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Biomedical subjects

K Williams

Publications and source records attributed to K Williams.

At least 55 records · Page 3Linked to original sources
PubMed2002

Neuroinflammation of the nigrostriatal pathway during progressive 6-OHDA dopamine degeneration in rats monitored by immunohistochemistry and PET imaging.

We investigated the microglial response to progressive dopamine neuron degeneration using in vivo positron emission tomography (PET) imaging and postmortem analyses in a Parkinson's disease (PD) rat model induced by unilateral (right side) intrastriatal administration of 6-hydroxydopamine (6-OHDA). Degeneration of the dopamine system was monitored by PET imaging of presynaptic dopamine transporters using a specific ligand (11)C-CFT (2beta-carbomethoxy-3beta-(4-fluorophenyl) tropane). Binding of (11)C-CFT was markedly reduced in the striatum indicating dopaminergic degeneration. Parallel PET studies of (11)C-PK11195 (1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3 isoquinoline carboxamide) (specific ligand for activated microglia) showed increased binding in the striatum and substantia nigra indicative of a microglial response. Postmortem immunohistochemical analyses were performed with antibodies against CR3 for microglia/macrophage activation. Using a qualitative postmortem index for microglial activation we found an initially focal, then widespread microglial response at striatal and nigral levels at 4 weeks postlesion. These data support the hypothesis that inflammation is a significant component of progressive dopaminergic degeneration that can be monitored by PET imaging.

Animals↗
PubMed2002

Validity and reliability of an interviewer-administered questionnaire to measure the severity of lower urinary tract symptoms of storage abnormality: the Leicester Urinary Symptom Questionnaire.

OBJECTIVE: To develop a valid and reliable interviewer-administered questionnaire to measure the presence and severity of storage abnormality symptoms of incontinence, urgency, frequency and nocturia. SUBJECTS AND METHODS: Subjects were 930 men and women aged >/=40 years, taking part in a randomized controlled trial of a continence nurse practitioner (CNP) service. Criterion validity was tested by comparing questionnaire responses to 24-h pad test and 3-day urinary diary. Responsiveness was assessed by comparing questionnaire responses before and after treatment. Questions about urgency were investigated for construct validity in patients taking part in the trial who underwent urodynamic investigation (243). Test-retest and inter-rater reliability was measured at approximately 6 days in subjects recruited to an associated epidemiological study (104 and 102, respectively). RESULTS: The questionnaire responses showed significant associations with pad-test and diary measures. Questions about the severity of daytime incontinence performed better than those measuring night-time incontinence. The response categories of soaked, wet, damp and almost dry had better associations with the pad test than other measures of the severity of incontinence. Test-retest and inter-rater reliability was good for all questions, and all were responsive to change in symptoms, showing significant differences before and after treatment. CONCLUSION: There is a clear need for standardization of measurement using well-validated instruments. This interviewer-administered questionnaire is valid, reliable and sensitive to change in a wide range of severity of symptoms, and in both men and women aged >/=40 years. The questionnaire provides a useful assessment tool for primary and secondary care in research and clinical settings.

Aged↗
PubMed2002

A case of levetiracetam (Keppra) poisoning with clinical and toxicokinetic data.

BACKGROUND: Levetiracetam (Keppra) is a new anticonvulsant used to treat partial complex seizures that is also being investigated for its mood-stabilizing properties. Although its precise mechanism of action is unknown, levetiracetam does not appear to directly interact with the GABA system. We report the first intentional overdose with levetiracetam including clinical effects and serial serum concentrations. CASE REPORT: A 38-year-old woman reportedly ingested 60 (500 mg) tablets of levetiracetam that she used as a mood-stabilizing medication for bipolar disorder. She had no other prescription medications available and no other medical history. She vomited 4 hours after ingestion and presented to the ED 2 hours later. In the ED, the patient was obtunded and was intubated secondary to respiratory depression. Her only other significant clinical finding was diminished deep tendon reflexes. Serum ethanol, lithium, carbamazepine, phenytoin, and valproic acid levels were all negative as was a subsequent urine screen for drugs of abuse. Her levetiracetam serum concentration was 400 microg/mL at 6 hours, 72 microg/mL at 18 hours, and 60 microg/mL at 20.5 hours (therapeutic serum concentration is 10-37 microg/mL). The elimination half-life was calculated to be 5.14 hours. She was extubated the next hospital day and recovered without sequelae. CONCLUSION: In overdose, levetiracetam is sedating and causes respiratory depression, however, recovery is rapid with supportive care. This is the first reported case of levetiracetam overdose; serial serum concentrations suggest first-order elimination even at concentrations 10-40 fold higher than therapeutic.

Adult↗
PubMed2002

Family and parenting interventions for conduct disorder and delinquency: a meta-analysis of randomised controlled trials.

AIMS: To determine whether family and parenting interventions benefit children and adolescents with conduct disorder and delinquency. METHODS: Meta-analysis of eight randomised controlled trials involving 749 children and adolescents (aged 10-17 years) with conduct disorder and/or delinquency. Criminality, academic performance, future employment, problem behaviour, family functioning, parental mental health, and peer relations were evaluated. RESULTS: Family and parenting interventions significantly reduced the time spent by juvenile delinquents in institutions (weighted mean difference 51.34 days). There was also a significant reduction in the risk of a juvenile delinquent being rearrested (relative risk 0.66) and in their rate of subsequent arrests at 1-3 years (standardised mean difference -0.56). CONCLUSIONS: The evidence suggests that family and parenting interventions for juvenile delinquents and their families have beneficial effects on reducing time spent in institutions and their criminal activity. In addition to the obvious benefit to the participant and their family, this may result in a cost saving for society.

Adolescent↗
PubMed2002

Prevalence of faecal incontinence in adults aged 40 years or more living in the community.

BACKGROUND: Prevalence studies of faecal incontinence in the general population are rare and the impact of faecal incontinence on quality of life has not been previously addressed. AIMS: To establish the prevalence of faecal incontinence in adults in terms of frequency of leakage, degree of soiling, and level of impact on quality of life. METHODS: In a cross sectional postal survey, 15 904 adults aged 40 years or more (excluding residents of nursing and residential homes) were selected randomly by household from the Leicestershire Health Authority patient register. Participants were asked to complete a confidential health questionnaire. Major faecal incontinence was defined as soiling of underwear or worse with a frequency of several times a month or more. Respondents were also asked if bowel symptoms had an impact on their quality of life. RESULTS: From a total sample of 10 116 respondents, 1.4% reported major faecal incontinence and 0.7% major faecal incontinence with bowel symptoms that had an impact on quality of life. Major faecal incontinence was significantly associated with a lot of impact on quality of life (odds ratio 12.4, 95% confidence interval 7.5-20.6). Incontinence was more prevalent and more severe in older people but there was no significant difference between men and women. CONCLUSIONS: This study has confirmed that faecal incontinence is a fairly common symptom, particularly in older people. Faecal incontinence in men has received little attention in the past and the results from this study indicate that it is as much of a problem in men as it is in women while the level of unmet need in this group is high. Estimates of need for health care for this symptom should be multidimensional and assess both the severity of symptoms and the impact it has on quality of life.

Adult↗
PubMed2002

Temporal changes in maternal serum biochemical markers of trisomy 21 across the first and second trimester of pregnancy.

BACKGROUND: Many maternal serum markers show concentration changes in Down's syndrome pregnancies but the magnitude of the change in median marker levels varies with gestation. To date these changes have not been accurately specified. METHODS: The trends in marker median levels between 6 and 20 weeks of gestation were examined for alphafetoprotein (AFP), free beta human chorionic gonadotrophin (Fbeta-hCG), total human chorionic gonadotrophin (ThCG) and pregnancy-associated plasma protein A (PAPP-A) by a meta-analysis of data obtained from our collaborative studies and routine screening programmes for Down's syndrome over a 10-year period. Data were available from between 709 and 1082 Down's syndrome pregnancies and from between 14607 and 153909 unaffected pregnancies for each marker. The median multiple of the median (MoM) and mean log10MoM for each marker at each completed week of gestation were estimated and the trend with gestation smoothed using a weighted least squares regression model. RESULTS: The gestational ages at which maximum separation of marker levels occurred, comparing affected and unaffected pregnancies, and the respective regressed median MoMs and mean log10MoMs, were: for AFP at 16 weeks, 0.72 MoM, -0.14288log10MoM; for Fbeta-hCG at 15 weeks, 2-24MoM, 0.35034 log10MoM; for ThCG at 16 weeks, 1.93 MoM, 0.28548 log10MoM, as well as before 8 weeks (<0.65 MoM, -0.18853 log10MoM); and for PAPP-A before 8 weeks, <0.33 MoM, -0.47727 log10MoM. CONCLUSION: There is significant temporal variation in mean log10MoM values for the screening markers investigated. Screening algorithms, modified to take account of this variation, should allow more accurate gestation-specific risks to be calculated in individual pregnancies.

Biomarkers↗
PubMed2002

Development and validation of a new monoclonal antibody to mammalian aromatase.

The biosynthesis of oestrogens from androgens is catalysed by the aromatase complex, an essential component of which is the aromatase cytochrome P450 (P450 arom) protein. Expression of a functional P450 arom is essential for normal fertility in males and females and the sequence of the protein is highly conserved. We have raised a new monoclonal antibody against a conserved peptide and validated it on fixed tissue sections of the rat, common marmoset (Callthrix jacchus) and human. The monoclonal antibody was used successfully for Western analysis and specifically reacted with a 55 kDa protein in microsomal extracts. On sections of ovaries in all three species, expression in follicles was specific to the mural granulosa cells of antral follicles and was present in corpora lutea. In the human and marmoset, staining of luteal cells was markedly heterogeneous and did not appear to vary consistently with the stage of the cycle. The intensity of immunostaining was elevated in corpora lutea from pregnant rats and following human chorionic gonadotropin rescue in the human. In the testis, the highest levels of expression were observed in the Leydig cells within the interstitium. In adult rat and marmoset, and possibly also in the human, some P450 arom was associated with the cytoplasm surrounding elongate spermatids but other germ cells were immunonegative. In conclusion, a new monoclonal antibody specific for P450 arom recognises the protein in rodent, primate and human. Its ability to work on fixed tissue sections will facilitate identification of individual cells expressing P450 arom within complex tissues.

Animals↗
PubMed2002

Culture and co-culture of DU145 prostate carcinoma, osteoblasts and HT-29 colon carcinoma cells on a fabricated type III collagen matrix.

DU145 prostate carcinoma cells cultured on type III collagen possessed a highly migratory potential which was twice as much as HT-29 colon carcinoma cells. Prior to attachment to collagen, DU145 cells were highly reactive for fibronectin and after attachment clear zones between cells and collagen suggested protease activity. HT-29 cells attached to type III collagen forming dome-like polyps, however, tight and/or gap junctions were not observed. hFob osteoblasts were co-cultured with DU145 to establish a prostate cancer-collagen matrix barrier-bone cell metastasis model. Osteoblasts maintained their differentiated osteoblastic characteristics on one side of the collagen barrier, demonstrating high alkaline phosphatase, osteocalcin and insulin growth factor (IGF) activities. hFob cell growth was prominent adjacent to demineralized bone matrix particles (BMPs) embedded in type III collagen. The collagen matrix was deteriorated on the DU145 side of the collagen barrier. The DU145-collagen III-hFob model will allow an evaluation of the influence of the matrix on prostate cancer-bone cell interaction and regulation by growth factors.

Alkaline Phosphatase↗
PubMed2001

Concordance between the CC chemokine receptor 5 genetic determinants that alter risks of transmission and disease progression in children exposed perinatally to human immunodeficiency virus.

If CC chemokine receptor 5 (CCR5)-dependent mechanisms at the time of initial virus exposure are important determinants of virus entry and disease outcome, then the polymorphisms in CCR5 that influence risk of transmission and disease progression should be similar; this hypothesis was tested in a cohort of 649 Argentinean children exposed perinatally to human immunodeficiency virus type 1 (HIV-1). Two lines of evidence support this hypothesis. First, CCR5 haplotype pairs associated with enhanced risk of transmission were the chief predictors of a faster disease course. Second, some of the haplotype pairs associated with altered rates of transmission and disease progression in children were similar to those that we previously found influenced outcome in European American adults. This concordance suggests that CCR5 haplotypes may serve as genetic rheostats that influence events occurring shortly after initial virus exposure, dictating not only virus entry but, by extension, also the extent of early viral replication.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Characteristics and work experiences of hospitalists in the United States.

BACKGROUND: Little is known about the personal characteristics, work-related attitudes, or professional experiences of hospitalists. In considering the future of hospital medicine as a viable career choice for physicians (primarily, internists), these issues should be examined in a systematic fashion. Learning more about hospitalists and their work can enhance dialogue about the advantages and shortcomings of such a career from the perspective of the individual physician. METHODS: A self-administered mail survey was sent to 820 hospitalists who are dues-paying members of the National Association of Inpatient Physicians and who spend 50% or more of their time doing clinical work, teaching, or research related to hospital medicine. Attitudes about topics such as job-related burnout and job satisfaction were tapped, as well as information about different professional and social experiences. The analyses were performed using descriptive statistics and analysis of variance techniques. RESULTS: Analysis was based on 393 responses (48% response rate). Results show hospitalists to be a group of younger, mostly male, early-career individuals with high levels of job satisfaction and autonomy, low levels of burnout, and a long-term commitment to remaining in the role. Hospital medicine is a source of positive social and professional work experiences related to interactions with physician peers, patients and their families, and nonphysician hospital coworkers. Key components of hospitalists' jobs, practices, and workload are coalescing. However, certain developments, such as changing patterns of compensation and the enlisting of more general internists and women as hospitalists, merit further examination. CONCLUSIONS: The results offer insight into the physicians who are becoming hospitalists, the jobs and settings in which they work, and how hospitalists experience their everyday work lives. Valuable baseline data are provided for assessment of attitudes, such as burnout, that should be examined regularly in this fledgling group. This study complements research looking at the performance-related outcomes of hospitalists, and it can be used by various stakeholders to better understand and assess the long-term potential of what is being proposed as a new career path.

Adult↗
PubMed2001

Protein sizing on a microchip.

We have developed a microfabricated analytical device on a glass chip that performs a protein sizing assay, by integrating the required separation, staining, virtual destaining, and detection steps. To obtain a universal noncovalent fluorescent labeling method, we have combined on-chip dye staining with a novel electrophoretic dilution step. Denatured protein-sodium dodecyl sulfate (SDS) complexes are loaded on a chip and bind a fluorescent dye as the separation begins. At the end of the separation channel, an intersection is used to dilute the SDS below its critical micelle concentration before the detection point. This strongly reduces the background due to dye molecules bound to SDS micelles and also increases the peak amplitude by 1 order of magnitude. Both the on-chip staining and SDS dilution steps occur in the 100-ms time scale and are approximately 10(4) times faster than their conventional counterparts in SDS-PAGE. This represents a much greater speed increase due to microfabrication than has been obtained in other assay steps such as electrophoretic separations. We have designed and tested a microchip capable of sequentially analyzing 11 different samples, with sizing accuracy better than 5% and high sensitivity (30 nM for carbonic anhydrase).

Carbonic Anhydrases↗
PubMed2001

Organ-specific regulation of the CD8 T cell response to Listeria monocytogenes infection.

The intestinal mucosal CD8 T cell response to infection with Listeria monocytogenes was measured using MHC class I tetramers and was compared with the response in peripheral blood, secondary lymphoid tissue, and liver. To assess the vaccination potential of Listeria and to analyze responses in C57BL/6 mouse strains, a recombinant Listeria expressing OVA (rLM-ova) was generated. The response peaked at 9 days postinfection with a much larger fraction of the intestinal mucosa and liver CD8 T cell pool OVA specific, as compared with the spleen. However, these differences were not linked to bacterial titers in each site. The higher responses in lamina propria and liver resulted in a larger CD8 memory population in these tissues. Furthermore, the level of memory induced was dependent on infectious dose and inversely correlated with the magnitude of the recall response after oral challenge. Recall responses in the tissues were most robust in the lamina propria and liver, and reactivated Ag-specific T cells produced IFN-gamma. Infection of CD40- or MHC class II-deficient mice induced poor CD8 T cell responses in the intestinal mucosa, but only partially reduced responses in the spleen and liver. Overall, the results point to novel pathways of tissue-specific regulation of primary and memory antimicrobial CD8 T cell responses.

Administration, Oral↗
PubMed2001

Family and parenting interventions in children and adolescents with conduct disorder and delinquency aged 10-17.

BACKGROUND: Conduct disorder and delinquency are significant problems for children and adolescents and their families, with the potential to consume much of the resources of the health, social care and juvenile justice systems. A number of family and parenting interventions have been recommended and are used for these conditions. The aim of this review was to determine if these interventions are effective in the management of conduct disorder and delinquency in children and adolescents, aged 10-17. OBJECTIVES: To determine if family and parenting interventions improve the child/adolescent's behaviour; parenting and parental mental health; family functioning and relations; and have an effect on the long term psychosocial outcomes for the child/adolescent. SEARCH STRATEGY: Randomised controlled trials were identified through searching the Cochrane Controlled Trial Register (CCTR), databases (MEDLINE, EMBASE, PsycINFO, CINAHL, Sociofile, ERIC, Healthstar), reference lists of articles and contact with authors. SELECTION CRITERIA: Randomised controlled trials with a major focus on parenting and/or family functioning were eligible for inclusion in the review. Trials needed to include at least one objective outcome measure (e.g. arrest rates) or have used a measure that had been published in peer review publications and validated for the relevant purpose. Studies were required to have a control group, which could be a no intervention group, a wait list group or a usual intervention group (e.g. probation). Trials in children and adolescents aged 10 to 17 years with conduct disorder and/or delinquency and their families were considered. Conduct disorder was defined by a standardised psychological assessment (for example, using a child behaviour checklist), or a psychiatric diagnosis. Delinquency was defined by a referral from a juvenile justice or another legal system for a child/adolescent who has committed a serious crime e.g assault and/or offended on at least two occasions. DATA COLLECTION AND ANALYSIS: Two reviewers independently reviewed all eligible studies for inclusion, assessed study quality (allocation concealment, blinding, follow up, clinically important outcomes) and extracted data. Heterogeneity was assessed using the Chi squared test of heterogeneity along with visual inspection of the data. A significance level less than 0.1 was interpreted as evidence of statistically significant heterogeneity. For data where heterogeneity was found the reviewers looked for an explanation. If studies with heterogeneous results were thought to be comparable the statistical synthesis of the results was done using a random effects model. This model takes into account within-study sampling error and between-studies variation in the assessment of uncertainty and will give wider confidence intervals to the effect size and hence a more conservative result. Sensitivity analysis was performed to explore the effects of the varying quality of the studies included on the results. MAIN RESULTS: Of the nine hundred and seventy titles initially identified through the search strategy, eight trials met the inclusion criteria. A total of 749 children and their families were randomised to receive a family and parenting intervention or to be in a control group. In seven of these studies the participants were juvenile delinquents and their families and in only one the participants were children/adolescents with conduct disorder who had not yet had contact with the juvenile justice system. At follow up, family and parenting interventions significantly reduced the time spent by juvenile delinquents in institutions (WMD 51.34 days, 95%CI 72.52 to 30.16). There was also a significant reduction in the risk of a juvenile delinquent being re arrested (RR 0.66, 95%CI 0.44 to 0.98) and in their rate of subsequent arrests at 1-3 years (SMD -0.56, 95% CI -1.100 to - 0.03). For both of these outcomes there was substantial heterogeneity in the results suggesting a need for caution in interpretation. At present there is insufficient evidence that family and parenting interventions reduce the risk of being incarcerated (RR=0.50, 95% CI 0.20 to 1.21). No significant difference was found for psychosocial outcomes such as family functioning, and child/adolescent behaviour. REVIEWER'S CONCLUSIONS: The evidence suggests that family and parenting interventions for juvenile delinquents and their families have beneficial effects on reducing time spent in institutions. This has an obvious benefit to the participant and their family and may result in a cost saving for society. These interventions may also reduce rates of subsequent arrest but at present these results need to be interpreted with caution due to the heterogeneity of the results.

Adolescent↗
PubMed2001

High incidence of cardiovascular events in a rheumatoid arthritis cohort not explained by traditional cardiac risk factors.

OBJECTIVE: To compare the incidence of cardiovascular (CV) events in persons with rheumatoid arthritis (RA) with that in people from the general population, adjusting for traditional CV risk factors. METHODS: Two hundred thirty-six consecutive patients with RA were assessed for the 1-year occurrence of 1) CV-related hospitalizations, including myocardial infarction, stroke or other arterial occlusive events, or arterial revascularization procedures, or 2) CV deaths. Both outcomes were ascertained by medical records or death certificates. For comparison, we used CV events that occurred during an 8-year period among participants in an epidemiologic study of atherosclerosis and CV disease who were ages 25-65 years at study entry. We calculated the age- and sex-stratified incidence rate ratio (IRR) of CV events between the 2 cohorts and used Poisson regression to adjust for age, sex, smoking status, diabetes mellitus, hypercholesterolemia, systolic blood pressure, and body mass index. RESULTS: Of the 236 RA patients, 234 were observed for 252 patient-years, during which 15 CV events occurred. Of these, 7 incident events occurred during the 204 patient-years contributed by patients ages 25-65 years, for an incidence of 3.43 per 100 patient-years. In the comparison cohort, 4,635 community-dwelling persons were followed up for 33,881 person-years, during which 200 new events occurred, for an incidence of 0.59 per 100 person-years. The age- and sex-adjusted IRR of incident CV events associated with RA was 3.96 (95% confidence interval [95% CI] 1.86-8.43). After adjusting for CV risk factors using Poisson regression, the IRR decreased slightly, to 3.17 (95% CI 1.33-6.36). CONCLUSION: The increased incidence of CV events in RA patients is independent of traditional CV risk factors. This suggests that additional mechanisms are responsible for CV disease in RA. Physicians who provide care to individuals with RA should be aware of their increased risk of CV events and implement appropriate diagnostic and therapeutic measures.

Adult↗
PubMed2001

Central nervous system perivascular cells are immunoregulatory cells that connect the CNS with the peripheral immune system.

Perivascular cells are a heterogeneous population found in the central nervous system (CNS) and the peripheral nervous system (PNS). Several terms are used for these cells, including perivascular cells, perivascular macrophages, perivascular microglia, fluorescent granular perithelial cells (FGP), or Mato cells. Different terminology used may reflect subpopulations of perivascular cells within different anatomic regions and experimental paradigms, neuropathological conditions, and species studied. Different terminology also points to the lack of clear consensus of what cells are perivascular cells in different disease states and models, especially with breakdown of the blood-brain barrier (BBB). Despite this, there is consensus that perivascular cells, although a minor component of the CNS, are important immunoregulatory cells. Perivascular cells are bone marrow derived, continuously turn over in the CNS, and are found adjacent to CNS vessels. Thus, they are potential sensors of CNS and peripheral immune system perturbations; are activated in models of CNS inflammation, autoimmune disease, neuronal injury and death; and are implicated as phagocytic and pinocytotic cells in models of stroke and hypertension. Recent evidence from our laboratory implicate perivascular cells as primary targets of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infection in the CNS of humans and macaques. This article reviews current knowledge of perivascular cells, including anatomic location and nomenclature and putative immunoregulatory roles, and discusses new data on the infection of these cells by SIV, their accumulation after SIV infection, and a possible role of the immune system in SIV encephalitis.

AIDS Dementia Complex↗
PubMed2001

Medium-term open label trial of L-carnitine in Rett syndrome.

Treatment strategies in Rett syndrome so far have been essentially symptomatic and supportive. In order to establish the medium-term effects of L-carnitine, an open label trial was performed in a cohort of 21 Rett syndrome females, with a control group of 62 Rett syndrome females of a similar age, for a 6-month period. Compared with the Rett syndrome controls, treatment with L-carnitine led to significant improvements in sleep efficiency (P=0.027), especially in the subjects with a baseline sleep efficiency less than 90%, energy level (P<0.005) and communication skills (P=0.004). There was no significant difference in the subject's level of physical activity, hand function or in the quality of life of the subject's parents. In addition, before and after comparisons of the treatment group showed improvements in expressive speech (P=0.011). Treatment with L-carnitine seems to be of significant benefit in a subgroup of girls with Rett syndrome. In these girls, small but discernible improvements may be of considerable importance to their parents and carers.

Adolescent↗
PubMed2001

Effects of p,p'-DDE on immature cells in culture at concentrations relevant to the Alaskan environment.

Arctic Alaskan Natives who maintain a traditional lifestyle have a disease profile that is significantly different from the general US population. There is concern that food sources containing environmental pollutants may contribute to this profile. In a preliminary study, umbilical cord blood was examined for the presence of several environmental contaminants. All cord blood samples analyzed thus far contain p,p'-DDE (1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene) with an average concentration of 0.33 microg/l. This study was undertaken to ascertain if this concentration of p,p'-DDE had detectable effects on immature cells in culture. NIH 3T3 (embryonic mouse fibroblast) and WS1 (human fetal fibroblast) cultures were exposed to media containing either 1 or 10 times the average cord blood concentration of p,p'-DDE. Initial experiments indicated that exposure to p,p'-DDE resulted in a decrease in the cell number of both cell types. Subsequent analysis revealed that the decrease in cell number was due to cell death in NIH 3T3 cells and to cell-cycle arrest in WS1 cells. Furthermore, p,p'-DDE decreased the long-term survival of NIH 3T3 but not WS1 cells. This study has demonstrated that p,p'-DDE, at relevant environmental concentrations, has significant effects on two immature mammalian cell types in culture. In addition, these results highlight the necessity for further studies to address the specific effects of p,p'-DDE on developing fetal systems.

3T3 Cells↗