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Biomedical subjects

M Brown

Publications and source records attributed to M Brown.

At least 109 records · Page 6Linked to original sources

Geographical distribution of breast cancers on the mammogram: an interval cancer database.

Auditing interval cancers is an important part of a breast screening radiologist's continuing education. We set out to determine whether the position of interval cancers on the mammogram differs from those detected at screening. The 773 interval cancers so far identified, and the first 200 screen detected cancers, have been entered onto a Microsoft Access 97 database developed to record pathological and radiological features, including the position of the cancer on a stylized diagram using a "point and click" system. Reports were generated showing positions of all interval cancers by classification and reader. The distribution of true interval cancers is statistically different from screen detected cancers on both views. The distribution of the false negative and screen detected cancers only differs on the oblique view. False negative and true interval cancers are of the same distribution on both craniocaudal and oblique views. However, these differences do not appear to be practically useful when applied to individual readers. We have developed a database that allows systematic recording of pathological and radiological information regarding breast cancers. Additionally, it can record the geographic position of the cancer with minimal memory requirements. Statistical differences in the distribution of false negative and screen detected cancers have been demonstrated and the stylized diagrams reinforce the importance of the conventional review areas. Although this has not identified any "blind spots" in our own readers, it nevertheless provides film readers with a tool to audit their own work.

Breast Neoplasms↗

The association of school environments with youth physical activity.

OBJECTIVES: This study assessed the association of school environmental characteristics with student physical activity on campus. METHODS: Physical activity areas (n = 137) at 24 public middle schools were assessed for area type, size, and improvements (e.g., basketball courts). Student physical activity and the presence of equipment and supervision were directly observed before school, after lunch, and after school. RESULTS: Environmental characteristics explained 42% of the variance in the proportion of girls who were physically active and 59% of the variance for boys. CONCLUSIONS: School environments with high levels of supervision and improvements stimulated girls and boys to be more physically active.

Adolescent↗

On a variant of Stroop's paradigm: which cognitions press your buttons?

The Stroop effect typically refers to the fact that the time to identify the color of a visually presented word is affected by the relationship between the word and the color When the (irrelevant) word is semantically related to the color (e.g., the word green, presented in red) response time is slower than if the word is neutral or unrelated. One question that has been posed concerns whether semantics plays a role only when the task requires an explicit verbal response, or whether it also plays a role when the response is manual. Sharma and McKenna (1998) have reported that semantics plays a role only when the response is vocal. A reanalysis of their data shows that semantics also plays a role when manual responses are made.

Cognition↗

Impact of acid-related disorders in the United States.

Acid-related disorders are common conditions that negatively impact quality of life for a significant number of people nationwide. The pathology of these conditions involves an imbalance between acid secretion by gastric parietal cells and the ability of upper GI tract mucosa to defend against the effects of the acid. Therefore, therapy is targeted at elevating gastric pH. PPIs are used to control the effects of excessive acid secretion. This class of drugs has a unique mechanism of action that inhibits the final pathway to gastric acid secretion--the parietal cell proton pump.

Antacids↗

Cofactor dynamics and sufficiency in estrogen receptor-regulated transcription.

Many cofactors bind the hormone-activated estrogen receptor (ER), yet the specific regulators of endogenous ER-mediated gene transcription are unknown. Using chromatin immunoprecipitation (ChIP), we find that ER and a number of coactivators rapidly associate with estrogen responsive promoters following estrogen treatment in a cyclic fashion that is not predicted by current models of hormone activation. Cycles of ER complex assembly are followed by transcription. In contrast, the anti-estrogen tamoxifen (TAM) recruits corepressors but not coactivators. Using a genetic approach, we show that recruitment of the p160 class of coactivators is sufficient for gene activation and for the growth stimulatory actions of estrogen in breast cancer supporting a model in which ER cofactors play unique roles in estrogen signaling.

Breast Neoplasms↗

Chemical dependency treatment and employment outcomes: results from the 'ADATSA' program in Washington State.

The Alcohol and Drug Addiction Treatment and Support Act (ADATSA) created a treatment program for indigent clients in Washington State. This research assesses the relationship between the level of treatment services received and subsequent employment outcomes. Clients who completed their plan of treatment earned more than those who did not, controlling for other factors. Those clients who received vocational services, in addition to completing treatment, earned more than those who completed treatment only. While on average wages were low, this study does show that clients once deemed 'unemployable' can become productive.

Adult↗

Microbiological risk assessment: a new approach to food safety control.

The food industry is continually looking to be innovative in the development and production of food. New techniques are also being employed to distribute the food, and even the way the consumer treats the food before consumption has changed dramatically over recent years, for example, with the development of microwavable meals. These changes can lead to differences in the pathogens encountered and the general level of immunity in the population. This in turn puts increased emphasis on food producers to know and understand more about the pathogens likely to occur in the products they are making and their origin. To help food manufacturers tackle this consistently, Microbiological Risk Assessment (MRA) is being applied as a systematic tool to allow effective decisions to be made to reduce the impact of pathogens on health.

Animals↗

The structural basis of repertoire shift in an immune response to phosphocholine.

The immune response to phosphocholine (PC)-protein is characterized by a shift in antibody repertoire as the response progresses. This change in expressed gene combinations is accompanied by a shift in fine specificity toward the carrier, resulting in high affinity to PC-protein. The somatically mutated memory hybridoma, M3C65, possesses high affinity for PC-protein and the phenyl-hapten analogue, p-nitrophenyl phosphocholine (NPPC). Affinity measurements using related PC-phenyl analogues, including peptides of varying lengths, demonstrate that carrier determinants contribute to binding affinity and that somatic mutations alter this recognition. The crystal structure of an M3C65-NPPC complex at 2.35-A resolution allows evaluation of the three light chain mutations that confer high-affinity binding to NPPC. Only one of the mutations involves a contact residue, whereas the other two have indirect effects on the shape of the combining site. Comparison of the M3C65 structure to that of T15, an antibody dominating the primary response, provides clear structural evidence for the role of carrier determinants in promoting repertoire shift. These two antibodies express unrelated variable region heavy and light chain genes and represent a classic example of the effect of repertoire shift on maturation of the immune response.

Amino Acid Sequence↗

Polymorphic repeat in AIB1 does not alter breast cancer risk.

STATEMENT OF FINDINGS: We assessed the association between a glutamine repeat polymorphism in AIB1 and breast cancer risk in a case-control study (464 cases, 624 controls) nested within the Nurses' Health Study cohort. We observed no association between AIB1 genotype and breast cancer incidence, or specific tumor characteristics. These findings suggest that AIB1 repeat genotype does not influence postmenopausal breast cancer risk among Caucasian women in the general population.

Adult↗

Stat4 is expressed in activated peripheral blood monocytes, dendritic cells, and macrophages at sites of Th1-mediated inflammation.

Stat4 is a key transcription factor involved in promoting cell-mediated immunity, whose expression in mature cells has been reported to be restricted to T and NK cells. We demonstrate here, however, that Stat4 expression is not restricted to lymphoid cells. In their basal state, monocytes do not express Stat4. Upon activation, however, IFN-gamma- and LPS-treated monocytes and dendritic cells express high levels of Stat4. Monocyte-expressed Stat4 in humans is phosphorylated in response to IFN-alpha, but not IL-12. In contrast, the Th2 cytokines, IL-4 and IL-10, specifically down-regulate Stat4 expression in activated monocytes, while having little effect on Stat6 expression. Moreover, macrophages in synovial tissue obtained from patients with rheumatoid arthritis express Stat4 in vivo, suggesting a potential role in a prototypical Th1-mediated human disease. IFN-alpha-induced Stat4 activation in human monocytes represents a previously unrecognized signaling pathway at sites of Th1 inflammation.

Arthritis, Rheumatoid↗

Increased gene expression of brown fat uncoupling protein (UCP)1 and skeletal muscle UCP2 and UCP3 in MAC16-induced cancer cachexia.

Weight loss in cancer cachexia is attributable to decreased food intake and/or enhanced energy expenditure. We investigated the roles of the uncoupling proteins (UCPs) UCPI, -2, and -3 in a murine model of cachexia, the MAC16 adenocarcinoma. Weight fell to 24% below that of non-tumor-bearing controls (P < 0.01) 18 days after MAC16 inoculation, with significant reductions in fat-pad mass (-67%; P < 0.01) and muscle mass (-20%; P < 0.01). Food intake was 26-60% lower (P < 0.01) than in controls on days 17-18. Non-tumor-bearing mice, pair-fed to match MAC16-induced hypophagia, showed less weight loss (10% below controls, P < 0.01; 16% above MAC-16, P < 0.01) and smaller decreases in fat-pad mass (21% below controls, P < 0.01). Core temperature in MAC16 mice was significantly lower (-2.4 degrees C, P < 0.01) than in controls, and pair-feeding had no effect. MAC16 mice showed significantly higher UCP1 mRNA levels in brown adipose tissue (BAT) than in controls (+63%, P < 0.01), and pair-feeding had no effect. UCP2 and -3 expression in BAT did not differ significantly between groups. By contrast, UCP2 mRNA levels in skeletal muscle were comparably increased in both MAC16 and pair-fed groups (respectively, 183 and 163% above controls; both, P < 0.05), with no significant difference between these two groups. Similarly, UCP3 mRNA was significantly higher than controls in both MAC16 (+163%, P < 0.05) and pair-fed (+253%, P < 0.01) groups, with no significant difference between the two experimental groups. Overexpression of UCP1 in BAT in MAC16-bearing mice may be an adaptive response to hypothermia, which is apparently induced by tumor products; increased thermogenesis in BAT could increase total energy expenditure and, thus, contribute to tissue wasting. Increased UCP2 and -3 expression in muscle are both attributable to reduced food intake and may be involved in lipid utilization during lipolysis in MAC16-induced cachexia.

Adenocarcinoma↗

Specific association of estrogen receptor beta with the cell cycle spindle assembly checkpoint protein, MAD2.

Estrogen receptors (ERs) are ligand-activated transcription factors that regulate gene expression and cell growth. Two ERs now have been identified: ERalpha and the more recently discovered ERbeta. The physiological function of ERbeta remains unclear, but evidence from vascular injury studies and from ERbeta knockout mice suggests that ERbeta may be involved in the regulation of cellular proliferation. Here we show a direct and specific interaction between ERbeta and the cell cycle mitotic spindle assembly checkpoint protein, MAD2 (mitosis arrest-deficient 2). The ERbeta-MAD2 interaction was identified by screening of a yeast two-hybrid system vascular endothelial cell library with ERbeta and confirmed with glutathione S-transferase-fusion protein interaction studies. In contrast, ERalpha did not interact with MAD2 in either the two-hybrid system or in the protein-protein interaction experiments. Amino acids 173-208 in the hinge region of ERbeta were sufficient to mediate the interaction with MAD2 in the two-hybrid system and in glutathione S-transferase-fusion protein studies. These data identify a link between ERbeta and MAD2 of potential importance to regulation of the cell cycle and support a function of ERbeta distinct from the established role of ERs as transcription factors.

Amino Acid Sequence↗

Changes in GABA-immunoreactivity during development of the rostral subdivision of the nucleus of the solitary tract.

GABA plays an important role in the processing of gustatory information in the rostral nucleus of the solitary tract. The following study used post-embedment immunohistochemistry in the rat brainstem to localize GABA at both the light and electron microscopic levels to characterize the developmental distribution of GABA and synaptogenesis of GABA-immunoreactive terminals in the rostral nucleus of the solitary tract. During the first postnatal week, GABA is present in the rostral nucleus of the solitary tract, but less of it is synaptic than any time later in development. Of the few synaptic terminals present at postnatal day 1, less than 20% are GABA-immunoreactive. This proportion more than doubles to reach adult levels by postnatal day 10. By weaning (postnatal day 20), GABA-immunoreactive cells are found in nearly the same density as in the adult. Development continues after weaning and is characterized by a disproportionate loss of non-GABA-containing cells. Finally, one previously identified subtype of GABA-immunoreactive terminal matures very late during the postweaning phase of development. The study provides the first analysis of the development of GABA-related circuitry in the rostral nucleus of the solitary tract using anatomical methods. These data provide the background with which to view the emerging physiology of developing taste neurons.

Animals↗

A clinical evaluation of a locking orthodontic facebow.

Standard orthodontic facebows may accidentally detach from the appliance buccal tubes at night; this could reduce the effectiveness of extra oral traction and occasionally cause an injury. To try and prevent facebow detachment at night a facebow with a locking mechanism was introduced. This study assessed the ability of 706 consecutively treated patients to learn to wear and use this facebow. The facebows were fitted in 9 different practices supervised by 12 orthodontists. Data from the patients and orthodontists were collected over a 2-year period and covered approximately 166,550 nights. All the orthodontists were able to fit and adjust the facebow; a total of 697 patients successfully used the facebow. Accidental detachment of the facebow at night was reported to be less than 1%. This indicates a significant improvement in the safety of the facebow and should help to improve compliance by increasing the number of hours of wear achieved by the patients.

Accident Prevention↗

Gram positive infection in trauma patients: new strategies to decrease emerging Gram-positive resistance and vancomycin toxicity.

Bacterial resistance to antibiotics has become a serious problem in medicine. Particularly worrisome is the increasing incidence of multi-resistant organisms such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). Not surprisingly, in view of the high incidence of life-threatening infections and heavy antibiotic use, resistance has become very frequent and problematic in intensive care units. The standard approach for the treatment of MRSA is vancomycin or teicoplanin. Long-term therapeutic and unrestricted prophylactic use of vancomycin has given rise to VRE which in turn may lead to the emergence of vancomycin-resistant S. aureus (VRSA) through plasmid mediated transmission. In order to reduce the incidence of VRE and to avoid the emergence of VRSA, vancomycin use should be restricted and alternative antibiotic strategies should be developed. Using those antibiotics to which MRSA are still generally sensitive, perhaps in combination with new ones, such as, quinupristin/dalfopristin, should be entertained. We performed a retrospective review of the Gram-positive infections in our Level 1 Trauma Center Intensive Care Unit, and an analysis of the resistance patterns of the NMSA infections showed that additional resistance rarely develops within less than 5 days. We then designed a new strategy for the treatment of MRSA infections. This strategy consists of the sequential use of a range of antibiotics with activity against MRSA in short 5-7 day pulses until the full clinical course is completed. Studies validating the benefit of this approach are currently in preparation.

Anti-Bacterial Agents↗