Biomedical subjects

M Bell

Publications and source records attributed to M Bell.

At least 37 records · Page 2Linked to original sources

PubMed2001

Quantitative determination of 3,3'-diindolylmethane in urine of individuals receiving indole-3-carbinol.

Indole-3-carbinol (I3C) or, more correctly, its acid condensation products act as chemoprotective agents via several mechanisms. It induces the expression of cytochrome P-450 1A1, which shifts the estrogen metabolic pathway in favor of C-2 hydroxylation and away from the formation of 16 alpha-hydroxyestrone, a suspected endogenous carcinogen. Increased 16 alpha-hydroxylation of estrogen is associated with greater risk of cancer of the cervix, breast, endometrium, and larynx. The production of 4-hydroxyestrone is also inhibited by I3C. I3C can induce a G1 cell cycle arrest in human MCF-7 breast cancer cells. It can suppress aberrant crypt foci. I3C significantly inhibits the cell adhesion, spreading, and invasion associated with an upregulation of PTEN (a tumor suppressor gene) and E-cadherin (a regulator of cell-cell adhesion) expression in T47-D human breast cancer cells. Thus I3C exhibits anticancer activities by suppressing breast tumor cell growth and metastatic spread. A gas chromatography-mass spectrometry method for the quantitation of diindolylmethane, the principal acid condensation product of I3C, has been developed for use in determining compliance in subjects who have been treated with I3C. The method utilizes a 1-ml urine sample. We have used this method to correlate I3C ingestion with regression of cervical intraepithelial neoplasia in a population of women at risk for cervical cancer. The assay provides an objective marker of consumption using a noninvasive biological fluid and illustrates that diindolylmethane may be used as a marker of compliance in I3C dietary intervention studies.

Anticarcinogenic Agents↗

PubMed2001

Screening for abuse: barriers and opportunities.

Domestic abuse is the leading cause of injuries and death among women of childbearing age in the United States. The broad purpose of this research is to discover how pregnant women's psychological and behavioral responses to abuse affect birth outcomes. To select a diverse sample of women, we identified 8 prenatal care sites and completed the human subjects approval process with each. Rates of screening for abuse range from all but 12 women over a 2-1/2-year period at one site to no screening for abuse at another site. In this article, we will review pertinent literature and discuss the supports and barriers we observed when implementing an abuse screening program using the Abuse Assessment Screen, a well-tested and valid clinical instrument. Suggestions will be made for improving the screening rates at those sites where screening is absent or inconsistent.

Attitude of Health Personnel↗

PubMed2001

Promoting responsiveness between mothers with depressive symptoms and their infants.

PURPOSE: To test the efficacy of an interactive coaching intervention to promote responsiveness between mothers experiencing postpartum depressive symptoms (PPDS) and their infants. DESIGN: An experimental design with 117 postpartum women in the Northeastern United States. METHODS: Participants were randomly assigned either to the treatment or control group. Both groups had home visits at 4-8 weeks, 10-14 weeks, and 14-18 weeks postpartum and mother-infant interaction was videotaped and coded for responsiveness. The treatment group also received a coached behavioral intervention designed to promote maternal-infant responsiveness. Measures included the Edinburgh Postnatal Depression Scale, the Beck Depression Inventory-II, and the Dyadic Mutuality Code. FINDINGS: The hypothesis, that the treatment group would show significantly higher maternal-infant responsiveness after the intervention, was supported. No effect of the intervention on depression scores was found. A significant increase in responsiveness and a significant decrease in depression scores occurred over time for both treatment and control groups. No interaction between group and time was detected. CONCLUSIONS: The study showed that a coaching strategy had a positive effect on maternal-infant interaction in this sample. Future research is needed to test coaching interventions in conjunction with other strategies targeted to promote maternal-infant responsiveness and to reduce PPDS.

Adolescent↗

PubMed2001

Protocol for detection of biofilms on needleless connectors attached to central venous catheters.

Central venous catheter needleless connectors (NCs) have been shown to develop microbial contamination. A protocol was developed for the collection, processing, and examination of NCs to detect and measure biofilms on these devices. Sixty-three percent of 24 NCs collected from a bone marrow transplant center contained biofilms comprised primarily of coagulase-negative staphylococci.

Biofilms↗

PubMed2001

Utility of paired BACTEC MYCO/F LYTIC blood culture vials for detection of bacteremia, mycobacteremia, and fungemia.

In previous bloodstream infection studies in Malawi, we inoculated blood from a single venesection into a single BACTEC MYCO/F LYTIC (MFL) vial. Inoculation of one vial, however, would be expected to reduce the sensitivity of bloodstream pathogen detection with MFL vials. To ascertain the degree of this loss of sensitivity, blood was drawn from each of 228 febrile, adult inpatients in Malawi and 5 ml of each blood sample was inoculated into each of two MFL vials. Of 228 paired vials, 51 (22%) were both positive, 172 (75%) were both negative, and 5 (3%) had discordant results. Bloodstream infection would have been detected in 11 (92%) of 12 patients with mycobacteremia and 38 (92%) of 41 patients with bacteremia had only one MFL vial been inoculated. Our study shows that a second MFL vial does not significantly increase diagnostic sensitivity.

Bacteremia↗

PubMed2001

Recognition, assessment and treatment of depression in geriatric nursing home residents.

Depression is the most common, treatable psychiatric disorder found in elderly nursing home residents. Approximately 1.5 million people older than the age of 65 currently reside in nursing homes, and this number is projected to increase substantially with the aging of the U.S. population. Estimates for major depression range from 12% to 22% and 16% to 30% for minor depression, yet the majority of cases remain either unrecognized or untreated. Untreated depression is associated with increased morbidity, mortality, functional impairment, and decreased quality of life for residents. Risk factors for depression include physical illness and disability, polypharmacy, nursing home placement, and environmental factors. The clinical features of depression are often uncharacteristic of the mood changes noted in younger individuals, including somatic symptoms, eating disorders, anxiety, aggression, and cognitive and functional impairment. The on-site nurse practitioner in the nursing home has a pivotal role as a member of the interdisciplinary care team in assessing and managing depression collaboratively with the nursing home staff. Treatment modalities include antidepressant therapy, psychiatric evaluation, psychotherapy, and electroconvulsive therapy. Improving the nursing home environment maybe a key factor in preventing and treating depression in elders.

Age of Onset↗

PubMed2001

The effect of neighborhood-based community organizing: results from the Seattle Minority Youth Health Project.

OBJECTIVE: To evaluate the effect of a community mobilization and youth development strategy to prevent drug abuse, violence, and risky sexual activity. DATA SOURCES/STUDY SETTING: Primary surveys of youth, parents, and key neighborhood leaders were carried out at baseline (1994) and at the end of the intervention period (1997). The study took place in four intervention and six control neighborhoods in Seattle. STUDY DESIGN: The study was designed as a randomized controlled trial with neighborhood as the unit of randomization. The intervention consisted of a paid community organizer in each neighborhood who recruited a group of residents to serve as a community action board. Key variables included perceptions of neighborhood mobilization by youth, parents, and key neighborhood leaders. DATA COLLECTION/EXTRACTION METHODS: Youth surveys were self-administered during school hours. Parent and neighborhood leader surveys were conducted over the phone by trained interviewers. PRINCIPAL FINDINGS: Survey results showed that mobilization increased to the same degree in both intervention and control neighborhoods with no evidence of an overall intervention effect. There did appear to be a relative increase in mobilization in the neighborhood with the highest level of intervention activity. CONCLUSION: This randomized study failed to demonstrate a measurable effect for a community mobilization intervention. It is uncertain whether the negative finding was because of a lack of strength of the interventions or problems detecting intervention effects using individual-level closed-end surveys.

Adolescent↗

PubMed2000

Sequence and analysis of chromosome 5 of the plant Arabidopsis thaliana.

The genome of the model plant Arabidopsis thaliana has been sequenced by an international collaboration, The Arabidopsis Genome Initiative. Here we report the complete sequence of chromosome 5. This chromosome is 26 megabases long; it is the second largest Arabidopsis chromosome and represents 21% of the sequenced regions of the genome. The sequence of chromosomes 2 and 4 have been reported previously and that of chromosomes 1 and 3, together with an analysis of the complete genome sequence, are reported in this issue. Analysis of the sequence of chromosome 5 yields further insights into centromere structure and the sequence determinants of heterochromatin condensation. The 5,874 genes encoded on chromosome 5 reveal several new functions in plants, and the patterns of gene organization provide insights into the mechanisms and extent of genome evolution in plants.

Animals↗

PubMed2000

Inotropic stimulation induces cardiac dysfunction in transgenic mice expressing a troponin T (I79N) mutation linked to familial hypertrophic cardiomyopathy.

The cardiac troponin T (TnT) I79N mutation has been linked to familial hypertrophic cardiomyopathy and a high incidence of sudden death, despite causing little or no cardiac hypertrophy. In skinned fibers, I79N increased myofilamental calcium sensitivity (Miller, T., Szczesna, D., Housmans, P. R., Zhao, J., deFreitas, F., Gomes, A. V., Culbreath, L., McCue, J., Wang, Y., Xu, Y., Kerrick, W. G., and Potter, J. D. (2001) J. Biol. Chem. 276, 3743-3755). To further study the functional consequences of this mutation, we compared the cardiac performance of transgenic mice expressing either human TnT-I79N or human wild-type TnT. In isolated hearts, cardiac function was different depending on the Ca(2+) concentration of the perfusate; systolic function was significantly increased in Tg-I79N hearts at 0.5 and 1 mmol/liter. At higher Ca(2+) concentrations, systolic function was not different, but diastolic dysfunction became manifest as increased end-diastolic pressure and time to 90% relaxation. In vivo measurements by echocardiography and Doppler confirmed that base-line systolic function was significantly higher in Tg-I79N mice without evidence for diastolic dysfunction. Inotropic stimulation with isoproterenol resulted only in a modest contractile response but caused significant mortality in Tg-I79N mice. Doppler studies ruled out aortic outflow obstruction and were consistent with increased chamber stiffness. We conclude that in vivo, the increased myofilament Ca(2+) sensitivity due to the I79N mutation enhances base-line contractility but leads to cardiac dysfunction during inotropic stimulation.

Animals↗

PubMed2000

Acute changes of myocardial creatine kinase gene expression under beta-adrenergic stimulation.

Creatine kinase (CK) plays a crucial role in myocardial energy metabolism. Alterations in CK gene expression are found in hypertrophied and failing heart, but the mechanisms behind these changes are unclear. This study tests the hypothesis that increased adrenergic stimulation, which is observed in heart failure, induces changes of myocardial CK-activity, -isoenzyme distribution and -gene expression that are characteristic of the failing and hypertrophied heart. Isolated rat hearts were perfused (constant pressure of 80 mmHg) with red cell suspensions. Following a 20-min warm-up period, perfusion for 3 h with 10(-8) M (iso 3 h) or without (control 3 h) isoproterenol was started or experiments were immediately terminated (control 0 h). Left ventricular tissue was analyzed for total CK-activity, CK-isoenzyme distribution and, by use of quantitative RT-PCR, for B-CK, M-CK, mito-CK and GAPDH- (as internal standard) mRNA. After beta-adrenergic stimulation (iso 3 h) but not after control perfusion (control 3 h) a roughly threefold increase in B-CK mRNA levels and a decrease in M-CK mRNA levels by 18% was found. There were no significant differences among the three groups in total CK-activity and in distribution of CK-MM, CK-BB, CK-MB and mito-CK. Thus, beta-adrenergic stimulation induces a switch in CK gene expression from M-CK to B-CK, which is characteristic for the hypertrophied and failing heart. This may be interpreted as an adaptive mechanism making energy transduction via CK more efficient at times of increased metabolic demand.

Adrenergic beta-Agonists↗

PubMed2000

NEAR at eros: imaging and spectral results

Eros is a very elongated (34 kilometers by 11 kilometers by 11 kilometers) asteroid, most of the surface of which is saturated with craters smaller than 1 kilometer in diameter. The largest crater is 5.5 kilometers across, but there is a 10-kilometer saddle-like depression with attributes of a large degraded crater. Surface lineations, both grooves and ridges, are prominent on Eros; some probably exploit planes of weakness produced by collisions on Eros and/or its parent body. Ejecta blocks (30 to 100 meters across) are abundant but not uniformly distributed over the surface. Albedo variations are restricted to the inner walls of certain craters and may be related to downslope movement of regolith. On scales of 200 meters to 1 kilometer, Eros is more bland in terms of color variations than Gaspra or Ida. Spectra (800 to 2500 nanometers) are consistent with an ordinary chondrite composition for which the measured mean density of 2.67 +/- 0.1 grams per cubic centimeter implies internal porosities ranging from about 10 to 30 percent.

Journal Article↗

PubMed2000

Natural T, gammadelta, and NK cells in mycobacterial, Salmonella, and human immunodeficiency virus infections.

NK cells, gammadelta T cell antigen receptor chain-positive cells, and CD3(+)CD16/56(+) (natural T [NT]) cells are involved in innate immunity and immunoregulation; however, their role in clinical infection is not well defined. Cytofluorometric analysis was used to examine peripheral blood from bacteremic, nonbacteremic, and healthy human immunodeficiency virus (HIV)-positive and -negative persons in Malawi, Africa. Mycobacteremia was associated with a higher proportion of CD3(+)CD8(-) gammadelta cells (median, 16.6% vs. 0.7% for all other cells; P<.001), and Salmonella bacteremia was associated with a higher proportion of NT cells (4.3% vs. 2.2%; P=. 002). HIV plasma RNA levels were weakly positively correlated with NT cells (rs=.39; P=.002), NK cells (rs=.38; P=.003), and gammadelta cells (rs=.43; P<.001). Compared with patients who survived, patients who died had a higher percentage of NT cells (3.7% vs. 1. 9%; P=.017) and a higher percentage of NT cells that spontaneously produced interferon-gamma (2.4% vs. 1.2%; P=.035). The data support the clinical relevance of gammadelta and NT cells in mycobacterial, Salmonella, and HIV infections and of NT cells in mortality.

Adolescent↗

PubMed2000

U4 small nuclear RNA genes of trypanosomes: cloning of the Leptomonas seymouri gene and mutational analysis of core snRNP assembly.

Trans mRNA splicing in trypanosomatids requires as cofactors small nuclear RNAs (snRNAs) U2, U4, U5, and U6, in addition to the spliced leader (SL) RNA. To allow a phylogenetic comparison and functional analysis of trypanosomatid U4 snRNAs, we have cloned the single-copy gene for the Leptomonas seymouri U4 snRNA. In addition, a putative U4 snRNA gene from Leishmania tarentolae was identified by database searching. Using an episomal expression system, we introduced mutations into the conserved Sm region of the L. seymouri U4, which is the putative binding site for the common proteins that are present in each of the trans-spliceosomal snRNPs. As demonstrated by CsCl density gradient centrifugation, Sm mutant U4 snRNAs are non-functional in core RNP assembly. Furthermore, we present evidence by cell fractionation that U4 snRNAs with Sm mutations are partially defective in nuclear-cytoplasmic translocation. Taken together this indicates that the Sm site of U4 snRNA is responsible for stable core RNP assembly and nuclear localization.

Animals↗

PubMed2000

Human topoisomerase IIalpha and IIbeta interact with the C-terminal region of p53.

The p53 tumor suppressor protein is a critical regulator of cell cycle progression and apoptosis following exposure of cells to DNA damaging agents such as ionizing radiation or anticancer drugs. An important group of anticancer drugs, including compounds such as etoposide and doxorubicin (Adriamycin), interacts with DNA topoisomerase II (topo II), causing the accumulation of enzyme-DNA adducts that ultimately lead to double-strand breaks and cell death via apoptosis. Human topo IIbeta has previously been shown to interact with p53, and we have extended this analysis to show that both topo IIalpha and IIbeta interact with p53 in vivo and in vitro. Furthermore, we show that the regulatory C-terminal basic region of p53 (residues 364-393) is necessary and sufficient for interaction with DNA topo II.

Alternative Splicing↗

PubMed2000

Sensitivity to myc-induced apoptosis is retained in spontaneous and transplanted lymphomas of CD2-mycER mice.

To study the effects of the Myc oncoprotein in a regulatable in vivo system, we generated lines of transgenic mice in which a tamoxifen inducible Myc fusion protein (c-mycER) is expressed under the control of the CD2 locus control region. Activation of the Myc oncoprotein resulted in both proliferation and apoptosis in vivo. Lines with a high transgene copy number developed spontaneous lymphomas at low frequency, but the tumour incidence was significantly increased with tamoxifen treatment. Surprisingly, we found that cellular sensitivity to Myc-induced apoptosis was retained in tumours from these mice and in most lymphoma cell lines, even when null for p53. Resistance to Myc-induced apoptosis could be conferred on these cells by co-expression of Bcl-2. However, acquired resistance is clearly not an obligatory progression event as sensitivity to apoptosis was retained in transplanted tumours in athymic mice. In conclusion, lymphomas arising in CD2-mycER mice retain the capacity to undergo apoptosis in response to Myc activation and show no phenotypic evidence of the presence of an active dominant inhibitor.

Animals↗

PubMed2000

Soluble glycoprotein 130 (gp130) attenuates OSM- and LIF-induced cartilage proteoglycan catabolism.

Oncostatin M (OSM) and leukaemia inhibitory factor (LIF) exhibit pleiotropic biological activities and share many structural and genetic features. The two cytokines bind with high affinity to the same receptor (LIF/OSM receptor), which consists of the LIF receptor alpha chain (LIFRalpha) and the signal transduction unit gp130. A soluble form of the beta chain of the receptor complex called soluble gp130 (sgp130) has been cloned. In this study, we sought to determine whether recombinant sgp130 or anti-gp130 Ab could attenuate the resorption of proteoglycans induced by OSM and LIF in articular cartilage explants. The results show that at high concentrations sgp130 is capable of attenuating both LIF and OSM mediated resorption. In contrast, anti-gp130 Ab selectively inhibited the stimulation of proteoglycan (PG) release by OSM, albeit minimally. The failure of anti-gp130 to attenuate LIF stimulated PG resorption may be due to the normal interaction of LIF with LIFRalpha and unfettered heterodimerization of LIFRalpha with gp130 in the presence of the antibody. The results indicate that sgp130 and anti-gp130 can modulate cartilage PG metabolism in vitro. Whether sgp130 may have therapeutic activity in models of arthritis or indeed in arthritic diseases remains to be determined.

Animals↗

PubMed2000

Home literacy activities and their influence on early literacy skills.

The relationship between the home environments of 66 children and their language and literacy development was examined. After accounting for child age, parent education, and child ability as indexed by scores on a rapid automatized naming task and Block Design of the WPPSI-R, shared book reading at home made no contribution to the prediction of the literacy skills of letter name and letter sound knowledge in kindergarten. In contrast, home activities involving letters predicted modest and statistically significant amounts of variance. For the areas of receptive vocabulary and phonological sensitivity, neither shared book reading nor letter activities were predictive. Follow-up to mid-Grade 2 underscored the importance of letter name/sound knowledge and phonological sensitivity in kindergarten in accounting for individual differences in later achievement in reading comprehension, phonological spelling, and conventional spelling.

Age Factors↗

PubMed2000

Fas-independent apoptosis in T-cell tumours induced by the CD2-myc transgene.

Depending on the cellular context, the Myc oncoprotein is capable of promoting cell proliferation or death by apoptosis. These observations suggest that apoptosis in response to deregulated gene expression may represent a natural brake to tumour development. The pathways by which Myc induces apoptosis are as yet poorly characterised although recent observations on rat fibroblasts over-expressing Myc have demonstrated a requirement for the Fas pathway. To investigate the role of Fas in Myc-induced lymphomagenesis we backcrossed CD2-myc mice onto an lpr background. Rates of tumour development and phenotypic properties, including levels of apoptosis were indistinguishable from CD2-myc controls. Further, tumour cell lines derived from mice expressing a regulatable form of Myc showed inducible apoptosis at similar rates regardless of their lpr genotype. These results show that activation of c-myc and loss of Fas do not collaborate in T lymphoma development and that Myc-induced apoptosis in T-cells occurs by Fas-independent pathways.

Animals↗