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Biomedical subjects

D Anderson

Publications and source records attributed to D Anderson.

At least 325 records · Page 18Linked to original sources
PubMed1993

Two studies of reported pretraumatic stressors' effect on posttraumatic stress disorder severity.

We contrasted in two studies the effects of military trauma on Vietnam veterans who reported high and low premilitary stress. In the first, we administered the Posttraumatic Stress Disorder Interview (PTSD-I), a premilitary modification of the Social Readjustment Rating Scale, and the Military Stress Scale to hospitalized veterans. Premilitary stress appeared to reduce the impact of combat on several trauma-reexperiencing ratings, although the relevant evidence was inconsistent. In the second study, the premilitary stress main effects and the premilitary stress/combat interactions on four PTSD-I factors were nonsignificant. Thus, the severities of most PTSD symptoms increased with trauma intensity, but not with milder premilitary stress. The inconsistent data on the impact of pretraumatic stress on the trauma severity/PTSD relationships suggest further study.

Adult↗
PubMed1993

The N-terminal region of GAP regulates cytoskeletal structure and cell adhesion.

Ras GTPase activating protein (GAP) possesses a C-terminal domain that interacts with GTP-bound Ras, and an N-terminal region containing two SH2 domains and an SH3 domain. In addition to its association with Ras, GAP binds stably to autophosphorylated beta PDGF receptors, and to two cytoplasmic phosphoproteins: p62, an RNA binding protein, and p190, which possesses GAP activity towards small guanine nucleotide binding proteins in the Rho/Rac family. To define the region of GAP that mediates these interactions with cellular phosphoproteins, and to investigate the biological significance of these complexes, a truncated GAP polypeptide (GAP-N) containing residues 1-445 was stably expressed in Rat-2 fibroblasts. GAP-N contains the SH2 and SH3 domains, but lacks the Ras GTPase activating domain. Stimulation of cells expressing GAP-N with PDGF induced association of GAP-N with the beta PDGF receptor, and phosphorylation of GAP-N on tyrosine, consistent with the notion that GAP SH2 domains direct binding to the autophosphorylated beta PDGF receptor in vivo. GAP-N bound constitutively to p190 in both serum-deprived and growth factor-stimulated cells. This GAP-N-p190 complex had Rho GAP activity in vitro. The expression of GAP-N in Rat-2 cells correlated with changes in the cytoskeleton and in cell adhesion, typified by the disruption of action stress fibres, a reduction in focal contacts, and an impaired ability to adhere to fibronectin. These results suggest that the N-terminal domain of GAP can direct interactions with cellular phosphoproteins in vivo, and thereby exert an effector function which modulates the cytoskeleton and cell adhesion.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗
PubMed1993

The modulating effects of antioxidants in rat embryos and Sertoli cells in culture.

The male and female reproductive systems are targets for the toxicity of a wide range of compounds. There is a paucity of information regarding the modulating effects of antioxidants in such systems. Enzymically generated oxygen radicals have been shown to be toxic and/or mutagenic in a variety of in vitro test systems. It is known that vitamins C and E can modify responses in such systems. Malformations and growth reductions have been observed in whole rat embryo cultures in this laboratory after treatment with the oxygen radical generating system of xanthine/xanthine oxidase. Groups of 9.5-day-old rat embryos were treated with this system with or without vitamin C or E. Vitamin C at the doses given totally abolished neural suture defects while vitamin E only partially did so. Vitamins C and E administered alone had no effect on the embryos. Germ cell detachment has been shown to occur in mixed cultures of Sertoli and germ cells in response to some known in vivo testicular toxins. Such cultures were also treated with the oxygen radical generating system of xanthine/xanthine oxidase. There was an increase in germ cell detachment with this treatment which was reduced by vitamin C but not by vitamin E at the doses administered. These findings would suggest that vitamin supplementation could protect somatic cells of reproductive systems against toxins that act through oxygen radical mechanisms.

Animals↗
PubMed1993

Antiviral effects of different CD4-immunoglobulin constructs against HIV-1 and SIV: immunological characterization, pharmacokinetic data and in vivo experiments.

The CD4 cell surface antigen belongs to the immunoglobulin superfamily and is the primary receptor for the human immunodeficiency virus 1 (HIV-1). The high affinity interaction between HIV-1 and CD4 is mediated by the viral envelope glycoprotein gp120. Recombinant soluble CD4 (rsCD4) has been shown in vitro to be an effective inhibitor of HIV-1 and HIV-2 propagation in lymphoid cells. A variety of antibody-like molecules were constructed, consisting of different parts of the extracellular domain of CD4 fused to immunoglobulin constant regions. The fusion proteins were expressed in mammalian cell lines and purified via affinity chromatography. The specificity and anti-viral effects of the different CD4-immunoglobulin constructs against HIV were analysed by different immunological tests, i.e., immunofluorescence, neutralisation and in vitro assays. In pharmacokinetic studies, differences were found in serum half-life between the four- and two-domain CD4 constructs in cynomolgus monkeys and between glycosylated and deglycosylated CD4-Fc constructs in rabbits. In two in vivo experiments using the four-domain CD4-Fc in SIV-infected macaques, no beneficial effects were observed.

Animals↗
PubMed1993

Monitoring of exposure to styrene oxide by GC-MS analysis of phenylhydroxyethyl esters in hemoglobin.

Styrene oxide, which is the genotoxically active metabolite of styrene, reacts in vivo with carboxylic acid residues in hemoglobin forming phenylhydroxyethyl esters. Mild alkali hydrolysis cleaves these ester adducts, yielding styrene glycol, which in human blood labelled in vitro with 14C-styrene oxide accounted for 15% of the total radioactivity covalently bound to the protein. A quantitative assay procedure has been developed for measuring the base released styrene glycol in globin. The method utilizes solvent extraction followed by trimethylsilyl ether derivatization and separation and quantitation by capillary gas chromatography with selective ion recording mass spectrometry. Globin labelled in vitro with d8-styrene oxide was used as the internal standard. The method was used to establish a dose-response relationship in rats given single i.p. doses of styrene oxide (83.3-833 mumol/kg body wt). The method, which allows quantitation of the adducts down to levels of 15 pmol/g globin, has the potential to act as a dosimeter for industrial workers exposed to styrene or styrene oxide.

Animals↗
PubMed1993

The effect of simultaneous exposure to bromodeoxyuridine and methyl methanesulphonate on sister-chromatid exchange frequency in cultured human lymphocytes.

Assessment of genotoxicity in cultured cells or in experimental animals through the measurement of sister-chromatid exchanges (SCEs) commonly requires their simultaneous exposure to both the test agent and bromodeoxyuridine (BrdUrd). This dual exposure could lead to modified responses because of either synergistic or antagonistic interactions. Differences in protocol may also have their effect. There is, for example, time for DNA repair to take place in protocols in which there is separate exposure to the test agent and BrdUrd, such as human genetic monitoring studies. In this study, human lymphocyte cultures have been used to investigate the effect of the duration of simultaneous exposure to the mutagen methyl methanesulphonate (MMS) and to BrdUrd on SCE incidence. There was a direct relationship between SCE frequency and the time of simultaneous exposure to MMS and BrdUrd that was not dependent on either the total culture time or the total time of exposure to BrdUrd. This suggestion of an interaction between MMS and BrdUrd in inducing SCEs has important implications for the interpretation of SCE data in both experimental and human monitoring studies.

Analysis of Variance↗
PubMed1993

Molecular analysis of mutation at the hprt locus of Chinese hamster V79 cells induced by ethyl methanesulphonate and mitomycin C.

Mutations at the hprt locus of Chinese hamster V79 cells were induced by treatment with ethyl methanesulphonate (EMS), considered primarily a point mutagen and mitomycin C (MMC), a potent clastogen. EMS gave a dose-dependent induction of mutants while MMC induced a poor mutagenic response. Mutations were analysed using Southern and Northern blotting. Analysis of 9 EMS-induced and 4 spontaneous mutants yielded no detectable alterations in the hprt locus after digestion of DNA with 6 restriction enzymes. Mutants without detectable changes carried presumptive point mutations. In contrast, 4 out of 12 MMC-induced mutants had detectable alterations. 2 of these appeared to have lost the entire hprt gene while the other 2 had probable partial deletions. For these 4 deletion mutants no hprt mRNA was detected. 3 MMC-induced and 1 EMS-induced mutants had reduced levels of hprt mRNA. All the other mutants showed normal levels of hprt mRNA and the message detected was always of the correct size. It is suggested that the poor mutagenic response induced by MMC may be due to the lethal nature of large deletions involving both the hemizygous hprt locus and adjacent essential genes. This may lead to an underestimate of the mutagenicity of clastogenic agents such as MMC in the V79 HPRT mutation assay.

Animals↗
PubMed1993

Childhood psychological trauma and chronic refractory low-back pain.

OBJECTIVE: To examine the correlation between childhood psychological trauma(s) and refractory back pain in patients with and patients without prior spine surgery. DESIGN: Retrospective chart review survey of 101 consecutive patients who had undergone multidisciplinary evaluation for refractory back pain. SETTING: Private practice, tertiary care spine center. MAIN OUTCOME MEASURES: Each psychological risk factor (physical abuse, sexual abuse, emotional neglect or abuse, abandonment, and chemically dependent caregiver) was rated as present or absent. Spinal pathology was graded as significant or not significant. RESULTS: There were 56 patients with failed back surgery syndrome, 28 men and 28 women, with a mean age of 43 and mean pain duration of 45 months. There were 45 patients with no prior surgery, 26 men and 19 women, with a mean age of 43 and mean pain duration of 33 months. In the failed back surgery syndrome group, 27 (48%) had three or more risks and 39 (70%) had two or more. When the 12 patients with significant pathology are not considered, 24 of the remaining 44 (55%) patients had three or more risks. In the group with no prior surgery, 26 (58%) had three or more risks and 38 (84%) had two or more. When the five patients with significant pathology are not considered, 24 (60%) had three or more risks. CONCLUSIONS: Multiple childhood psychological traumas may predispose a person to chronic low back pain. In patients in this setting with refractory low back pain with or without prior lumbar spine surgery, three or more childhood psychological risk factors are prevalent, especially in patients with minimal structural pathology.

Adult↗
PubMed1993

Effect of entrainment time on pulmonary deposition of cigarette smoke in dogs.

Chronic inhalation of tobacco smoke can produce a nonuniform pattern of lung disease, with apical (nondependent) areas affected more often and more severely than other lung regions. This localized tissue damage might be the result of uneven deposition of inhaled smoke aerosol. There is some evidence to suggest that the way in which an aerosol is inhaled can influence its deposition in the lung. This study sought to determine the effects of entrainment timing on the deposition of tobacco smoke in the lung. Anesthetized mechanically ventilated dogs (n = 14) inhaled 35-ml boluses of 14C-labeled mainstream cigarette smoke once per minute in either a supine or erect posture. Boluses were entrained at the start of inspiration (group 1) or at midinspiration (group 2). Lungs were removed, sectioned, and assayed for 14C. Group 1 lungs experienced deposition in regions distant from the tracheal axis, with peripheral lung units averaging twice the deposition of 14C as central units. Group 2 lungs had a more uniform 14C distribution pattern. Early smoke entrainment favored peripheral deposition. One explanation for this finding is that peripheral lung units may have shorter time constants, thus filling sooner and more completely than those located centrally.

Aerosols↗
PubMed1993

Cytomegalovirus infection and pneumonitis. Impact after isolated lung transplantation. Washington University Lung Transplant Group.

Using aggressive surveillance of blood, bronchoalveolar lavage (BAL) fluid, and lung tissue, we sought to determine the incidence of cytomegalovirus (CMV) pneumonitis in isolated lung transplant recipients and to characterize its impact on pulmonary function, chronic rejection, and survival. Forty-six lung transplant recipients who survived greater than 30 days had prospective documentation of CMV infection in blood and BAL fluid and regular surveillance with transbronchial lung biopsy. CMV infection was documented in 92% of patients who were D-/R+, D+/R+, or D+/R-, and the incidence of histologically confirmed CMV pneumonitis among these patients was 75%. No D-/R- patient experienced CMV infection or disease. D+/R- patients experienced more frequent and severe episodes, and ganciclovir prophylaxis during the first 2 wk was not useful. CMV pneumonitis was accompanied by detectable radiographic changes in less than one third of cases. The detection of CMV in BAL fluid was not predictive of CMV pneumonitis on biopsy, except in D+/R- patients during the first 90 days after transplantation. There was no evidence of an adverse impact because of CMV infection on pulmonary function during the first year after transplantation. A relationship between CMV infection and bronchiolitis obliterans could not be documented; however, D+/R- patients had higher morbidity and a trend toward lower survival. In a multivariate analysis, D+/R- status was an independent predictor of death.

Adult↗
PubMed1993

Variability in chromosome aberrations, sister chromatid exchanges, and mitogen-induced blastogenesis in peripheral lymphocytes from control individuals.

Confidence in results from monitoring genetic end points in environmentally or occupationally exposed individuals can be improved with knowledge of the normal variability of changes in genetic end points in the general population. Confounding effects can be determined, and study interpretation can be improved by correlation of this variability with various lifestyle factors such as sex and age, smoking and drinking habits, viral infections, exposure to diagnostic X-rays, etc. Eight blood samples were taken from each of 24 male and 24 female volunteers over a period of 2 years. Questionnaires pertaining to lifestyle were completed at the time of each sampling. Whole blood was cultured and slides prepared for chromosome aberration (CA) or sister chromatid exchange (SCE) analysis. Separated mononuclear cells were cultured with a range of phytohemagglutinin concentrations, and the maximum level of mitogen-induced blastogenesis was determined by measurement of [3H]thymidine uptake. There was a significant effect of both year and season of sampling for all three end points. Because there was no consistent pattern in 2 successive years, effects were thought to be independent of season. No significant effects in any of the three end points were found with respect to sex or age nor any of the other lifestyle factors, although SCE frequency and mitogen-induced blastogenesis were nearly always higher in females than in males. These results point to the need for concurrent sampling of controls with exposed populations.

Cells, Cultured↗
PubMed1993

Identification of endogenous electrophiles by means of mass spectrometric determination of protein and DNA adducts.

Monitoring exposure to alkylating agents may be achieved by quantitatively determining the adduct levels formed with nucleic acids and/or proteins. One of the most significant results arising from the application of this approach has been the discovery in control populations of "background" levels of alkylated nucleic acid bases or alkylated proteins, in particular hemoglobin (Hb). In the case of Hb, a wide variety of such adducts have been detected and quantitated by mass spectrometric techniques, with methylated, 2-carboxyethylated, and 2-hydroxyethylated modifications being most abundant. Although the source of these alkylation products is unknown, both endogenous and exogenous sources may be proposed. We have recently confirmed the presence of the N-terminal hydroxyethylvaline adduct in control human Hb using tandem mass spectrometry (MS-MS) and have now established background levels using GC-MS in more than 70 samples. Smoking raises the levels of the adduct up to 10-fold and occupational exposure to ethylene oxide up to 300-fold. Background levels of alkylated nucleic acids may be studied by analysis of N7-alkylated guanine or N3-alkylated adenine, which are excised from nucleic acids after their formation and are excreted in urine. Although the presence of some of these urinary constituents may be accounted for by their natural occurrence in RNA or diet, the endogenous or exogenous source of others is unknown. Quantitative methods using MS-MS have now been developed for five of the observed urinary alkylguanines [N7-methyl-, N2-methyl-, N2-dimethyl-, N7-(2-hydroxyethyl)-, and N2-ethylguanine].(ABSTRACT TRUNCATED AT 250 WORDS)

Alkylating Agents↗
PubMed1993

Male-mediated F1 effects in mice exposed to 1,3-butadiene.

We examined the effects on dominant lethality and the incidence of fetal abnormalities of acute and subchronic exposure of male mice by inhalation to the industrial monomer 1,3-butadiene. Investigation of the effect on tumour incidence in surviving offspring is still in progress. In the acute study, CD-1 mice were exposed to atmospheres containing 0 (n = 25), 1250 (n = 25) or 6250 ppm (n = 50) for 6 h, and each male was caged five days later for one week with two untreated virgin females. One of the females was killed humanely on day 17 of gestation. The other was allowed to deliver and rear her litter; the litters are being monitored for life. The killed female was examined for the number of live fetuses, the number of post-implantation deaths (early and late) and the number and type of any gross malformations. In the subchronic study, males were exposed to 0 (n = 25), 12.5 (n = 25) or 1250 ppm (n = 50) for 6 h per day on 5 days per week for 10 weeks and then mated immediately. Mating and observation were conducted as in the acute study. Acute exposure to butadiene resulted in only a small decrease in implantations; after 10 weeks' subchronic exposure to either the high or the low concentration, however, a wide variety of statistically significant effects was seen. At 1250 ppm, the number of implantations was reduced, dominant lethal mutations were induced, and the incidences of early and late deaths were increased; some of the live fetuses had abnormalities. The low dose also increased the frequency of abnormalities and late deaths, but it did not affect the number of early deaths. Thus, butadiene is mutagenic in the germ cells of male mice, as shown by the induction of dominant lethality at 1250 ppm, and the frequencies of late deaths and congenital abnormalities appear to be increased at the subchronic level of 12.5 ppm.

Abnormalities, Drug-Induced↗
PubMed1993

Prevalence of maternal drug use near time of delivery.

Prenatal substance abuse is a problem of growing concern because of the negative effects it has on the health of the woman and developing fetus. To evaluate the prevalence of this problem in our community, anonymous toxicology studies were performed on 1,003 maternal urines. Samples were connected at time of delivery and selection bias was addressed. Results indicated that cocaine or marijuana metabolites were present in 4% of all urines. Among clinic patients, 12.4% tested positive (7.3% cocaine; 5.1% marijuana) and 1.3% tested positive among private patients (0.7% cocaine; 0.7% marijuana). Poor prenatal care was positively associated with substance use regardless of clinic or private care: 50% of those with fewer than three prenatal visits tested positive for cocaine or marijuana compared with 2% of those with more than three prenatal visits. Maternal age < 18 years did not predict substance use. Program planning in Connecticut should progress with these data in mind.

Adolescent↗
PubMed1993

Moderate hypercapnia: cardiovascular function and nitrogen elimination.

Elevated carbon dioxide concentrations frequently encountered in diving operations may have cardiovascular effects. If so, changes in nitrogen loading and elimination may be induced. To study this possibility, whole body nitrogen elimination rates were determined using a rebreathing apparatus and gas chromatographic measurement of N2 in expired gas in six subjects as they breathed mixtures of 3 and 5% CO2 with 21% O2 and a balance of Ar for 125 min. No significant differences were observed among mean N2 yields, which were 815 ml (95% confidence interval +/- 51 ml), 831 ml (+/- 38 ml), and 845 ml (+/- 57 ml) for 0, 3, and 5% CO2 mixtures, respectively. Simultaneous measurements of heart rate showed a significant increase while breathing 5% CO2 as compared to 3 and 0% CO2. The increases in heart rate were not accompanied by any significant change in cardiac output, mean arterial pressure, or tissue perfusion. We conclude that at these levels of hypercarbia, tissue perfusion is not influenced enough to cause any changes in whole-body N2 elimination.

Adult↗
PubMed1993

Comparison of psychologic and physiologic functioning between patients with masticatory muscle pain and matched controls.

This study explored the physiologic and psychologic distinctions between masticatory muscle pain patients and age and sex-matched normal controls. Subjects completed several standardized psychologic tests. They then underwent a laboratory stress profile evaluation to obtain physiologic measures (EMG, heart rate, systolic and diastolic blood pressure) under conditions of rest, mental stress, and relaxation. The pain patients reported greater anxiety, especially cognitive symptoms, and feelings of muscle tension than did the controls. Under stress, pain patients had higher heart rates and systolic blood pressure than the controls. Electromyogram activity in the masseter regions was not significantly different between the pain and control group. The results are discussed in terms of the likely mechanisms that might account for the observed differences between masticatory pain patients and normal subjects.

Adult↗