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Biomedical subjects

M A Clark

Publications and source records attributed to M A Clark.

At least 55 records · Page 3Linked to original sources
PubMed2000

Breast and cervical cancer screening: associations with personal, spouse's, and combined smoking status.

The objective of this study was to examine the association of women's cancer screenings with both personal and spouses' smoking status, as well as with the broader context of household smoking, in a United States national-level sample of women aged 42-75 years. Data were from the 1994 National Health Interview Survey Health Promotion Supplement. The sample included 1586 women who reported they were married and living with a spouse in a two-person household. Three measures of smoking status were used: personal smoking status, smoking status of spouse, and household smoking status (self and spouse smoked, spouse only smoked, self only smoked, and both nonsmokers). Using logistic regression modeling, associations were examined between the smoking status measures and three cancer screening indicators: mammogram < or =2 years, clinical breast exam < or =2 years, and Pap test < or =3 years. The both nonsmokers group consistently had the highest screening rates for all three exams. The spouse only smoking group was 10-12% less likely to obtain all three cancer screening tests compared to the both nonsmokers group. The self and spouse group was less likely to report a recent mammogram and clinical breast exam. The self only group did not differ significantly from the both nonsmokers group on any of the cancer screening measures. Results suggest that smoking status of a spouse may be an important correlate of women's cancer screenings.

Adult↗
PubMed1999

Generation of anti-p53 Fab fragments from individuals with colorectal cancer using phage display.

Although many individuals with malignancy develop Abs against p53, little is currently known of the structural features, V gene usage, and degree of somatic mutation of these Abs. Such information is critical to any meaningful understanding of the nature and significance of this humoral immune response to p53. We have constructed phage display libraries from six individuals with colorectal cancer and a demonstrable serum immune response against p53. Following panning with recombinant p53, a total of 43 binding Fab were identified. Four of these Abs bound with high affinity to wild-type denatured p53 (1.19 x 10-8 - 1.57 x 10-8), as determined by BIAcore analysis, and were highly specific for both recombinant and cell line-derived p53, as determined by ELISA and immunoprecipitation. Epitope mapping showed they were reactive with the N terminus of human p53 between residues 27 and 44. Sequence analysis showed that the heavy chains were derived from the VH1 gene family, and the light chains from VL4. The pattern of replacement and silent mutations in the Fab sequence indicated that negative selection had occurred in the framework regions of all the VH genes. We show that lymphocytes from individuals with cancer represent a valuable source of high affinity human Abs against p53. This approach provides an opportunity to examine the genetic structure of these naturally occurring Abs, and to draw inferences regarding the nature of the immune response that produced them. Abs identified in this way have a number of potential therapeutic applications.

Amino Acid Sequence↗
PubMed1999

Smoking and cancer screening for women ages 42-75: associations in the 1990-1994 National Health Interview Surveys.

BACKGROUND: Previous studies have found an association between current smoking and lower rates of mammography and Pap testing. The objective of this study was to investigate the association of smoking status with breast and cervical cancer screening across the 1990-1994 National Health Interview Surveys (NHIS). The NHIS provides a consistent set of independent and dependent variables across several surveys, with data collected by a similar in-person interview methodology from year to year. This report employs more databases than have been used in other analyses that have examined associations between smoking and cancer screening. METHODS: Data were from the health promotion and cancer control supplements to the 1990-1994 NHIS. The target population was women ages 42-75. Associations were examined between smoking status (never, former, <1 pack/day, >/=1 pack/day) and three screening indicators: ever had a mammogram, mammogram in the past 2 years, and Pap test in the past 3 years. Sample sizes ranged from about 3,000 to over 10,800 depending on the respective NHIS survey and dependent variable. Data analyses were conducted by bivariate and multiple logistic regression. RESULTS: Women who smoked >/=1 pack of cigarettes per day were significantly less likely to have had mammography screening in all NHIS surveys, compared to women who never smoked. Adjusted odds ratios were 0.63 to 0.74 for ever had a mammogram, and 0.56 to 0.66 for mammography in the past 2 years. Women who smoked >/=1 pack per day also had lower Pap test rates than women who never smoked in 1992-1994 (adjusted odds ratios of 0.51-0.71). Results for lighter smokers were not as consistent. Former smokers often had significantly higher screening rates than never smokers. CONCLUSIONS: Research still needs to identify reasons for lower screening among women who smoke. Factors to explore include the social networks of smokers and broader health behavior patterns. Clinicians should consider heavier smoking as a marker for risk of not obtaining screening and make assessment of screening status a priority at each visit.

Adult↗
PubMed1999

Providers' smoking cessation attitudes and practices for older patients.

A mail survey of 136 providers in a health maintenance organization in the Chicago metropolitan area examined smoking cessation attitudes and performance of the 4As protocol (asking, advising, assisting, arranging) for patients aged 50 years or older. Asking about smoking was most frequent, followed by arranging, advising, and assisting. Physicians and nurse practitioners performed each of the 4As more often than did registered and licensed practical nurses. In multiple logistic regression analyses, provider type was the only significant predictor of asking about smoking. Advising, assisting, and arranging follow-ups were more likely to be performed by providers who perceived a sense of professional responsibility about older patients' smoking; advising was more likely for providers who perceived that they had enough time to advise older patients about smoking; and assisting and arranging were more likely for providers with a stronger sense of self-efficacy for helping older patients stop smoking.

Aging↗
PubMed1999

Sequence evolution in bacterial endosymbionts having extreme base compositions.

A major limitation on ability to reconstruct bacterial evolution is the lack of dated ancestors that might be used to evaluate and calibrate molecular clocks. Vertically transmitted symbionts that have cospeciated with animal hosts offer a firm basis for calibrating sequence evolution in bacteria, since fossils of the hosts can be used to date divergence events. Sequences for a functionally diverse set of genes have been obtained for bacterial endosymbionts (Buchnera) from two pairs of aphid host species, each pair diverging 50-70 MYA. Using these dates and estimated numbers of Buchnera generations per year, we calculated rates of base substitution for neutral and selected sites of protein-coding genes and overall rates for rRNA genes. Buchnera shows homogeneity among loci with regard to synonymous rate. The Buchnera synonymous rate is about twice that for low-codon-bias genes of Escherichia coli-Salmonella typhimurium on an absolute timescale, and fourfold higher on a generational timescale. Nonsynonymous substitutions show a greater rate disparity in favor of Buchnera, a result consistent with a genomewide decrease in selection efficiency in Buchnera. Ratios of synonymous to nonsynonymous substitutions differ for the two pairs of Buchnera, indicating that selection efficiency varies among lineages. Like numerous other intracellular bacteria, such as Rickettsia and Wolbachia, Buchnera has accumulated amino acids with codons rich in A or T. Phylogenetic reconstruction of amino acid replacements indicates that replacements yielding increased A + T predominated early in the evolution of Buchnera, with the trend slowing or stopping during the last 50 Myr. This suggests that base composition in Buchnera has approached a limit enforced by selective constraint acting on protein function.

AT Rich Sequence↗
PubMed1999

Screening for breast and cervical cancers: the importance of knowledge and perceived cancer survivability.

INTRODUCTION: This study examines the association between recent screening for breast and cervical cancers, knowledge of cancer risk factors, and perceptions of surviving cancer. METHODS: Data were from the Cancer Control Supplement to the 1992 National Health Interview Survey (NHIS-CCS). The dependent variable combined breast and cervical cancer screening practices into a single composite index. Two independent variables combined women's knowledge about breast and cervical cancers into single indicators--one representing risk factor knowledge, the other representing perceived likelihood of surviving breast and cervical cancers following early detection. RESULTS: Multivariate analysis showed that recency of screening for both breast and cervical cancers was associated with knowledge of cancer risk factors and perceptions of surviving cancer. Education, household income, and smoking status also were correlates of comprehensive screening. Significant interactions between income and perceived survivability, and between education and perceived survivability suggested that the effects of income and education on comprehensive screening varied with perceptions about surviving cancer. CONCLUSION: The study suggests that knowledge and attitudinal questions can be combined for two diseases to enhance understanding of who is most likely to be screened comprehensively for breast and cervical cancers. Although national trends show that large percentages of women over age 50 are having mammograms and Pap tests, this progress is not likely to be sustained unless existing barriers are eliminated. Limited knowledge about breast and cervical cancer risk factors and misperceptions about survival from cancer represent two of these barriers.

Aged↗
PubMed1999

The use of fluconazole as a local irrigant for nephrostomy tubes.

OBJECTIVES: Few data exist concerning the combined use of fluconazole systemically and as an irrigant for nephrostomy tubes in a patient with renal candidiasis. The patient described here presented with renal fungal balls obstructing the drainage of urine from her nephrostomy tubes. METHODS: Twelve months after chemoradiation for a stage IIB squamous cell carcinoma of the uterine cervix, a 35-year-old woman presented with renal obstruction necessitating insertion of ureteral stents. After 6 months of chemotherapy, the patient developed uremia. After nephrostomy tubes were placed, renal candidiasis was noted, and fluconazole was begun systemically. When the renal candidiasis failed to clear, nephrostomy tube irrigations were begun. RESULTS: Fourteen days of therapy with fluconazole resulted in the resolution of the uremia. The patient died 6 months later with her nephrostomy tubes in situ and without evidence of candidiasis in her urinary tract. CONCLUSIONS: The patient described was successfully treated without having to remove her nephrostomy tubes. Two other authors have reported the successful use of fluconazole irrigation to treat candidiasis in nephrostomy tubes that was unresponsive to systemic fluconazole. Before the appearance of these reports, the best results were obtained with removal of the catheter in renal candidiasis.

Adult↗
PubMed1998

Sequence analysis of a 34.7-kb DNA segment from the genome of Buchnera aphidicola (endosymbiont of aphids) containing groEL, dnaA, the atp operon, gidA, and rho.

Buchnera aphidicola is a prokaryotic endosymbiont of the aphid Schizaphis graminum. From past and present nucleotide sequence analyses of the B. aphidicola genome, we have assembled a 34. 7-kilobase (kb) DNA segment. This segment contains genes coding for 32 open reading frames (ORFs), which corresponded to 89.9% of the DNA. All of these ORFs could be identified with homologous regions of the Escherichia coli genome. The order of the genes with established functions was groELS-trmE-rnpA-rpmH-dnaA-dnaN-gyrB-atpCDGAH FEB-gidA-fdx-hscA- hscB-nifS-ilvDC-rep-trxA-rho. The order of genes in small DNA fragments was conserved in both B. aphidicola and E. coli. Most of these fragments were in approximately the same region of the E. coli genome. The latter organism, however, contained many additional inserted genes within and between the fragments. The results of the B. aphidicola genome analyses indicate that the endosymbiont has many properties of free-living bacteria.

Algal Proteins↗
PubMed1998

Buchnera aphidicola (Aphid endosymbiont) contains genes encoding enzymes of histidine biosynthesis.

Buchnera aphidicola is an endosymbiont of aphids. One of its functions appears to be the synthesis of essential amino acids for the aphid host. A 12.8-kilobase B. aphidicola DNA fragment has been cloned and sequenced. It contains genes encoding all of the enzymes required for the biosynthesis of the essential amino acid histidine. The order of the genes, hisGDCBHAFI, is the same as that found in Escherichia coli and is consistent with their constituting a single transcription unit. The DNA fragment also contained genes involved in aromatic amino acid biosynthesis (aroC), the oxidative pentose pathway (gnd), and 2'-deoxyribonucleotide metabolism (dcd), as well as a tRNA synthase (metG).

Animals↗
PubMed1998

Ulex europaeus 1 lectin targets microspheres to mouse Peyer's patch M-cells in vivo.

The interaction of latex microspheres with mouse Peyer's patch membranous M-cells was studied in a mouse gut loop model after the microspheres were coated with a variety of agents. Carboxylated microspheres (diameter 0.5 micron) were covalently coated with lectins Ulex europaeus 1, Concanavalin A, Euonymus europaeus and Bandeiraea simplicifolia 1 isolectin-B4, human immunoglobulin A or bovine serum albumin. Of the treatments examined, only Ulex europaeus (UEA1) resulted in significant selective binding of microspheres to M-cells. UEA1-coated microspheres bound to M-cells at a level 100-fold greater than BSA-coated microspheres, but binding to enterocytes was unaffected. Incubation of UEA1-coated microspheres with alpha-L-fucose reduced M-cell binding to a level comparable with BSA-coated microspheres. This indicated that targeting by UEA1 was via a carbohydrate receptor on the M-cell surface. Adherence of UEA1-coated microspheres to M-cells occurred within 10 min of inoculation into mouse gut loops and UEA1-coated microspheres were transported to 10 microns below the apical surface of M-cells within 60 min of inoculation. UEA1-coated microspheres also targeted mouse Peyer's patch M-cells after intragastric administration. These results demonstrated that altering the surface chemistry of carboxylated polystyrene microspheres increased M-cell targeting, suggesting a strategy to enhance delivery of vaccine antigens to the mucosal immune system.

Analysis of Variance↗
PubMed1998

Do groups of women aged 50 to 75 match the national average mammography rate?

CONTEXT: As mammography rates increase, an important question is how closely groups of women match or do not match the national-level, average screening percentage. OBJECTIVE: This study employed a classification-tree methodology to combine individual risk factors from multiple logistic regression, in order to more comprehensively define groups of women less (or more) likely to be screened. DESIGN/SETTING: This report was a secondary data analysis drawing on data from the 1992 National Health Interview Survey, Cancer Control Supplement (NHIS-CCS). PARTICIPANTS: Analyses examined mammography status of women aged 50-75 (n = 1,727). MAIN OUTCOME MEASURE: The dependent variable was having a screening mammogram in the past 2 years. Multiple logistic regression (SUDAAN) was conducted first to select significant correlates of screening. A classification-tree analysis (CHAID subroutine of SPSS) was then used to combine the significant correlates into exclusive and exhaustive subgroups. RESULTS: A total of 13 subgroups were identified, of which only six approximated the overall population screening rate. The lowest screening occurred in small clusters of women, which, when added together, formed a larger percentage of the population who were not screened within the past 2 years. CONCLUSIONS: Efforts to increase mammography may face the challenge of identifying relatively small pockets of women and addressing their individual barriers. Further work should be done to find efficient ways to combine individual risk factors into groups at risk for not being screened.

Aged↗
PubMed1998

Studying M cells and their role in infection.

In addition to sampling antigens, M cells are a common route for pathogen invasion. Recent studies have partly defined the mechanisms by which pathogens interact with and exploit M cells as a gateway into the host. New research tools are facilitating studies on M cell infection, differentiation and function.

Animals↗
PubMed1998

Left hemispheric specialization for learned, skilled, and purposeful action.

Three-dimensional motion analyses were performed on trajectories of repetitive "slicing" gestures by 4 participants with left-hemisphere lesions and limb apraxia, 6 participants with right-hemisphere lesions, and 7 neurologically intact participants. Left hemispheric lesioned participants with apraxia, but not right hemispheric lesioned participants showed impaired coupling of spatial and temporal aspects of wrist trajectories and deficits in interjoint coordination. Both groups of brain-lesioned participants differed from control participants in the 3-D plane of the wrist motion. The deficits of some right hemispheric lesioned participants in controlling the plane of wrist motion may be a consequence of left hemispatial neglect with rightward deviations. In contrast, the deficits of apraxic participants in controlling wrist trajectories and coordinating joint motions seem to reflect a deficit in these participants for the movement plan.

Aged↗
PubMed1998

Psychosocial factors and smoking cessation behaviors among smokers who have and have not ever tried to quit.

Relationships between smoking cessation behaviors and demographic characteristics and attitudes were analyzed among two groups of smokers, those who had and had not ever tried to quit. Telephone interviews were completed with 1501 smokers at baseline and at a 3 month follow-up. Multiple logistic regression analyses were used to identify factors that were associated with planning to quit, attempting to quit and quitting smoking within the two groups of smokers. Different patterns of correlates were found across groups and within the three outcome measures, indicating the potential importance of targeting interventions according to whether or not smokers have made a prior quit attempt. These findings also support the value of using multiple outcome measures in the smoking cessation process.

Adult↗
PubMed1998

Effect of a chimeric antibody to tumor necrosis factor-alpha on cytokine and physiologic responses in patients with severe sepsis--a randomized, clinical trial.

OBJECTIVES: Tumor necrosis factor (TNF)-alpha appears central to the pathogenesis of severe sepsis, but aspects of the cytokine cascade and the link to physiologic responses are poorly defined. We hypothesized that a monoclonal antibody to TNF-alpha given early in the course of severe sepsis would modify the pattern of systemic cytokine release and, as a consequence, resuscitation fluid requirements, net proteolysis, and hypermetabolism would be reduced. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Critical Care Unit and University Department of Surgery in a single tertiary care center. PATIENTS: Fifty-six patients (from 92 eligible patients) with severe sepsis. Twenty-eight patients were randomized to treatment, and were comparable with the placebo group for age, gender, race, Acute Physiology and Chronic Health Evaluation II score, and site and type of infection. INTERVENTIONS: A 300-mg single dose of cA2 (a chimeric neutralizing antibody to TNF-alpha) was given intravenously within 12 hrs of the onset of severe sepsis. Standard surgical and intensive care therapy was otherwise delivered. MEASUREMENTS AND MAIN RESULTS: Plasma concentrations of TNF-alpha, interleukin (IL)-1beta IL-6, IL-8, IL-10, soluble 75-kilodalton TNF-alpha receptor (sTNFR-75), and IL-1beta receptor antagonist (IL-1ra) were measured by sandwich enzyme-linked immunosorbent assay before cA2 infusion, 8 hrs later, and then daily for a minimum of 4 days. Sequential changes in total body protein, body water spaces, and resting energy expenditure over 21 days were measured, as soon as patients achieved hemodynamic stability, by in vivo neutron activation analysis, tritium and bromide dilution, and indirect calorimetry, respectively. Twenty-one patients died, ten having received cA2. Suppression of measurable TNF-alpha was observed at 8 hrs with subsequent rebound by 24 hrs after cA2 treatment. The concentrations of other cytokines were high, were not reduced by intervention, and decreased logarithmically over 5 days. Both groups reached hemodynamic stability at similar times (57.5 +/- 11.8 hrs in controls vs. 58.6 +/- 9.2 hrs in the cA2 group) and following similar volumes of infused fluids (29.1 +/- 3.4 L vs. 28.9 +/- 4.4 L). No differences in net proteolysis, resolution of body water expansion, or alteration in resting energy expenditure were demonstrated. CONCLUSION: A single dose of cA2 did not alter the overall pattern of cytokine activation or the profound derangements in physiologic function that accompany severe sepsis.

Adult↗
PubMed1998

Inoculum composition and Salmonella pathogenicity island 1 regulate M-cell invasion and epithelial destruction by Salmonella typhimurium.

In the mouse model of Salmonella typhimurium infection, the specialized antigen-sampling intestinal M cells are the primary route of Salmonella invasion during the early stages of infection. Under certain experimental conditions, M-cell invasion is accompanied by M-cell destruction and loss of adjacent regions of the follicle-associated epithelium (FAE), although the conditions responsible for expression of the cytotoxic phenotype in a proportion of previous studies have not been defined. In the present study, we have demonstrated that the cytotoxic effect exerted by wild-type S. typhimurium on mouse Peyer's patch FAE is dependent on the inoculum composition. We have also demonstrated that the extent of FAE destruction correlates with the extent of M-cell invasion. Bacteria inoculated in Luria-Bertani (LB) broth induce extensive FAE loss and exhibit efficient M-cell invasion, whereas bacteria inoculated in phosphate-buffered saline fail to induce significant FAE disruption and invade M cells at significantly lower levels. Similarly, inoculation in LB significantly enhances invasion of Madin-Darby canine kidney cells by wild-type S. typhimurium. Mutants defective for expression of invA, a component of Salmonella pathogenicity island 1 which is vital for efficient invasion of cultured cells, fail to induce FAE destruction and, when inoculated in LB, are attenuated for M-cell invasion. Variation in inv gene expression is, therefore, one possible mechanism by which inoculate composition may regulate the virulence of wild-type S. typhimurium. Our findings suggest that the composition of the gut luminal contents may be critical in determining the outcome of naturally acquired Salmonella infections and that both vaccine formulation and dietary status of vaccine recipients may significantly affect the efficacy and safety of live Salmonella oral vaccine delivery systems.

Animals↗
PubMed1998

M-cell surface beta1 integrin expression and invasin-mediated targeting of Yersinia pseudotuberculosis to mouse Peyer's patch M cells.

Quantitative analysis of Yersinia pseudotuberculosis infection of murine gut loops revealed that significantly more wild-type bacteria associated with Peyer's patch M cells than with dome enterocytes or goblet cells. An invasin-deficient mutant was significantly attenuated for M-cell invasion, while beta1 integrin expression was demonstrated in the apical membranes of M cells but not enterocytes. M-cell targeting by Yersinia pseudotuberculosis in vivo may, therefore, be mediated primarily by the interaction of invasin with cell surface beta1 integrins.

Adhesins, Bacterial↗