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Biomedical subjects

J A Saunders

Publications and source records attributed to J A Saunders.

At least 19 recordsLinked to original sources
PubMed2006

Post-acute dispositions of older adults hospitalized for depression.

This study addressed factors associated with six-month post-acute dispositions (continuous community stay, medical hospitalization, psychiatric rehospitalization, nursing home placement, death) for older adults hospitalized for depression and discharged to the community. The sample included 199 older adults; and data were collected via medical records, interviews with discharge planners, patients, and family members. Over half of the sample remained in the community throughout the observation period; 23% experienced psychiatric re-admission and 10% entered a nursing home. Several factors associated with nursing home placement were identified: less improvement in depression during the hospitalization, lower Global Assessment of Functioning (GAF) scores at discharge; and less mental health service use in the post-acute period. Those at higher risk of psychiatric re-admission had more previous psychiatric hospitalizations and were marginally more likely to be married and have lower Brief Psychiatric Rating Scale (BPRS) scores at discharge. Differentiating those at risk for nursing home placement may be easier than differentiating those at risk of psychiatric readmission.

Aftercare↗
PubMed2005

Physics-based protein-structure prediction using a hierarchical protocol based on the UNRES force field: assessment in two blind tests.

Recent improvements in the protein-structure prediction method developed in our laboratory, based on the thermodynamic hypothesis, are described. The conformational space is searched extensively at the united-residue level by using our physics-based UNRES energy function and the conformational space annealing method of global optimization. The lowest-energy coarse-grained structures are then converted to an all-atom representation and energy-minimized with the ECEPP/3 force field. The procedure was assessed in two recent blind tests of protein-structure prediction. During the first blind test, we predicted large fragments of alpha and alpha+beta proteins [60-70 residues with C(alpha) rms deviation (rmsd) <6 A]. However, for alpha+beta proteins, significant topological errors occurred despite low rmsd values. In the second exercise, we predicted whole structures of five proteins (two alpha and three alpha+beta, with sizes of 53-235 residues) with remarkably good accuracy. In particular, for the genomic target TM0487 (a 102-residue alpha+beta protein from Thermotoga maritima), we predicted the complete, topologically correct structure with 7.3-A C(alpha) rmsd. So far this protein is the largest alpha+beta protein predicted based solely on the amino acid sequence and a physics-based potential-energy function and search procedure. For target T0198, a phosphate transport system regulator PhoU from T. maritima (a 235-residue mainly alpha-helical protein), we predicted the topology of the whole six-helix bundle correctly within 8 A rmsd, except the 32 C-terminal residues, most of which form a beta-hairpin. These and other examples described in this work demonstrate significant progress in physics-based protein-structure prediction.

Amino Acid Sequence↗
PubMed2004

The protein folding problem: global optimization of the force fields.

The evolutionary development of a theoretical approach to the protein folding problem, in our laboratory, is traced. The theoretical foundations and the development of a suitable empirical all-atom potential energy function and a global optimization search are examined. Whereas the all-atom approach has thus far succeeded for relatively small molecules and for alpha-helical proteins containing up to 46 residues, it has been necessary to develop a hierarchical approach to treat larger proteins. In the hierarchical approach to single- and multiple-chain proteins, global optimization is carried out for a simplified united residue (UNRES) description of a polypeptide chain to locate the region in which the global minimum lies. Conversion of the UNRES structures in this region to all-atom structures is followed by a local search in this region. The performance of this approach in successive CASP blind tests for predicting protein structure by an ab initio physics-based method is described. Finally, a recent attempt to compute a folding pathway is discussed.

Algorithms↗
PubMed2002

Ab initio folding of multiple-chain proteins.

Our previous methodology for ab initio prediction of protein structure is extended here to treat multiple-chain proteins. This involved modification of our united-residue (UNRES) force field and our Conformational Space Annealing (CSA) Global Optimization procedure. Good results have been obtained for both a four- and a three-helix protein from the CASP3 exercise.

Dimerization↗
PubMed2001

Perception of 3D surface orientation from skew symmetry.

In this paper, we investigate how symmetry can be used to perceive 3D surface orientation. When a symmetric planar object is viewed from an angle, the projected contour has skew symmetry, which provides partial information about the 3D orientation of the object. For a given skew symmetry, this information can be characterized by a constraint curve of possible slant/tilt combinations that are consistent with a mirror-symmetric interpretation. These constraint curves move around when an object is rotated within a plane, and depend on what we will term the spin of the object: the angle between its axis of symmetry and the direction of tilt. To test the influence of symmetry constraint curves, we presented subjects with stereo images of symmetric objects that varied in spin, and had them perform an orientation-matching task. We found that the judgments showed biases that depended on the spin of the objects. Since other sources of information depend only on slant and tilt, not on spin, the biases imply that skew symmetry contributed to subjects' judgments. In a second experiment, we introduced conflicts between stereo and symmetry cues, and found that the spin-dependent biases can be modulated by selectively changing stereo slant. We propose an explanation of these results involving the optimal integration of stereo and skew symmetry, and present a Bayesian model that can account for the pattern of biases.

Analysis of Variance↗
PubMed2000

Detection of plant genes using a rapid, nonorganic DNA purification method.

We have developed a simple procedure for the preparation of plant genomic DNA using FTA paper. Plant leaves were crushed against FTA paper, and the genomic DNA was purified using simple, nonorganic reagents. The 18S rRNA gene and the gene encoding the ribulose-1, 5-bisphosphate carboxylase/oxygenase large subunit (rbcL) from the chloroplast genome were detected by PCR amplification of DNA on FTA paper. DNA amplification was successful using extracts from 16 dicot and monocot plants. Studies of specific plant extracts revealed that extracts of leaf samples could be collected and stored at room temperature on FTA paper without a decrease in the DNA amplification success rate for more than a month. Both the 18S RNA gene and the rbcL gene were detected in the genomic DNA isolated from various soybean cultivars stored in this manner. Furthermore, by modestly increasing the number of cycles of DNA amplification, we were able to detect the uidA gene in transgenic tobacco and rice leaves as well as a single copy gene linked to the resistance gene of cyst nematode race 3 using genomic DNA isolated on FTA paper. These results demonstrate that genomic DNA isolated using FTA paper can be used for the detection of plant genes, from a wide range of plants with either high or low gene copy number and of either nuclear or cytoplasmic origin.

Base Sequence↗
PubMed2000

Intracellular trafficking of pigeon beta-very low density lipoprotein and low density lipoprotein at low and high concentrations in pigeon macrophages.

Foam cell formation occurs in vitro at lipoprotein concentrations above 50 microgram/ml in pigeon macrophages. Hypothetically, intracellular trafficking of lipoproteins at higher concentrations may differ from uptake of lipoproteins associated with low concentrations, revealing a separate atherogenic endocytic pathway. Macrophage intracellular trafficking of pigeon beta-very low density lipoprotein (beta-VLDL) and low density lipoprotein (LDL) at low concentrations (12 microgram/ml) near the saturation of high affinity binding sites and high lipoprotein concentrations (50-150 microgram/ml) used to induce foam cell formation were examined. Pigeon beta-VLDL and LDL, differentially labeled with colloidal gold, were added simultaneously to contrast trafficking of beta-VLDL, which causes in vitro foam cell formation, with LDL, which does not. The binding of lipoproteins to cell surface structures, distribution of lipoproteins in endocytic organelles, and the extent of colabeling in the endocytic organelles were determined by thin-section transmission electron microscopy. At low concentrations, the intracellular trafficking of pigeon LDL and beta-VLDL was identical. At high concentrations, LDL was removed more rapidly from the plasma membrane and reached lysosomes more quickly than beta-VLDL. No separate endocytic route was present at high concentrations of beta-VLDL; rather, an increased residence on the plasma membrane, association with nonmicrovillar portions of the plasma membrane, and slower trafficking in organelles of coated-pit endocytosis reflected a more atherogenic trafficking pattern.

Animals↗
PubMed1995

Rapid optimization of electroporation conditions for plant cells, protoplasts, and pollen.

The optimization of electroporation conditions for maximal uptake of DNA during direct gene transfer experiments is critical to achieve high levels of gene expression in transformed plant cells. Two stains, trypan blue and fluorescein diacetate, have been applied to optimize electroporation conditions for three plant cell types, using different square wave and exponential wave electroporation devices. The different cell types included protoplasts from tobacco, a stable mixotrophic suspension cell culture from soybean with intact cell walls, and germinating pollen from alfalfa and tobacco. Successful electroporation of each of these cell types was obtained, even in the presence of an intact cell wall when conditions were optimized for the electroporation pulse. The optimal field strength for each of these cells differs, protoplasts having the lowest optimal pulse field strength, followed by suspension cells and finally germinating pollen requiring the strongest electroporation pulse. A rapid procedure is described for optimizing electroporation parameters using different types of cells from different plant sources.

Electroporation↗
PubMed1995

Perceiving heading in the presence of moving objects.

In most models of heading from optic flow a rigid environment is assumed, yet humans often navigate in the presence of independently moving objects. Simple spatial pooling of the flow field would yield systematic heading errors. Alternatively, moving objects could be segmented on the basis of relative motion, dynamic occlusion, or inconsistency with the global flow, and heading determined from the background flow. Displays simulated observer translation toward a frontal random-dot plane, with a 10 deg square moving independently in depth. The path of motion of the object was varied to create a secondary focus of expansion (FOE') 6 deg to the right or left of the actual heading point (FOE), which could bias the perceived heading. There was no effect when the FOE was visible, but when the object moved in front of it, perceived heading was biased toward the FOE' by approximately 1.9 degrees with a transparent object, and approximately 3.4 degrees with an opaque object. The results indicate that scene segmentation does not occur prior to heading estimation, which is consistent with spatial pooling weighted near the FOE. A simple template model based on large-field, center-weighted expansion units accounts for the data. This may actually represent an adaptive solution for navigation with respect to obstacles on the path ahead.

Analysis of Variance↗
PubMed1993

Construction of a reshaped HMFG1 antibody and comparison of its fine specificity with that of the parent mouse antibody.

A human antibody with milk mucin specificity was obtained by transferring the complementarity determining regions (CDR) of the mouse antibody HMFG1 onto carefully selected human framework regions. The resulting reshaped human antibody, HuHMFG1, showed no difference in relative affinity for its antigen compared with the parent mouse HMFG1. The minimum epitope recognized by both the mouse and reshaped antibodies was demonstrated by epitope mapping to be identical, and consists of the tetramer PDTR. In a replacement net analysis, in which each of the amino acids was replaced in turn with the 19 other residues, it was determined that mouse HMFG1 and HuHMFG1 reacted with this series of synthetic peptides in an equivalent manner, indicating retention of identical fine specificity in the HuHMFG1 antibody. In contrast to other published reports, this was achieved without involvement of any framework residues in the binding site transfer. These data demonstrate that if well-matching human framework regions are employed grafting the CDR only can be sufficient to confer desired specificities to human antibodies and can, indeed, provide human analogues of mouse antibodies with virtually indistinguishable affinities and fine specificities relative to the mouse parent antibodies.

Amino Acid Sequence↗
PubMed1992

Electrofusion and electroporation of plants.

The utilization of electrofusion and electroporation techniques has had a major impact on the genetic manipulation of plants within the last decade. This review of the development of electrofusion and electroporation, as it applies to plants, highlights major developmental aspects of this technology. These include mechanisms for cell fusion, molecular exchange, and parameters that affect the efficiency of fusion and electroporation.

Journal Article↗
PubMed1990

Drug therapy in pregnancy: the lessons of diethylstilbestrol, thalidomide, and bendectin.

A pregnant woman and the fetus she carries face health risks from many sources. One risk that requires ongoing vigilance is the use of prescription drugs during pregnancy. The international health care community has been sensitized to the risks of drug use during pregnancy because of three pharmaceuticals that have caused widespread crises for mothers and their offspring. The crises that diethylstilbestrol, thalidomide, and, to a lesser extent, Bendectin have created in the past four decades are reviewed in this article. The lessons these drug crises can teach us are articulated in the belief that similar crises may be averted in the future.

Abnormalities, Drug-Induced↗
PubMed1989

Advanced breast cancer. A randomised trial of epidoxorubicin at two different dosages and two administration systems.

Sixty-two women with advanced breast cancer have been entered into a randomised trial comparing bolus injection with 24-h infusion of epirubicin given as a dose of either 20 mg or 40 mg weekly, of which 57 patients are eligible for analysis. Bolus injection proved significantly more successful than prolonged infusion in response rate, time to first event and survival. No significant differences appeared between the two doses using these measures, however 40 mg weekly was significantly more toxic than 20 mg weekly. Epirubicin given as a weekly 20 mg bolus injection appears both effective and relatively free from toxicity.

Breast Neoplasms↗
PubMed1989

Prospective evaluation of a low maintenance policy for semipermanent silicone vascular access catheters.

Twenty-six women had semipermanent vascular access catheters (VACs) inserted to allow weekly outpatient infusion chemotherapy for advanced breast cancer. VACs were maintained without occlusive dressings, antibiotics, repeated flushings or heparin for a total of 2294 patient days (range 6 to 217 days, median 55 days). Three exit site and one subcutaneous tunnel infection occurred but no patient suffered septicaemia. VACs allowed both blood sampling and drug administration on 267 occasions and drug administration only on 19 occasions. No catheter became completely occluded.

Breast Neoplasms↗
PubMed1988

Simplifying infusion chemotherapy: preliminary communication.

A low-intervention policy for Hickman catheter maintenance has been evaluated and found to be safe and cost effective. A simple, lightweight, disposable device has been used for 24-hour ambulatory home infusion. Implementation of this policy as part of a prospective randomized trial of single-agent chemotherapy in advanced breast cancer has demonstrated that slow intravenous infusion reduces the acute toxicity of epirubicin when compared with bolus injection.

Breast Neoplasms↗