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Biomedical subjects

S Warren

Publications and source records attributed to S Warren.

At least 37 records · Page 2Linked to original sources
PubMed1997

Emotion regulation in mother-child narrative co-construction: associations with children's narratives and adaptation.

The associations were studied between early mother-child co-construction of a separation-reunion narrative and children's concurrent and later (a) emotion narratives and (b) behavior problems. Fifty-one children and their mothers were observed during a co-construction task when the children were age 4 1/2. At ages 4 1/2 and 5 1/2, children's narratives were elicited using the MacArthur Story-Stem Battery (MSSB), and mothers completed the Child Behavior Checklist. Results showed that children who were more emotionally coherent during the co-constructions had MSSB narratives that were more coherent, had more prosocial themes, and had fewer aggressive themes at ages 4 1/2 and 5 1/2. Moreover, such children had fewer behavior problems at both ages. The relations between narrative processes and emotion regulation are discussed.

Adult↗
PubMed1997

Interaction between cortisol and tumour necrosis factor with concurrent resistance and endurance training.

OBJECTIVE: To determine the effect of concurrent resistance and endurance training on tumor necrosis factor alpha (TNF alpha), urinary free cortisol, strength [one-repetition maximum (1 RM)], and maximal oxygen consumption (Vo2max). DESIGN: Randomized control trial of 12 weeks' duration. SETTING: University of Alberta, Edmonton, Alberta, Canada. PARTICIPANTS: Forty-five healthy female (n = 18) and male (n = 27) subjects who had not formally trained for at least 6 months prior to the study but were physically active. The mean +/- SD age, height, and body mass for all subjects were 22.3 +/- 3.3 years, 1.76 +/- 9.32 m, and 73.4 +/- 11.6 kg, respectively. INTERVENTION: The subjects were randomly assigned to four groups: strength training only (S), n = 10; endurance training only (E), n = 11; combined strength and endurance training (SE), n = 13; and a control group (C), n = 10. The S and E groups performed progressively overloaded training sessions three times per week for 12 weeks. The SE group completed the same strength and endurance training programs on different days (i.e., 6 days/week) for 12 weeks. MAIN OUTCOME MEASURES: Serum levels of TNF alpha, urinary free cortisol, 1 RM, and Vo2max were measured before and after 6 and 12 weeks of training. RESULTS: Significant increases in leg press and knee extension 1 RM occurred after training in both S and SE groups, but the relative gains in knee extension 1 RM were greater in the S group. Similar increases in Vo2max were observed in groups E and SE (p < 0.05). Cortisol was significantly increased in the SE group for women and decreased in the E group for men after training. TNF alpha was significantly elevated in the women of group E after training. No correlation was observed between urinary free cortisol and TNF alpha with training. CONCLUSION: These results indicate that a partial interference effect of compromised strength gains in unilateral knee extension of the men occurred after concurrent strength and endurance training that could not be attributed to an interaction between cortisol and TNF alpha in response to this type of exercise.

Adult↗
PubMed1997

Children's narrative representations of mothers: their development and associations with child and mother adaptation.

We investigated associations between children's representations of mothers in their play narrative and measures of children's and mothers' socioemotional adaptation, and explored the development of these representations between the ages of 4 and 5 years. Fifty-one children were interviewed using the MacArthur Story-Stem Battery to obtain their narrative representations of mothers. Positive, Negative, and Disciplinary representation composites were generated. Children who had more Positive and Disciplinary representations and fewer Negative representations had fewer behavior problems and their mothers reported less psychological distress. In addition, 5-year-olds had more Positive and Disciplinary representations and fewer Negative representations than did 4-year-olds, and there was moderate stability in individual differences in children's representations of mothers across the 2 ages. The results add an important dimension to research on parent-child relationships--that of children's perspectives on these relationships.

Adaptation, Psychological↗
PubMed1997

Preschoolers face moral dilemmas: a longitudinal study of acknowledging and resolving internal conflict.

Following on from research that indicated significant moral internalisations by age 3, using a play narrative approach in which children were asked to complete story stems describing a range of moral dilemmas, the purpose of this study was to replicate the results, extend them with longitudinal information and assess the child's developing capacities to acknowledge both sides of moral dilemmas and resolve them in a prosocial way. Fifty-one children were presented with three enacted story stems describing moral dilemmas as they might occur in everyday life. Story completions were obtained from children at ages 3, 4, and 5 and were coded for the level of acknowledgement of the dilemmas and the degree of prosocialness involved in story resolution. Results included the following: firstly, some children acknowledged the dilemmas and resolved them prosocially as early as age 3; secondly, the ability to acknowledge dilemmas and resolve them improved with age; and thirdly, children showed a greater capacity to acknowledge dilemmas with support from an examiner. The implications of these findings for our understanding early moral development are discussed, along with questions pointing to new research.

Child Development↗
PubMed1996

The neurological mouse mutations jittery and hesitant are allelic and map to the region of mouse chromosome 10 homologous to 19p13.3.

Jittery (ji) is a recessive mouse mutation on Chromosome 10 characterized by progressive ataxic gait, dystonic movements, spontaneus seizures, and death by dehydration/starvation before fertility. Recently, a viable neurological recessive mutation, hesitant, was discovered. It is characterized by hesitant, unco-ordinated movements, exaggerated stepping of the hind limbs, and reduced fertility in males. In a complementation test and by genetic mapping we have shown here that hesitant and jittery are allelic. Using several large intersubspecific backcrosses and intercrosses we have genetically mapped ji near the marker Amh and microsatellite markers D10Mit7, D10Mit21, and D10Mit23. The linked region of mouse Chromosome 10 is homologous to human 19p13.3, to which several human ataxia loci have recently been mapped. By excluding genes that map to human 21q22.3 (Pfkl) and 12q23 (Nfyb), we conclude that jittery is not likely to be a genetic mouse model for human Unverricht-Lundborg progressive myoclonus epilepsy (EPM1) on 21q22.3 nor for spinocerebellar ataxia II (SCA2) on 12q22-q24. The closely linked markers presented here will facilitate positional cloning of the ji gene.

Alleles↗
PubMed1996

Costimulation enhances the active immunotherapy effect of recombinant anticancer vaccines.

Activation of T lymphocytes in the absence of a costimulatory signal can result in anergy or apoptotic cell death. Two molecules capable of providing a costimulatory signal, B7-1 (CD80) and B7-2 (CD86), have been shown to augment the immunogenicity of whole-tumor cell vaccines. To explore a potential role for costimulation in the design of recombinant anticancer vaccines, we used lacZ-transduced CT26 as an experimental tumor and beta-galactosidase (beta-gal) as the model tumor antigen. Attempts to augment the function of a recombinant vaccinia virus (rVV) expressing beta-gal by admixture with rVV expressing murine B7-1 were unsuccessful. However, a double recombinant vaccinia virus engineered to express both B7-1 and the model antigen beta-gal was capable of significantly reducing the number of pulmonary metastases when administered to mice bearing tumors established for 3 or 6 days. Most important, the double recombinant vaccinia virus prolonged the survival of tumor-bearing mice. These effects were antigen specific. The related costimulatory molecule B7-2 was found to have a similar, although less impressive enhancing effect on the function of a rVV expressing beta-gal. Thus, the addition of B7-1 and, to a lesser extent, B7-2 to a rVV encoding a model antigen significantly enhanced the therapeutic antitumor effects of these poxvirus-based, therapeutic anticancer vaccines.

Animals↗
PubMed1996

A full genome search in multiple sclerosis.

The aetiology of multiple sclerosis (MS) is uncertain. There is strong circumstantial evidence to indicate it is an autoimmune complex trait. Risks for first degree relatives are increased some 20 fold over the general population. Twin studies have shown monozygotic concordance rates of 25-30% compared to 4% for dizygotic twins and siblings. Studies of adoptees and half sibs show that familial risk is determined by genes, but environmental factors strongly influence observed geographic differences. Studies of candidate genes have been largely unrewarding. We report a genome search using 257 microsatellite markers with average spacing of 15.2 cM in 100 sibling pairs (Table 1, data set 1 - DS1). A locus of lambda>3 was excluded from 88% of the genome. Five loci with maximum lod scores (MLS) of >1 were identified on chromosomes 2, 3, 5, 11 and X. Two additional data sets containing 44 (Table 1, DS2) and 78 sib pairs (Table 1, DS3) respectively, were used to further evaluate the HLA region on 6p21 and a locus on chromosome 5 with an MLS of 4.24. Markers within 6p21 gave MLS of 0.65 (non-significant, NS). However, D6S461, just outside the HLA region, showed significant evidence for linkage disequilibrium by the transmission disequilibrium test (TDT), in all three data sets (for DS1 chi2 = 10.8, adjusted P < 0.01)(DS2 and DS3 chi2 = 10.9, P < 0.0005), suggesting a modest susceptibility locus in this region. On chromosome 5p results from all three data sets (222 sib pairs) yielded a multipoint MLS of 1.6. The results support genetic epidemiological evidence that several genes interact epistatically to determine heritable susceptibility.

Chromosome Mapping↗
PubMed1996

Antiviral efficacy in vivo of the anti-human immunodeficiency virus bicyclam SDZ SID 791 (JM 3100), an inhibitor of infectious cell entry.

SID 791, a bicyclam inhibiting human immunodeficiency virus (HIV) replication in vitro by blocking virus entry into cells, is an effective inhibitor of virus production and of depletion of human CD4+ T cells in HIV type 1-infected SCID-hu Thy/Liv mice. Steady levels of 100 ng of SID 791 or higher per ml in plasma resulted in statistically significant inhibition of p24 antigen formation. Daily injections of SID 791 caused a dose-dependent decrease in viremia, and this inhibition could be potentiated by coadministration of zidovudine or didanose. The present study suggests that SID 791 alone or in combination with licensed antiviral agents may decrease the virus load in HIV-infected patients and, by extension, that the infectious cell entry step is a valid target for antiviral chemotherapy of HIV disease. The SCID-hu Thy/Liv model in effect provides a rapid means of assessing the potential of compounds with novel modes of antiviral action, as well as the potential of antiviral drug combinations.

Animals↗
PubMed1996

Use of standardized SCID-hu Thy/Liv mouse model for preclinical efficacy testing of anti-human immunodeficiency virus type 1 compounds.

We have developed standardized procedures and practices for infection of SCID-hu Thy/Liv mice with human immunodeficiency virus type 1 for the prophylactic administration of antiviral compounds and for evaluation of the antiviral effect in vivo. Endpoint analyses included quantitation of viral load by intracellular p24 enzyme-linked immunosorbent assay, DNA PCR for the presence of proviral genomes, flow cytometry to measure the representation of CD4+ and CD8+ cells, and cocultivation for the isolation of virus. Efficacy tests in this model are demonstrated with the nucleoside analogs zidovudine and dideoxyinosine and with the nonnucleoside reverse transcriptase inhibitor nevirapine. This small-animal model should be particularly useful in the preclinical prioritization of lead compounds within a common chemical class, in the evaluation of alternative in vivo dosing regimens, and in the determination of appropriate combination therapy in vivo.

Animals↗
PubMed1995

Embryo brain kinase: a novel gene of the eph/elk receptor tyrosine kinase family.

A new gene belonging to the Eph/Eck/Elk receptor tyrosine kinase family has been cloned from mouse brain. The gene maps to mouse chromosome 4. In the adult brain it is expressed exclusively and abundantly in the hippocampus. We propose to name it Ebk (embryo brain kinase), as in situ hybridisation shows expression in many parts of the developing mouse brain. The most abundant expression is in the subcommissural organ, and the earliest expression is in the forebrain neural folds, in rhombomeres 2-6, and in somites and heart. Other regions positive at various stages include the cochlear duct, trigeminal ganglion, lung, first branchial arch, and tooth primordia. Also positive are areas of mesenchyme underlying various epithelia during morphogenesis, especially in the mouth and nose, as well as in the eyelids and toes. We compare these patterns with the available data on the 12 other known members of this gene family. Most of them, like Ebk, are expressed in brain (especially adult hippocampus and embryonic rhombomeres) and in organs rich in epithelia (especially lung), although the spatial and temporal patterns differ. We suggest that combinatorial patterns of these receptors act as labels for the regional identity of neurons and epithelia, and could mediate fine control of neurite pathfinding and epithelial morphogenesis.

Aging↗
PubMed1995

Combined ultrasound and fluorescence spectroscopy for physico-chemical imaging of atherosclerosis.

This paper describes a combined ultrasonic and spectroscopic system for remotely obtaining physico-chemical images of normal arterial tissue and atherosclerotic plaque. Despite variations in detector-tissue separation, R, fluorescence powers corresponding to pixels in the image are converted to the same set of calibrated units using distance estimations from A-mode ultrasound reflection times. An empirical model, validated by Monte Carlo simulations of light propagation in tissue, is used to describe changes in fluorescence power as a function of R. Fluorescence spectra of normal and atherosclerotic human aorta obtained with this system are presented as a function of R. To compensate for changes in fluorescence power with R, the empirical model was used in each case to calculate the fluorescence power at a constant reference value of R(Rref = 1.67 mm). Prior to compensation, tissue fluorescence power decreased more than a factor of two as R was increased from 2.5 to 5 mm. Following compensation, the fluorescence power varied less than +/- 10% of the average compensated peak. The chemical composition of each sample was determined by fitting its fluorescence spectrum (in calibrated units) to a model of tissue fluorescence incorporating structural protein and ceroid fluorescence, as well as structural protein and hemoglobin attenuation. Parameters of the fit were used to classify tissue type. Without compensation for distance variation, classification of tissue type was frequently incorrect; however, with compensation, predictive value was high. A 1-D chemical image of a section of human aorta containing both normal and atherosclerotic regions obtained with this system is also presented. After compensation for detector-sample separation, tissue classifications along the cross-section closely resemble those obtained from histology. Regions of elevated ceroid concentration and intimal thickening are clearly observable in the resultant chemical image. The potential value of this type of system in the diagnosis and treatment of coronary artery disease is discussed.

Aorta↗
PubMed1994

In vivo diagnosis of cervical intraepithelial neoplasia using 337-nm-excited laser-induced fluorescence.

Laser-induced fluorescence at 337-nm excitation was used in vivo to differentiate neoplastic [cervical intraepithelial neoplasia (CIN)], nonneoplastic abnormal (inflammation and human papilloma viral infection), and normal cervical tissues. A colposcope (low-magnification microscope used to view the cervix with reflected light) was used to identify 66 normal and 49 abnormal (5 inflammation, 21 human papilloma virus infection, and 23 CIN) sites on the cervix in 28 patients. These sites were then interrogated spectroscopically. A two-stage algorithm was developed to diagnose CIN. The first stage differentiated histologically abnormal tissues from colposcopically normal tissues with a sensitivity, specificity, and positive predictive value of 92%, 90%, and 88%, respectively. The second stage differentiated preneoplastic and neoplastic tissues from nonneoplastic abnormal tissues with a sensitivity, specificity, and positive predictive value of 87%, 73%, and 74%, respectively. Spectroscopic differences were consistent with a decrease in the absolute contribution of collagen fluorescence, an increase in the absolute contribution of oxyhemoglobin attenuation, and an increase in the relative contribution of reduced nicotinamide dinucleotide phosphate [NAD(P)H] fluorescence as tissue progresses from normal to abnormal in the same patient. These results suggest that in vivo fluorescence spectroscopy of the cervix can be used to diagnose CIN at colposcopy.

Cervix Uteri↗
PubMed1993

Emergence of vancomycin-resistant enterococci in New York City.

Enterococci, a common cause of nosocomial infection, are intrinsically resistant to most antimicrobials and readily acquire additional resistance. Vancomycin-resistant enterococci (VRE) have caused clusters of nosocomial infections since 1988. In April, 1991, the New York City Department of Health asked all city laboratories to submit suspected VRE isolates for confirmation. Clinical and epidemiological characteristics of the first 100 patients with VRE were identified, and antimicrobial susceptibility testing, restriction enzyme analysis, and DNA-DNA hybridisation with the vanA gene probe were done. From September, 1989, to October, 1991, 361 patients with VRE were identified at 38 hospitals. The number of hospitals reporting VRE increased from 1 in 1989 to 38 by October, 1991. 98% of 100 VRE infections were nosocomially acquired and 83% patients had received vancomycin and/or a cephalosporin in the 30 days before isolation of VRE. Of 23 isolates from 21 of the first 100 patients, 19 (83%) were resistant to all available antimicrobials. Four vanA probing patterns were noted, and restriction enzyme analysis of the 23 isolates revealed 14 strains. VRE have emerged rapidly in New York City. Molecular analyses suggest that a highly mobile genetic element--eg, a transposon--is responsible for the rapid spread of vancomycin resistance.

Aged↗
PubMed1993

A population-based study of multiple sclerosis in twins: update.

This study is a 7.5-year follow-up of a population-based series of twins with multiple sclerosis (MS) whose mean age now exceeds 50 years. The twin pairs were identified through the Canadian nationwide system of MS clinics and were drawn from a population of 5,463 patients. After 7.5 years, the monozygotic concordance rate increased from 25.9 to 30.8% and the dizygotic-like sex concordance rate from 2.4 to 4.7%. These results are very similar to those of other population-based studies and to our own modified replication twin data reported here. We interpret the data to mean that MS susceptibility is genetically influenced, and a single dominant or even a single recessive gene is unlikely to account for this effect. The difference in concordance rates suggests that at least two or more genes are operative. These data also have important implications for the nature of the environmental effect(s) in MS susceptibility. Most monozygotic twins are discordant even after a correction for age and magnetic resonance imaging findings. This unambiguously demonstrates the powerful effect of nonheritable factors.

Adult↗
PubMed1993

N-acetyl-L-cysteine protects endothelial cells but not L929 tumor cells from tumor necrosis factor-alpha-mediated cytotoxicity.

The effect of N-acetyl-L-cysteine on the cytotoxicity of tumor necrosis factor-alpha was investigated in cultured bovine pulmonary artery endothelial cells and L929 mouse tumor cells. In endothelial cells, a 72-h incubation with tumor necrosis factor-alpha (100 ng/ml) reduced the number of viable cells to 27% of control. Simultaneous incubation with N-acetyl-L-cysteine (0.5-5 mmol/l) protected endothelial cells from tumor necrosis factor-alpha-mediated cytotoxicity and increased viability in a concentration-dependent fashion to 69% of control. Under the same conditions, a 72-h incubation with tumor necrosis factor-alpha (100 ng/ml) reduced the number of viable L929 tumor cells to 31% of control. However, this cytotoxic response remained unaltered in the presence of N-acetyl-L-cysteine (0.5-5 mmol/l). Similar results were obtained when using a lower concentration of tumor necrosis factor-alpha (50 ng/ml). These findings demonstrate protection from tumor necrosis factor-alpha-mediated toxicity by N-acetyl-L-cysteine in endothelial cells but not in a tumor cell line. It is concluded that N-acetyl-L-cysteine might serve as a therapeutic agent to limit the vascular toxicity of tumor necrosis factor-alpha without affecting its antineoplastic activity.

Acetylcysteine↗