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Biomedical subjects

M A Shifman

Publications and source records attributed to M A Shifman.

14 recordsLinked to original sources

Molecular dynamics simulation on a network of workstations using a machine-independent parallel programming language.

Molecular dynamics simulations investigate local and global motion in molecules. Several parallel computing approaches have been taken to attack the most computationally expensive phase of molecular simulations, the evaluation of long range interactions. This paper reviews these approaches and develops a straightforward but effective algorithm using the machine-independent parallel programming language, Linda. The algorithm was run both on a shared memory parallel computer and on a network of high performance Unix workstations. Performance benchmarks were performed on both systems using two proteins. This algorithm offers a portable cost-effective alternative for molecular dynamics simulations. In view of the increasing numbers of networked workstations, this approach could help make molecular dynamics simulations more easily accessible to the research community.

Algorithms

PFGE MAPPER and PFGE READER: two tools to aid in the analysis and data input of pulse field gel electrophoresis maps.

Pulse field gel electrophoresis mapping is an important technique for characterizing large segments of DNA. We have developed two tools to aid in the construction of pulse field electrophoresis gel maps: PFGE READER which stores experimental conditions and calculates fragment sizes and PFGE MAPPER which constructs pulse field gel electrophoresis maps.

Clinical Laboratory Information Systems

CHROMINFO: a database for viewing and editing top-level chromosome data.

CHROMINFO is a prototype database that is intended to serve as a liaison tool for researchers working in different centers on mapping of the same mammalian chromosome. It provides a bird's-eye-view of top-level entities on a chromosome (such as gene loci, chromosome breakpoints and contigs) and relates them to one another in one dimension, the axis of the chromosome. Consensus data can be entered, edited, queried and displayed in a variety of ways. Summary evidence for consensus data can also be stored and retrieved. Information may be downloaded from the Genome Data Base periodically, and order and distance information is then incorporated. The prototype of CHROMINFO was built for human chromosome 16. Versions have been created for several other chromosomes.

Alleles

Analysis of phospholipids in human amniotic fluid by 31P NMR.

A recently described solvent-reagent system for obtaining narrow linewidths in 31P NMR spectra of phospholipid extracts was applied to human amniotic fluid. Resolution of the major components was achieved by manipulating the solvent composition, and assignments were made by spiking samples with standard compounds. Spin-lattice relaxation times were determined and used to optimize data acquisition. NMR estimates of the phosphatidylcholine to sphingomyelin ratio for 33 patients were compared to those obtained by TLC densitometry, a common clinical assay for fetal pulmonary maturity. Estimates of the levels of phosphatidylglycerol and phosphatidylinositol could also be obtained from 31P NMR. High-resolution 31P NMR in this solvent-reagent system provides a relatively straightforward and reliable alternative method for assessing fetal pulmonary status by phospholipid quantitation in human amniotic fluid. The 31P NMR method has the advantage that it is sensitive to total, and not just unsaturated, phosphatidylcholine.

Amniotic Fluid

Modeling uncertainty in a database for physical gene mapping data.

We are building a database for the storage, retrieval, and graphical display of physical gene mapping data. To allow this information to be analyzed robustly, such a database must confront the inherent uncertainty of the data as a central design issue. The paper describes the overall database design, the types of gene mapping data which the system will contain, the types of uncertainty in the data, and certain of the design issues involved in allowing the database to handle uncertainty in a comprehensive fashion. Only if a full appreciation of uncertainty is built into the system from its inception will a physical gene mapping database be truly robust and successful.

Chromosome Mapping

Molecular dynamics simulation on a network of workstations using a machine-independent parallel programming language.

Molecular dynamics simulations investigate local and global motion in molecules. Several parallel computing approaches have been taken to attack the most computationally expensive phase of molecular simulations, the evaluation of long range interactions. This paper develops a straightforward but effective algorithm for molecular dynamics simulations using the machine-independent parallel programming language, Linda. The algorithm was run both on a shared memory parallel computer and on a network of high performance Unix workstations. Performance benchmarks were performed on both systems using two proteins. This algorithm offers a portable cost-effective alternative for molecular dynamics simulations. In view of the increasing numbers of networked workstations, this approach could help make molecular dynamics simulations more easily accessible to the research community.

Algorithms

A critical evaluation of the manual/visual differential leukocyte counting method.

The performance of differential leukocyte counting by 73 technologists and technicians working in 5 different laboratories in a large medical center was evaluated. Good correlation with the reference method was found for neutrophils, normal lymphocytes, and eosinophils. More variability was noted in the estimation of stab neutrophils and variant (atypical) lymphocytes and monocytes. The sensitivity of this method for clinically important conditions ranged from 100% to 34%, depending upon the abnormality.

Evaluation Studies as Topic

A flagging system for multichannel hematology analyzers.

A flagging system to identify blood specimens requiring a blood film review and/or differential leukocyte count is described. Its utility in avoiding unnecessary differential counts particularly in outpatients is given. Significant reductions in workload can be anticipated without deterioration of patient care.

Anemia

Hepatocyte receptors for antithrombin III-proteinase complexes.

The in vivo clearance of antithrombin III-proteinase complexes occurs via a specific and saturable pathway located on hepatocytes. We now report studies of the catabolism of antithrombin III-proteinase complexes in vitro using rat hepatocytes in primary culture. Antithrombin III-thrombin and trypsin complexes were prepared and purified to homogeneity. Ligand uptake by hepatocytes was concentration, temperature, and time dependent. Initial rate studies were performed to characterize the maximum rate of uptake, V, and apparent Michaelis constant Kapp. These studies yielded a V of 12.8 fmol/mg cell protein/min and a Kapp of 144 nM for antithrombin-trypsin complexes. Competition experiments with antithrombin III, antithrombin III-proteinase complexes, alpha 2-macroglobulin-methylamine, asialoorosomucoid and the neoglycoproteins, fucosyl-bovine serum albumin (BSA), N-acetylglucosaminyl-BSA, and mannosyl-BSA indicated that only antithrombin III-proteinase complexes were recognized by the hepatocyte receptor. Uptake studies were performed at 37 degrees C with 125I-antithrombin III-trypsin and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) in conjunction with autoradiography. These studies demonstrate time-dependent uptake and degradation of the ligand to low molecular weight peptides. In addition, there was a time-dependent accumulation of a high molecular weight complex of ligand and a cellular protein. This complex disappeared when gels were performed under reducing conditions.

Animals

Venous thrombosis in a family with defective release of vascular plasminogen activator and elevated plasma factor VIII/von Willebrand's factor.

A family is described in which venous thrombosis developed in five members as early as 14 years of age. Routine coagulation studies, plasma antithrombin III, factor V, plasminogen, beta-thromboglobulin, fibrinopeptide A, prothrombin fragment F1+2, and thrombin-antithrombin III complex were all within normal limits. However, defective release of vascular plasminogen activator was observed on several occasions in all five subjects as compared with a control population of 125 persons (0.04 Committee on Thrombolytic Agents [CTA] units/ml plasma as compared with 0.21 CTS units/ml). In addition, levels of factor VII/von Willebrand's factor were significantly elevated above the normal range in this pedigree.

Adolescent

In vivo catabolism of alpha 1-proteinase inhibitor-trypsin, antithrombin III-thrombin and alpha 2-macroglobulin-methylamine.

The clearances of 125I-labeled alpha 1-proteinase inhibitor-trypsin, antithrombin III-thrombin and alpha 2-macroglobulin-methylamine (CH3NH2) were compared in our previously described mouse model. alpha 1-Proteinase inhibitor-trypsin cleared with a t 1/2 of 20 min, antithrombin III-thrombin of 7 min and 125I-labeled alpha 2-macroglobulin-methylamine of 2 min. Competition studies were performed to determine whether one or several pathways clear these three ligands. The clearance of 125I-labeled alpha 1-proteinase inhibitor-trypsin and 125I-labeled antithrombin III-thrombin was blocked by large molar excesses of either ligand, but not by alpha 2-macroglobulin-methylamine. The clearance of 125I-labeled alpha 2-macroglobulin-methylamine can be blocked by a large molar excesses of unlabeled alpha 2-macroglobulin-methylamine but not by alpha 1-proteinase inhibitor-trypsin. These studies demonstrate that the clearance of alpha 1-proteinase inhibitor-trypsin complexes is independent of alpha 2-macroglobulin-methylamine and utilizes the same pathway which is involved in the clearance of antithrombin III-thrombin complexes.

Animals

A colorimetric assay for releasable plasminogen activator.

We describe an equilibrium assay for measuring release of plasminogen activator form blood-vessel walls and report data from 125 individuals free of overt thromboembolic disease. Excess human plasminogen is added to the euglobulin fraction of plasma obtained before and after venous occlusion at mean systolic pressure. To measure plasmin generation in these samples, we used the chromogenic plasmin substrate D-Val-Leu-Lys-p-nitroanilide, which liberates p-nitroaniline upon cleavage. Releasable plasminogen activator in 24 subjects was determined by this colorimetric assay and by the radiocasein assay previously reported by this laboratory (Am. J. Clin. Pathol. 76,403-409, 1981), and the results were compared. The correlation coefficient was 0.97. The colorimetric assay offers several advantages over the radiocasein assay: shorter incubation (6 vs 16 h) and no preparation or quantification of a radioactive substrate and its cleavage products.

Adult

Evaluation of a centrifugal blood cell processor for washing platelet concentrates.

A semiautomated saline wash procedure using a blood cell processor was evaluated as a technique for removing plasma from platelet concentrates. In vitro studies demonstrated 92 to 99.6 percent (mean, 96%) removal of total plasma protein (n = 30) with 84 to 97 percent (mean, 90.8%) platelet recovery (n = 28) in post-wash units. Post-wash pH values changed by +0.2 to -0.86 (mean, -0.47) (n = 30); the level of recovery from hypotonic shock was 69 to 97 percent (mean, 86%) (n = 11) of pre-wash units; weighted morphology scores decreased from a mean of 248 to 223 (n = 9). Aggregation response to arachidonic acid, collagen, and adenosine diphosphate plus epinephrine showed essentially no change following the wash procedure, and electron microscopy demonstrated slight morphologic alteration. Autologous platelets labeled with indium-111 demonstrated 43 +/- 20 percent recovery (n = 11) for washed units, compared to 41 +/- 10 percent for control unwashed units (n = 5); mean survivals were 140 +/- 41 hours (n = 11) for washed platelets and 185 +/- 28 hours for unwashed units (n = 5). Thirteen alloimmunized patients receiving 55 washed platelet concentrates demonstrated a mean 1- to 4-hour corrected count increment of 3.99 X 10(3) per microliter, compared to 3.02 X 10(3) per microliter for 77 unwashed platelet units given to the same patients. This study documents that platelet concentrates maintain viability and efficacy following a semiautomated saline wash method using the Cobe 2991 Blood Cell Processor, a technique that may be helpful for patients who require plasma-depleted platelet transfusions.

Blood Platelets

TREACT. An expert system consultation program to aid in the diagnosis of transfusion reactions.

We have developed a rule-based, expert system consultation program, TREACT, to aid in the diagnosis of transfusion reactions. Given clinical signs, symptoms, and laboratory results, the program generates diagnoses, alerts the user when a medical director should be called, suggests follow-up actions, and makes recommendations for future transfusion. Diagnoses made by TREACT, including 121 reactions, were compared with those of the medical directors over a 6-month period. The overall diagnostic concordance between the medical directors and the program was 0.777. When this was corrected for chance association (kappa statistic), the concordance was 0.703 (p less than 0.0001), which can be interpreted on a qualitative scale as substantial agreement. The program has also been used successfully as a tool for training new technologists. Other advantages and possibilities that expert systems offer to transfusion medicine are discussed.

Diagnosis, Computer-Assisted