Search PubMed⌕ Search

Biomedical subjects

R Anderson

Publications and source records attributed to R Anderson.

At least 73 records · Page 4Linked to original sources
PubMed2001

Comparisons of two breast cancer risk estimates in women with a family history of breast cancer.

There is an increasing need for accurate prediction methods of assessing individual risk for breast cancer for both clinical and research purposes. The purpose of this study is to compare the Gail and Claus model risk estimates of breast cancer among women with a family history of breast cancer. This study presents risk estimates from two models of breast cancer risk in 491 women 18 to 74 years of age with a family history of breast cancer who were recruited to risk counseling clinical trials in Seattle, Washington between 1996 and 1997. These trials included women from the general population and additional samples of Ashkenazi Jewish, African-American, and lesbian women. We estimated and compared lifetime (to age 79) and 5-year risk for developing breast cancer using the National Surgical Adjuvant Breast and Bowel Project adaptation of the Gail model and the Claus model. About one-quarter of participants fell into the Gail "high" risk category (> or =1.7% risk of developing breast cancer in the next 5 years). The average lifetime risk was estimated at 13.2% by the Gail model and 11.2% by the Claus model. Estimates from the two models were moderately and positively correlated (r = 0.55) with the Gail model yielding a higher estimate than the Claus model for most participants. If women with a family history of breast cancer are being counseled regarding decisions on genetic testing, tamoxifen use, or other preventive measures, presenting both Claus and Gail estimates may be the best option.

Adolescent↗
PubMed2001

Prospective randomized controlled trial of extended-release oxybutynin chloride and tolterodine tartrate in the treatment of overactive bladder: results of the OBJECT Study.

OBJECTIVE: To compare the efficacy and tolerability of extended-release oxybutynin chloride and tolterodine tartrate at 12 weeks in participants with overactive bladder. SUBJECTS AND METHODS: The OBJECT (Overactive Bladder: Judging Effective Control and Treatment) study was a prospective, randomized, double-blind, parallel-group study conducted between March and October 2000 at 37 US study sites. Participants who had between 7 and 50 episodes of urge incontinence per week and 10 or more voids in 24 hours received extended-release oxybutynin, 10 mg/d, or tolterodine, 2 mg twice daily. The outcome measures were the number of episodes of urge incontinence, total incontinence, and micturition frequency at 12 weeks adjusted for baseline. RESULTS: A total of 315 women and 63 men were randomized and treated, and 332 participants (276 women, 56 men) completed the study. At the end of the study, extended-release oxybutynin was significantly more effective than tolterodine in each of the main outcome measures: weekly urge incontinence (P=.03), total incontinence (P=.02), and micturition frequency episodes (P=.02) adjusted for baseline. Both drugs improved symptoms of overactive bladder significantly from baseline to the end of the study as assessed by the 3 main outcome measures (P<.001). Dry mouth, the most common adverse event, was reported by 28.1% and 33.2% of participants taking extended-release oxybutynin and tolterodine, respectively (P=.32). Rates of central nervous system and other adverse events were low and similar in both groups. CONCLUSIONS: Extended-release oxybutynin was more effective than tolterodine as measured by end-of-study urge incontinence, total incontinence, and micturition frequency episodes. Both groups had similar rates of dry mouth and other adverse events.

Aged↗
PubMed2000

Localized biphasic changes in phosphatidylinositol-4,5-bisphosphate at sites of phagocytosis.

Phagocytosis requires localized and transient remodeling of actin filaments. Phosphoinositide signaling is believed to play an important role in cytoskeletal organization, but it is unclear whether lipids, which can diffuse along the membrane, can mediate the focal actin assembly required for phagocytosis. We used imaging of fluorescent chimeras of pleckstrin homology and C1 domains in live macrophages to monitor the distribution of phosphatidylinositol-4,5-bisphosphate (4,5-PIP(2)) and diacylglycerol, respectively, during phagocytosis. Our results reveal a sequence of exquisitely localized, coordinated steps in phospholipid metabolism: a focal, rapid accumulation of 4,5-PIP(2) accompanied by recruitment of type Ialpha phosphatidylinositol phosphate kinase to the phagosomal cup, followed by disappearance of the phosphoinositide as the phagosome seals. Loss of 4,5-PIP(2) correlated with mobilization of phospholipase Cgamma (PLCgamma) and with the localized formation of diacylglycerol. The presence of 4, 5-PIP(2) and active PLCgamma at the phagosome was shown to be essential for effective particle ingestion. The temporal sequence of phosphoinositide metabolism suggests that accumulation of 4,5-PIP(2) is involved in the initial recruitment of actin to the phagocytic cup, while its degradation contributes to the subsequent cytoskeletal remodeling.

Actins↗
PubMed2000

Apparent involvement of the A(2A) subtype adenosine receptor in the anti-inflammatory interactions of CGS 21680, cyclopentyladenosine, and IB-MECA with human neutrophils.

This study was undertaken to identify the adenosine receptor (AR) subtypes which down-regulate the proinflammatory activities of human neutrophils, as well as the involvement of adenosine 3',5'-cyclic monophosphate (cAMP) and its relationship to cellular handling of Ca(2+) in mediating these effects. Neutrophils were treated with varying concentrations (0.01-1 microM) of AR agonists operative at A(1) (N(6)-cyclopentyladenosine, CPA), A(2A) (2(4-[(2-carboxyethyl)phenyl]ethylamino)-5'-N-ethylcarboxamidoadenosi ne, CGS 21680), and A(3) (N(6)-(3-iodobenzyl-5'-N-methylcarbamoyladenosine, IB-MECA) receptors, after which they were activated with the chemoattractant, N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP, 1 microM). Intracellular cAMP, superoxide, and elastase were assayed using radioimmunoassay, lucigenin-enhanced chemiluminescence (LECL), and colorimetric procedures, respectively, while changes in the concentrations of cytosolic Ca(2+) were monitored by fura-2-based spectrofluorimetry. CGS 21680, at all concentrations tested, inhibited superoxide production in a dose-related manner, while CPA and IB-MECA were effective only at the highest concentrations tested (0.5-1 microM). The release of elastase from activated neutrophils was also inhibited by all three AR agonists, but was more sensitive to CGS 21680 and IB-MECA than was superoxide production. The inhibitory effects of all 3 agonists on superoxide production and elastase release were associated with accelerated clearance of Ca(2+) from the cytosol of activated neutrophils, and were effectively neutralized by pretreatment of the cells with the highly selective A(2A)R antagonist, ZM 241385 (4-(2-[7-amino-2-(2-furyl)[1, 2,4]triazolo[2,3-a][1,3,5]triazin-5yl amino]ethyl)phenol). Increased cAMP was detected in neutrophils treated with CGS 21680 and IB-MECA (1 microM). These data support the involvement of the A(2A)R subtype in the suppression of superoxide production and degranulation by activated human neutrophils, probably by cAMP-mediated alterations in Ca(2+) handling.

Adenosine↗
PubMed2000

AIDS in a new millennium.

As we enter the new millennium the world is still facing the challenge of responding to the AIDS pandemic. A new report from the Joint United Nations Programme on HIV/AIDS presents the latest statistics on prevalence, spread, and impact of the disease. In their Perspective, Schwartländer and his colleagues discuss the newly released statistics and the strategies needed to combat the further spread of HIV/AIDS and to reduce prevalence in the most severely affected countries.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Theiler's murine encephalomyelitis virus induces rapid necrosis and delayed apoptosis in myelinated mouse cerebellar explant cultures.

Infection with the Daniel strain of Theiler's murine encephalomyelitis (TMEV-DA) virus induces persistent demyelinating lesions in mice and serves as a model for multiple sclerosis. During the acute phase of the disease, however, viral infection leads to cell death in vivo. Viral-induced death may result directly from viral infection of neural cells, or indirectly, by activation of the immune system. To examine the direct effects of TMEV infection on neural cells, myelinated explant cultures of the murine cerebellum were infected with 10(5) pfu of TMEV-DA for periods ranging from 1 to 72 h. Our results indicate that TMEV-DA replicates in cultured neural tissue. Initially, viral antigen is localized to a few isolated neural cells. However, within 72 h antigen was observed in multiple foci that included damaged cells and extracellular debris. Viral infection led to a rapid and cyclical induction of necrosis with a time period that was consistent with the lytic phase of the viral life-cycle. Simultaneously, we observed an increase in apoptosis 48 h post-infection. Electron micrographic analysis indicated that viral-infected cultures contained cells with fragmented nuclei and condensed cytoplasm, characteristic of apoptosis. The localization of apoptosis to the cerebellar granule cell layer, identified these cells as presumptive granule neurons. Viral infection, however, did not lead to myelin damage, though damaged axons were visible in TMEV-infected cultures. These results suggest that during the acute phase of infection, TMEV targets neural cells for apoptosis without directly disrupting myelin. Myelin damage may therefore result from the activation of the immune system.

Animals↗
PubMed2000

Medical therapy, symptoms, and the distress the cause: relation to quality of life in patients with angina pectoris and/or hypertension.

BACKGROUND: Adverse events during drug therapy can be assessed through measurement of 2 features: their frequency and their severity. Their severity, in turn, can be measured by assessing the distress that they cause. Our goal was to relate the magnitude of the distress induced by treatment with calcium-channel blocking agents to the change in quality of life assessed through psychosocial instruments in patients treated with calcium-channel blocking agents, either for hypertension or for angina pectoris. METHODS: Four hundred seventy-five patients with angina pectoris were randomized to double-blind treatment with PPR (physiological pattern release) verapamil hydrochloride, amlodipine besylate, amlodipineatenolol combination, or placebo. In addition, 557 hypertensive patients were randomized either to PPR verapamil or nifedipine GITS (gastrointestinal system). Both studies were double-blind. RESULTS: Significant differences in treatment of angina pectoris or hypertension, were not found between the regimens. Overall quality of life also failed to show a significant difference in either group. In both groups, however, remarkable concordance was found between the degree of distress associated with specific symptoms and a change in quality of life. An unchanged, stable symptom distress was associated with a significant improvement in the quality of life of about 0.1 SD. Improvement or erosion of symptom distress represented by 1 step was associated with a 0.1- to 0.2-SD change. The extreme change in symptom distress was associated with a substantially larger change in global quality of life. CONCLUSIONS: The magnitude of symptom distress or relief associated with symptoms in 2 patient populations correlated strongly with a shift in quality of life. The assessment of distress associated with symptoms provides valuable additional information on drug therapy.

Adult↗
PubMed2000

Antibiotic prescribing for dental conditions: general medical practitioners and dentists compared.

OBJECTIVE: To compare the level of prescribing and types of antibiotics prescribed for dental problems by general medical practitioners and dentists. DESIGN: Secondary analysis of standard consultation data and prescription records from four different settings. SETTING: 30 participating general practices in the General Practice Morbidity Database for Wales in 1996. SUBJECTS: 1,185 attendances for tooth-related problems, at 30 participating practices in the General Practice Morbidity Database for Wales in 1996. Standard consultation records from a GDP emergency dental rota, and two weekend emergency dental clinics: one in a health centre, the other in a dental hospital. RESULTS: More than two thirds (68%) of attendances at general medical practices for tooth-related problems resulted in a prescription for antibiotics. In contrast less than a third (28%) of patients seen by a GDP rota, about half (52%) of patients at a weekend emergency clinic in a health centre, and just more than a third (38%) of patients attending the dental hospital clinic received antibiotics. General medical practitioners were also more likely to prescribe broad-spectrum antibiotics than dentists. CONCLUSION: For acute dental problems general medical practitioners are more likely to prescribe antibiotics than dentists. There also appear to be inter-professional differences in the tendency to prescribe broad spectrum antibiotics. Initiatives to rationalise prescribing for dental conditions may need to target doctors as well as dentists.

Anti-Bacterial Agents↗
PubMed2000

Crystal structures of ligand complexes of P450eryF exhibiting homotropic cooperativity.

Several mammalian cytochrome P450 (P450) isoforms demonstrate homotropic cooperativity with a number of substrates, including steroids and polycyclic aromatic hydrocarbons. To identify structural factors contributing to steroid and polycyclic aromatic hydrocarbon binding to P450 enzymes and to determine the location of the allosteric site, we investigated interactions of the macrolide hydroxylase P450eryF from Saccharopolyspora erythraea with androstenedione and 9-aminophenanthrene. Spectroscopic binding assays indicate that P450eryF binds androstenedione with an affinity of 365 microM and a Hill coefficient of 1.31 +/- 0.6 and coordinates with 9-aminophenanthrene with an affinity of 91 microM and a Hill coefficient of 1.38 +/- 0.2. Crystals of complexes of androstenedione and 9-aminophenanthrene with P450eryF were grown and diffracted to 2.1 A and 2.35 A, respectively. Electron density maps indicate that for both complexes two ligand molecules are simultaneously present in the active site. The P450eryF/androstenedione model was refined to an r = 18.9%, and the two androstenedione molecules have similar conformations. The proximal androstenedione is positioned such that the alpha-face of carbon-6 is closest to the heme iron, and the second steroid molecule is positioned 5.5 A distal in the active site. The P450eryF/9-aminophenanthrene model was refined to an r = 19.7% with the proximal 9-aminophenanthrene coordinated with the heme iron through the 9-amino group and the second ligand positioned approximately 6 A distal in the active site. These results establish that homotropic cooperativity in ligand binding can result from binding of two substrate molecules within the active site pocket without major conformational changes in the protein.

Bacterial Proteins↗
PubMed2000

Out-of-hours dental services: a survey of current provision in the United Kingdom.

OBJECTIVE: To describe the variety of arrangements for providing out-of-hours dental care in the UK. DESIGN: A telephone interview survey of health authorities and health boards. SETTING: United Kingdom. SUBJECTS: 104 health authority contacts, usually consultants in dental public health, dental advisers or others in a position to describe the local dental service arrangements. RESULTS: At weekends, 25 authorities have no formal dental care arrangements for unregistered patients, 55 have separate arrangements for registered and unregistered patients, and 44 have 'universal access' arrangements--for anyone in an area, regardless of their registration status. On weekday nights over two-thirds (82/124) of UK health authorities have no formal arrangements for unregistered patients. Where there are separate 'safety-net' services intended for unregistered patients only they are usually (in 48 of 55 authorities) emergency treatment sessions. A fifth of authorities reported planned changes to their local out-of-hours arrangements, including the introduction of telephone triage, and moves to make care available at more times, to more people or from centralised premises. CONCLUSIONS: There is extremely wide geographical variation in the organisation of out-of-hours dental services provided in the United Kingdom. In many parts of the UK there are no formal out-of-hours care arrangements for unregistered patients, even at weekends. This unequal provision will mean inequitable access for many unregistered patients. With increasing demands from a growing unregistered population, and various government initiatives to make primary care services more integrated and accessible, the highly fragmented pattern of provision in many areas may no longer be acceptable.

Catchment Area, Health↗
PubMed2000

The onset of germ cell migration in the mouse embryo.

Mouse primordial germ cells (PGCs) are specified between embryonic day 6.5 (E6.5) and E7.5, when they have been visualized as an alkaline phosphatase-positive (AP+) cell population in the developing allantois. By E8.5, they are embedded in the hind-gut epithelium. Previous experiments have suggested different sites for PGCs' origin, and it is unclear how they reach the gut epithelium. We have used transgenic mice expressing GFP under a truncated Oct4 promoter to visualize living PGCs. We find GFP+/AP+ cells in the posterior end of the primitive streak as a dispersed population of cells actively migrating into the allantois, and directly into the adjacent embryonic endoderm. Time-lapse analysis shows these cells to be actively migratory from the time they exit the primitive streak.

Alkaline Phosphatase↗
PubMed2000

The role of cadherins during primordial germ cell migration and early gonad formation in the mouse.

Primordial germ cells (PGCs) are the founder cells of the gametes. In mammals, PGCs migrate from the hindgut to the genital ridges, where they coalesce with each other and with somatic cells to form the primary sex cords. We show here that, in both sexes, PGCs express P- and E-cadherins during and after migration, and N-cadherin at post-migratory stages. E-Cadherin is not expressed by PGCs whilst in the hindgut, but is upregulated as they leave. Blocking antibodies against E-, but not P-cadherin cause defective PGC-PGC coalescence, and in some cases, ectopic PGCs.

Animals↗