efflux. However, taurine lost from cerebellar Purkinje cells in vivo is accumulated by adjacent astrocytes during hypoosmotic hyponatremia. To examine mechanisms for transfer of taurine between cell types, we measured relative sensitivities of taurine loss from cultured neurons and astrocytes. Primary cultures of hippocampal neurons and astrocytes were grown from embryonic and neonatal rat brain, respectively. Neurons were used after 10-14 days in culture. Astrocytes were used after 14 days in culture and were grown in the same culture medium used for neurons for 3 days prior to experimentation. Cells were incubated at 37 degrees C for 30 min in isoosmotic (290 mOsm) phosphate-buffered saline (PBS). The PBS was then changed to fresh isoosmotic or to hypoosmotic PBS (270 mOsm or 250 mOsm), made by reducing the NaCl concentration. Cell volume and taurine content were determined immediately before hypoosmotic exposure or 3, 15, or 30 min later. In isoosmotic PBS, astrocytes contained 162 +/- 18 nmol taurine/mg protein (mean +/- SEM), equivalent to an intracellular concentration of 30.2 +/- 2.1 mM. No taurine loss was detectable after 3 or 15 min in either hypoosmotic PBS, but after 30 min in 270 or 250 mOsm PBS, astrocyte taurine was reduced by 8.0% or 22.2%, respectively. Neurons initially contained 114 +/- 13 nmol taurine/mg protein, equivalent to an intracellular taurine concentration of 22.2 +/- 2.5 mM. After 3 min of exposure to 270 or 250 mOsm PBS, the cells had lost 17 +/- 5% or 25 +/- 4% of their taurine content, respectively. Cell volumes of each cell type were similarly affected by hypoosmotic exposure. We conclude that taurine loss from cultured hippocampal neurons is more sensitive to osmotic swelling than taurine loss from cultured hippocampal astrocytes. This characteristic, if present in cells of the hippocampus in vivo, could lead to net transfer of taurine from neurons to glial cells during pathological conditions which cause cell swelling.

Animals↗

PubMed2000

Characterization of VX on concrete using ion trap secondary ionization mass spectrometry.

The nerve agent VX (O-ethyl S-2-diisopropylaminoethyl methyl phosphonothiolate) was analyzed on the surface of concrete samples using an ion trap secondary ion mass spectrometer (IT-SIMS). It was found that VX could be detected down to an absolute quantity of 5 ng on a concrete chip, or to a surface coverage of 0.0004 monolayers on crushed concrete. To achieve these levels of detection, the m/z 268-->128 ion fragmentation was measured using MS2, where m/z 268 corresponds to [VX + H]+, and 128 corresponds to a diisopropylvinylammonium isomer, that is formed by the elimination of the phosphonothiolate moiety. Detection at these levels was accomplished by analyzing samples that had been recently exposed to VX, i.e., within an hour. When the VX-exposed concrete samples were aged, the SIMS signature for intact VX had disappeared, which signaled the degradation of the compound on the concrete surface. The VX signature was replaced by ions which are interpreted in terms of VX degradation products, which appear to be somewhat long lived on the concrete surface. These compounds include ethylmethylphosphonic acid (EMPA), diisopropyl taurine (DIPT), diisopropylaminoethanethiol (DESH), bis(diisopropylaminoethane) disulfide [(DES)2], and a particularly tenacious compound that may correspond to diisopropylvinylamine (DIVA), or an isomer thereof. It was found that the thiolamine-derived degradation products DIPT, DESH, and (DES)2 were removed with isopropyl alcohol extraction. However, the DIVA-related degradation product was observed to strongly adhere to the concrete surface for longer than one week. Although quantitation was not possible in this set of experiments, the results clearly show the rapid degradation of VX on concrete, as well as the surface sensitivity of the IT-SIMS for intact VX and its adsorptive degradation products.

Chemical Warfare Agents↗

PubMed2000

Perception of genetic risk among genetic counselors.

A mailed survey of female prenatal genetic counselors, obstetric nurses, and high school biology teachers was conducted to determine if these groups hold different attitudes toward genetic risk and to investigate the extent to which any differences result from the effect of different professional experiences. In this study, the participants were 166 genetic counselors, 116 obstetric nurses, and 78 biology teachers (n=360). Survey participants completed a written questionnaire designed to assess their numeric estimate of the empiric risk for birth defects/genetic problems, their subjective perception of this risk, and their personal use of prenatal diagnosis. Genetic counselors were found to be less likely than the other groups to consider the frequency of birth defects/genetic problems as rare and were 10 times more likely than nurses and 8 times more likely than teachers to have had prenatal diagnosis. Furthermore, more than half of the prenatal diagnosis procedures had by genetic counselors were not medically indicated. These results suggest that genetic counselors have an increased perception of genetic risks relative to nurses or teachers. Possible explanations for this funding are discussed, and the potential role of discordant risk perception in creating biases in genetic counseling process is explored.

Attitude↗