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Biomedical subjects

A Adams

Publications and source records attributed to A Adams.

At least 73 records · Page 4Linked to original sources
PubMed1999

Crystal structure of the topoisomerase II poison 9-amino-[N-(2-dimethylamino)ethyl]acridine-4-carboxamide bound to the DNA hexanucleotide d(CGTACG)2.

The structure of the complex formed between d(CGTACG)(2) and the antitumor agent 9-amino-[N-(2-dimethylamino)ethyl]acridine-4-carboxamide has been solved to a resolution of 1.6 A using X-ray crystallography. The complex crystallized in space group P6(4) with unit cell dimensions a = b = 30.2 A and c = 39.7 A, alpha = beta = 90 degrees, gamma = 120 degrees. The asymmetric unit contains a single strand of DNA, 1. 5 drug molecules, and 29 water molecules. The final structure has an overall R factor of 19.3%. A drug molecule intercalates between each of the CpG dinucleotide steps with its side chain lying in the major groove, and the protonated dimethylamino group partially occupies positions close to ( approximately 3.0 A) the N7 and O6 atoms of guanine G2. A water molecule forms bridging hydrogen bonds between the 4-carboxamide NH and the phosphate group of the same guanine. Sugar rings adopt the C2'-endo conformation except for cytosine C1 which moves to C3'-endo, thereby preventing steric collision between its C2' methylene group and the intercalated acridine ring. The intercalation cavity is opened by rotations of the main chain torsion angles alpha and gamma at guanines G2 and G6. Intercalation perturbs helix winding throughout the hexanucleotide compared to B-DNA, steps 1 and 2 being unwound by 8 degrees and 12 degrees, respectively, whereas the central TpA step is overwound by 17 degrees. An additional drug molecule, lying with the 2-fold axis in the plane of the acridine ring, is located at the end of each DNA helix, linking it to the next duplex to form a continuously stacked structure. The protonated N,N-dimethylamino group of this "end-stacked" drug hydrogen bonds to the N7 atom of guanine G6. In both drug molecules, the 4-carboxamide group is internally hydrogen bonded to the protonated N-10 atom of the acridine ring. The structure of the intercalated complex enables a rationalization of the known structure-activity relationships for inhibition of topoisomerase II activity, cytotoxicity, and DNA-binding kinetics for 9-aminoacridine-4-carboxamides.

Acridines↗
PubMed1999

L-764406 is a partial agonist of human peroxisome proliferator-activated receptor gamma. The role of Cys313 in ligand binding.

Insulin-sensitizing thiazolidinedione (TZD) compounds are high affinity ligands for a member of the nuclear receptor family, peroxisome proliferator-activated receptor (PPAR) gamma. A scintillation proximity assay for measurement of 3H-radiolabeled TZD binding to human PPARgamma under homogeneous conditions was developed. Using this approach, a novel non-TZD compound (L-764406) was shown to be a potent (apparent binding IC50 of 70 nM) PPARgamma ligand. Preincubation of PPARgamma with L-764406 prevented binding of the [3H]TZD, suggesting a covalent interaction with the receptor; in addition, structurally related analogues of L-764406, which would be predicted not to interact with PPARgamma in a covalent fashion, did not displace [3H]TZD binding to PPARgamma. Covalent binding of L-764406 was proven by an observed molecular weight shift of a tryptic PPARgamma ligand binding domain (LBD) peptide by mass spectrometric analysis. A specific cysteine residue (Cys313 in helix 3 of hPPARgamma2) was identified as the attachment site for this compound. In protease protection experiments, the liganded receptor adopted a typical agonist conformation. L-764406 exhibited partial agonist activity in cells expressing a chimeric receptor containing the PPARgamma LBD and a cognate reporter gene and also induced the expression of the adipocyte-specific gene aP2 in 3T3-L1 cells. In contrast, L-764406 did not exhibit activity in cells transfected with chimeric receptors containing PPARalpha or PPARdelta LBDs. The partial agonist properties of L-764406 were also evident in a co-activator association assay, indicating that the increased transcription in cells was co-activator mediated. Thus, L-764406 is a novel non-TZD ligand for PPARgamma and is also the first known partial agonist for this receptor. The results suggest a critical functional role for Cys313, and helix 3, in contributing to ligand binding and subsequent agonist-induced conformational changes.

Amino Acid Sequence↗
PubMed1999

The patient exit interview as an assessment of physician-delivered smoking intervention: a validation study.

In evaluating the efficacy of physician-delivered counseling interventions for health behavior changes such as smoking cessation, a major challenge is determining the degree to which interventions are implemented by physicians. The Patient Exit Interview (PEI; J. Ockene et al., 1991) is a brief measure of a patient's perception of the content and quantity of smoking cessation intervention received from his or her physician. One hundred eight current smokers seen in a primary care clinic completed a PEI following their physician visit. Participants were 45% male, 95% Caucasian, with a mean age of 42 years and an average of 22 years of smoking. The PEI correlated well with a criterion measure of an audiotape assessment of the physician-patient interaction (r = .67, p < .001). When discrepancy occurred, in general it was due to patients' over-reporting of intervention as compared with the criterion measure. Implications and limitations of these findings are discussed.

Adult↗
PubMed1999

Determination by MAD-DM of the structure of the DNA duplex d[ACGTACG(5-BrU)]2 at 1.46 A and 100 K.

A four-wavelength MAD experiment on a new brominated octanucleotide is reported here. d[ACGTACG(5-BrU)], C77H81BrN30O32P7, Mr (DNA) = 2235, tetragonal, P43212 (No. 96), a = 43.597, c = 26.268 A, V = 49927.5 A3, Z = 8, T = 100 K, R = 10.91% for 4312 reflections between 15.0 and 1.46 A resolution. The self-complementary brominated octanucleotide d[ACGTACG(5-BrU)]2 has been crystallized and data measured to 1.45 A at both 293 K and a second crystal flash frozen at 100 K. The latter data collection was carried out to the same resolution at the four wavelengths 0.9344, 0.9216, 0.9208 and 0.9003 A, around the Br K edge at 0.92 A and the structure determined from a map derived from a MAD data analysis using pseudo-MIR methodology, as implemented in the program MLPHARE. This is one of the first successful MAD phasing experiments carried out at Sincrotrone Elettra in Trieste, Italy. The structure was refined using the data measured at 0.9003 A, anisotropic temperature factors and the restrained least-squares refinement implemented in the program SHELX96, and the helical parameters are compared with those previously determined for the isomorphous d(ACGTACGT)2 analogue. The asymmetric unit consists of a single strand of octamer with 96 water molecules. No countercations were located. The A-DNA helix geometry obtained has been analysed using the CURVES program.

Carbohydrate Conformation↗
PubMed1999

Results of small incision extracapsular cataract surgery using the anterior chamber maintainer without viscoelastic.

AIMS: To assess the efficacy of extracapsular cataract surgery using the anterior chamber maintainer (ACM) without the use of viscoelastic. To compare the effects of this surgical technique on non-diabetic and diabetic patients. METHODS: A prospective single armed clinical trial of 46 eyes in 46 patients undergoing cataract surgery using the ACM without viscoelastic. Patients were assessed preoperatively and at 3 weeks, 3 months, and 12 months postoperatively. The main outcome variables included visual acuity, surgically induced astigmatic change (SIAC), changes in endothelial cell density (ECD), and morphology affecting the central and superior regions of the cornea. RESULTS: Postoperatively, 56% and 70% of patients had unaided visual acuities of 6/12 or better at 3 weeks and 3 months respectively. Even after excluding those patients with pre-existing maculopathy (including diabetic maculopathy), there remains a significant difference between the non-diabetic and diabetic groups in terms of the proportion of patients attaining an unaided visual acuity of 6/12 or better at both 3 weeks (p = 0.003) and 3 months (p = 0.001). Three months postoperatively, the SIAC based upon the keratometric and refractive data was 1.1 dioptres (D) and 1.3 D respectively. There was no statistically significant difference in the SIAC when the non-diabetic and diabetic groups were compared. The mean central and superior endothelial cell losses at 3 months postoperatively were 16% and 22% respectively and at 12 months postoperatively were 20% and 25% respectively. The diabetic group demonstrated greater endothelial cell losses and a more marked and protracted deviation of endothelial cell morphology from normality when compared with the non-diabetic group; however, the differences did not reach statistical significance. CONCLUSIONS: The efficacy of small incision cataract surgery using the ACM in terms of visual outcome and induced astigmatism is comparable with the results obtained using other techniques that utilise a similar size of incision. However, in view of the magnitude and range of the endothelial cell losses associated with this technique the concurrent use of viscoelastic is suggested. There does not appear to be a statistically or clinically significant difference between non-diabetic and diabetic patients in terms of the magnitude of the endothelial cell losses or in the wound healing response in the 12 months after cataract surgery using the ACM.

Aged↗
PubMed1999

Borrowed buildings: Canada's temporary hospitals during World War I.

This article explores the alterations and additions made to houses, colleges, and larger public buildings in their temporary use as convalescent homes for wounded Canadian soldiers during World War I. These ''borrowed buildings'' anticipated and emphasized three important characteristics of subsequent hospital architecture by suggesting that domestic environments enhanced healing, that hospitals should be accessible, and that patients should be segregated according to social status and disease. The broader implications of the study are that temporarily appropriated spaces contribute to the definition of many institutions and often act as arenas of resistance to established practices.

Architecture↗
PubMed1999

Mercy missions.

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Developing Countries↗
PubMed1999

[The DACA].

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Aminoacridines↗
PubMed1998

Design and fabrication of topologically complex, three-dimensional microstructures

Two concepts for use in the fabrication of three-dimensional (3D) microstructures with complex topologies are described. Both routes begin with a two-dimensional (2D) pattern and transform it into a 3D microstructure. The concepts are illustrated by use of soft lithographic techniques to transfer 2D patterns to cylindrical (pseudo-3D) substrates. Subsequent steps-application of uniaxial strain, connection of patterns on intersecting surfaces-transform these patterns into free-standing, 3D, noncylindrically symmetrical microstructures. Microelectrodeposition provides an additive method that strengthens thin metal designs produced by patterning, welds nonconnected structures, and enables the high-strain deformations required in one method to be carried out successfully.

Journal Article↗
PubMed1998

Electron microscope studies of the in vitro phagocytosis of Mycobacterium spp. by rainbow trout Oncorhynchus mykiss head kidney macrophages.

The cytological response of rainbow trout Oncorhynchus mykiss head kidney macrophages to ingested Mycobacterium spp. was examined in vitro. Mycobacterium marinum or Mycobacterium sp. TB267 isolated from snakehead fish Channa striata Bloch were opsonised with either fresh rainbow trout serum, serum which had been heat-inactivated, or rainbow trout antiserum against the extracellular products (ECP) of the 2 Mycobacterium spp. A monoclonal antibody against the ECP was also used as an opsonin. Suspensions of macrophages were prepared (1 ml of 1 x 10(7) cells ml-1), mixed with the opsonised bacteria (100 microliters of 2 x 10(9) ml-1), and incubated at 18 degrees C for 0.5, 1, 2, 4 or 6 h to allow phagocytosis to occur. A quantitative evaluation of the phagocytosis of the mycobacteria by the macrophages was carried out by electron microscopy. Macrophage phagosomes and their contents were examined and numbers of intact and partially degraded bacteria determined. Pre-labelling dense granules (secondary lysosomes) with ferritin enabled phagosome lysosome fusion to be identified and their frequency determined. Opsonisation of the mycobacteria was found to greatly enhance the phagocytic and killing activity of the rainbow trout macrophages.

Animals↗
PubMed1998

The effectiveness of warning signs in hazardous work places: cognitive and social determinants.

Recommendations have been made that good warning signs should have a number of components: an alerting word such as danger, then statements of the hazard, of its seriousness, of the probable consequences and of how to avoid the hazard. Responses from 40 blue-collar workers and 44 students were measured to five industrial warning signs to determine the extent to which these components determine estimated sign effectiveness and behavioural intentions of compliance. Each sign was presented in five versions; the original (which in each case omitted one or more of the components), a 'full' version in which missing components were generated and inserted, and versions omitting, in turn, the hazard, consequences, and instructions statements. Previous findings concerning the importance of the signal word were supported. When signs were seen singly there was no tendency for versions with components missing to be rated as poorer. Only when all versions were seen together was the 'full' version ranked as being better, a result which is taken as reflecting the demand characteristics of the method. The results argue against strict adherence to a formula requiring specified components in a sign. Data also supported the third person effect, indicating that respondents considered others to be more vulnerable to the hazard and less likely to comply with the sign than they themselves. The finding that social factors are of considerable importance in sign compliance is discussed.

Accidents, Occupational↗
PubMed1998

Chronic energy deficiency in women from rural Bangladesh: some socioeconomic determinants.

This paper explores a number of socioeconomic factors thought to explain the wide prevalence of undernutrition among rural Bangladeshi women. The 1992 baseline survey data of the BRAC-ICDDR,B Joint Research Project at Matlab were used. Anthropometry was performed on a random sub-sample of 1462 currently married, non-pregnant women between 15 and 49 years of age. Women's nutritional status was defined in terms of Body Mass Index (BMI = wt in kg/ht in m2). Compared with women from better-off households, the mean weight (41.2 vs 43.0 kg; p < 0.0001), mid-upper arm circumference (MUAC) (22.1 vs 22.7; p < 0.0001), and BMI (18.5 vs 19.1; p < 0.0001) of poor women were consistently lower. However, no significant difference in mean height was found between the two groups. The results showed that women aged more than 35 years are twice as likely to have a BMI < 18.5 compared with younger women. Both years of schooling received and socioeconomic status are found to be important predictors of women's BMI. Women who have received one or more years of formal education are nearly half as likely to suffer chronic energy deficiency (BMI < 18.5) than women with no schooling. Again, better-off women are found to be 0.77 times less likely to have chronic energy deficiency than women from poor households. The implications of these findings in improving the nutritional status of rural Bangladeshi women are discussed.

Adolescent↗
PubMed1998

Induction of apoptosis by the novel retinoid AHPN in human T-cell lymphoma cells involves caspase-dependent and independent pathways.

Retinoids play an important role in the control of lymphocyte function and homeostasis in the thymus. In this study, we show that the induction of growth arrest and apoptosis in a variety of T-cell lymphoma cell lines, including Jurkat and Molt-4 cells, is highly specific for the synthetic retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (AHPN) since all-trans retinoic acid (RA), the RAR-selective retinoid TTAB, the RXR-selective retinoid SR11217 and the retinoid SR11302 exhibiting selective anti-AP1 activity, do not induce apoptosis or cause growth arrest. These findings support the concept that the effects of AHPN on proliferation and induction of apoptosis are mediated by a novel signaling pathway. AHPN-induced apoptosis is associated with an induction of internucleosomal DNA-fragmentation, increased annexin V binding and a 30-fold stimulation of caspase-3-like activity. Overexpression of Bcl-2 in Molt-4 cells greatly inhibits the induction of apoptosis by AHPN as indicated by the inhibition of DNA-fragmentation, annexin V binding and caspase-3-like activity. However, Bcl-2 overexpression does not interfere with the ability of AHPN to cause growth arrest or accumulation of cells in the early S-phase of the cell cycle, indicating that the effects of AHPN on growth arrest can be uncoupled from the effects on apoptosis. The caspase inhibitor Z-VAD-FMK, at concentrations that totally block caspase activity, delays but does not prevent cell death and does not affect the accumulation of cells in the S-phase of the cell cycle. Our results show that induction of caspase-3-like activity plays an important role in the execution of AHPN-induced apoptosis but cells can undergo cell death in the absence of this activity suggesting that AHPN-induced cell death involves caspase-dependent and -independent mechanisms.

Amino Acid Chloromethyl Ketones↗
PubMed1998

Nursing organizational practice and its relationship with other features of ward organization and job satisfaction.

This paper describes a new classification of ward organizational practice in nursing. Data related to aspects of ward nursing practice were collected by postal survey from a nationally representative sample of 74 acute hospital wards, and subjected to hierarchical cluster analysis. The model which was deemed to best 'fit' the data, provided three types of ward practices, which have been named: 'devolved', 'two tier' and 'centralized' nursing. The distinguishing features of the three classifications are similar but not identical to accepted 'ideal types' of primary, team and functional systems. The relationships between wards in each of the three identified categories and other ward organizational practice processes of nursing care and job satisfaction are described.

Analysis of Variance↗
PubMed1998

Alcohol counseling: physicians will do it.

OBJECTIVE: To assess the use of a brief provider-delivered alcohol counseling intervention of 5 to 10 minutes with high-risk drinking patients by primary care provider* trained in the counseling intervention and provided with an office support system. DESIGN: A group randomized study design was used. Office sites were randomized to either a usual care or special intervention condition, within which physicians and patients were nested. The unit of analysis was the patient. SETTING: Primary care internal medicine practices affiliated with an academic medical center. PARTICIPANTS: Twenty-nine providers were randomized by practice site to receive training and an office support system to provide an alcohol counseling special intervention or to continue to provide usual care. INTERVENTION: Special intervention providers received 2 1/2 hours of training in a brief alcohol-counseling intervention and were then supported by an office system that screened patients, cued providers to intervene, and made patient education materials available as tip sheets. MEASUREMENTS AND MAIN RESULTS: Implementation of the counseling steps was measured by patient exit interviews (PEI) immediately following the patient visit. The interval between the date of training and the date of the PEI ranged from 6 to 32 months. Special intervention providers were twice as likely as usual care providers to discuss alcohol use with their patients. They carried out every step of the counseling sequence significantly more often than did usual care providers (p < .001). This intervention effect persisted over the 32 months of follow-up. CONCLUSIONS: Physicians and other health-care providers trained in a brief provider-delivered alcohol intervention will counsel their high-risk drinking patients when cued to do so and supported by a primary care office system.

Adult↗