Biomedical subjects

S R Simon

Publications and source records attributed to S R Simon.

At least 73 records · Page 4Linked to original sources

PubMed1990

Inhibitors directed to binding domains in neutrophil elastase.

Human neutrophil elastase (HNE) can be inhibited by unsaturated fatty acids, including oleic acid [Ashe, B. M., & Zimmerman, M. (1977) Biochem. Biophys. Res. Commun. 75, 194-199; Cook, L., & Ternai, B. (1988) Biol. Chem. Hoppe-Seyler 369, 627-631], but is not affected by saturated fatty acids. We have shown that the interaction of oleic acid with HNE can be characterized by two apparent inhibitory modes: a high-affinity mode (Ki = 48 +/- 3 nM), resulting in partial noncompetitive inhibition (87% residual activity), and a competitive inhibitory mode of lower affinity (Ki = 16 +/- 1 microM). Binding of oleate in the high-affinity mode induces a blue shift in the endogenous fluorescence arising from the tryptophan residues in HNE. This shift is maximal in the presence of 1 microM oleate; higher concentrations of fatty acid have no further effect on the fluorescence spectrum. The negatively charged fluorescent ester of oleic acid and hydroxypyrenetrisulfonate (HPTSoleate) interacts with HNE at an apparent single site (Ki = 44 +/- 3 nM), resulting in competitive inhibition. A blue shift in the emission maximum of the pyrene fluorescence at 410 nm and a decrease in the ratio of the intensities of the maximum at 388 and 410 nm indicate that upon binding to HNE the environment of the pyrene ring in HPTSoleate becomes more hydrophobic.(ABSTRACT TRUNCATED AT 250 WORDS)

Arginine↗

PubMed1990

ViVACCy--a drug schedule based on G2 blockade and prolonged infusion of multiple tubulin-binding agents. A pilot study.

A drug schedule has been devised based on a strategy of G2 blockade followed by prolonged infusion of tubulin-binding agents. The regimen consists of doxorubicin 32 mg/m2 i.v. and cyclophosphamide 320 mg/m2 i.v. on day 1 followed by vinblastine (0.3 to 1.2 mg/m2/day), cisplatin (3 to 12 mg/m2/day), and vincristine (0.04 to 0.16 mg/m2/day) by continuous intravenous infusion on days 5 to 12. Courses are repeated every 28 days. Eighteen patients with advanced solid tumors received 37 courses of chemotherapy in a pilot study to determine safe drug concentrations for the three-drug infusion for 7 days. Dose limiting toxicity was myelosuppression. Patients who received prior mitomycin-C experienced more profound thrombocytopenia than those who did not. Nonhematologic toxicities included mild nausea, vomiting, and transient elevations of serum alkaline phosphatase and serum creatinine. One patient with squamous cell carcinoma of the esophagus who erroneously received vincristine 0.8 mg/m2 instead of 0.08 mg/m2 for 4 1/2 days developed transient myalgia, ileus, and a transient peripheral neuropathy; the patient achieved a sustained complete remission for 15 months and died of unrelated causes. Minor responses and stable disease were seen in two patients with renal cell carcinoma (1 and 2.5 months), three patients with colorectal carcinoma (1.5, 2, and 4 months), and one patient with squamous cell carcinoma of the tongue (2 months). The ViVACCy drug regimen can be given without undue toxicity and may be active in solid tumors.

Adult↗

PubMed1990

QUAWDS: a composite diagnostic system for gait analysis.

QUAWDS is a system for interpreting human gait. This task is complex because patients usually have multiple faults, and there is significant interaction between the components in the system. QUAWDS interprets a gait study by integrating associational and qualitative models of knowledge into a diagnostic system, taking advantage of the subtasks each kind of model can perform efficiently and effectively. An abductive hypothesis assembler is used to coordinate the subtasks. The result is a diagnostic solution that is 'locally best', i.e., no single change to the answer will produce a better solution.

Artificial Intelligence↗

PubMed1989

Hematologic complications of gastric bypass for morbid obesity.

Of 530 patients who have had a gastric bypass operation for morbid obesity at Allegheny General Hospital, 41 had decreases in serum iron, vitamin B12, and/or folate levels. These abnormalities were detected eight months to eight years (median, two years) after the operation. The hemoglobin level ranged from 7.4 to 14.1 gm/dl at the time of detection, and mean corpuscular volume (MCV) ranged from 58 to 119 cu microns. The most common problem was combined iron and vitamin B12 deficiencies. Physicians should be aware that folate, vitamin B12, and iron deficiencies occur after gastric bypass, though the time to development is variable. Hemoglobin level and MCV are not predictive of these deficiencies.

Anemia, Hypochromic↗

PubMed1989

Early changes in gait and maximum knee torque following knee arthroplasty.

Fourteen knees in 11 individuals were studied before knee arthroplasty and at three and six months following surgery. Eleven of these knees were further evaluated at 12 months following surgery. At each evaluation, kinematic, electromyographic, and force plate data were gathered during level walking. Maximum knee extension and flexion torques were also determined. The greatest improvement in gait was noted in the first three postoperative months when velocity increased 13% and stride length increased 14%. After six months gait changes were negligible. Maximum knee torques in the osteoarthritic population were decreased at three months, then returned to preoperative levels at six months. In the rheumatoid population, maximum knee torques steadily increased up to six months following surgery. Gait abnormalities that persist at six months and beyond following knee arthroplasty appear to be most related to the presence of arthritis in joints other than in the operated knee(s).

Aged↗

PubMed1988

Copper deficiency and sideroblastic anemia associated with zinc ingestion.

Anemia and neutropenia developed in a man who took pharmacologic doses of supplemental zinc. Laboratory investigation showed high zinc level, hypocupremia, low ceruloplasmin level, and ringed sideroblasts. All resolved after withdrawal of zinc. Self-administered zinc appears to have caused severe copper deficiency, with secondary anemia and neutropenia. Physicians should be aware of this deleterious and completely reversible effect of megadose mineral therapy. Zinc ingestion or exposure should be considered in the differential diagnosis of unexplained anemia, leukopenia, or sideroblastic anemia.

Adult↗

PubMed1988

Postural adjustments associated with rapid voluntary arm movements. II. Biomechanical analysis.

Normal subjects performed bilaterally symmetric rapid elbow flexions or extensions ("focal movements") while standing. Specific patterns of electromyographic activity in leg and trunk muscles ("associated postural adjustments") were seen for each type of movement. The biomechanical significance of these postural adjustments was analysed by means of the ground reaction forces and motion of the various body segments. Experimental data were compared with that from a theoretical model of the body consisting of a six segment kinetic chain with rigid links. Distinct patterns of the ground reaction forces with elbow flexion were opposite in direction to those seen with elbow extension. Movements of the various body segments were small and specific for a certain focal movement. Dynamic perturbations arising from the arm movement in an anteroposterior direction were found to be compensated by postural adjustments, whereas vertical perturbations were not compensated. The muscular activity acting about different joints in the different movements was found to correlate with the predictions of activity needed to compensate for net joint reaction moments arising from the focal movement. Motion of the various body segments could be understood as resulting from the interplay of the net reaction moments and the net muscular moments at the different joints. Dynamic postural requirements are accomplished by a precise active compensation initiated before the focal movement.

Adult↗

PubMed1988

Progression of scoliosis after skeletal maturity in institutionalized adults who have cerebral palsy.

To study the natural history of scoliosis in institutionalized adults who have cerebral palsy, we reviewed retrospectively the cases of fifty-one patients. The patients were followed for at least four years (mean, 16.3 years; range, four to forty years) after they had reached skeletal maturity. The individuals in whom the curve eventually progressed the most had had the largest curves at the time of skeletal maturity. The rate of progression was 0.8 degree each year in the patients in whom the curve was less than 50 degrees at the time of skeletal maturity and 1.4 degrees in those in whom the curve was more than 50 degrees (p less than 0.04). The patients who had the largest curves at the time of skeletal maturity had spastic quadriplegia and either a thoracolumbar or a lumbar curve, and they were bedridden.

Activities of Daily Living↗

PubMed1987

Radiation-induced leiomyosarcoma of the great vessels presenting as superior vena cava syndrome.

A patient with a pleomorphic intravascular leiomyosarcoma of the great vessels of the neck and mediastinum presented clinically with a superior vena cava syndrome. A latent period of 29 years elapsed between receiving orthovoltage radiation to the neck and right side of chest to treat recurrent ganglioneuroblastoma, and the appearance of a leiomyosarcoma and subsequent recurrences. The patient underwent partial resection of the tumor, received adjunct chemotherapy, and was shown to be free of disease by clinical tests and by magnetic resonance imaging (MRI) 17 months after completion of chemotherapy. The criteria for the diagnosis of radiation-induced sarcomas are reviewed in relation to the present case. The critical role of magnetic resonance imaging in both the diagnosis and continued follow-up of the patient is described. This would appear to be the first reported case of radiation-induced intravascular leiomyosarcoma of the great vessels of the neck and mediastinum presenting as a superior vena cava syndrome.

Adult↗

PubMed1987

Purification and characterization of a connective-tissue-degrading metalloproteinase from the cytosol of metastatic melanoma cells.

A metalloproteinase with activity against type IV collagen, type I collagen and gelatin has been purified from the cytosol of a highly metastatic mouse melanoma by anion-exchange, zinc-chelated and lectin-affinity column chromatography. The purified enzyme has a molecular mass of approx. 59 kDa and on isoelectric focusing in two-dimensional gels produced three spots with apparent isoelectric points (pI) between 5.7 and 6.1. Enzymic activity with collagen, but not gelatin, substrates was latent, requiring activation by trypsin or organomercurials. Trypsin activation of this metalloproteinase was accompanied by a change in molecular mass, whereas autoactivation after 1 month's storage, was not. The degradation of types I and IV collagen by the melanoma enzyme yielded products of lower molecular masses than those yielded by mammalian collagenases, this characteristic thus differentiating this metalloproteinase from classical collagenases.

Animals↗

PubMed1987

Albumin modulates lateral assembly of fibrin polymers: evidence of enhanced fine fibril formation and of unique synergism with fibrinogen.

We identified a new property of human albumin. It enhances formation of fine fibril (or leptofibril) structures during fibrin gelation, and by nephelometric and electron microscopic measurements, this property is independent of and synergistic with that of fibrinogen. We examined fibrin aggregation using physiologic temperatures and pH and albumin:fibrin concentration ratios below those at which the known accelerating effect on fibrin aggregation occurs. An albumin concentration dependent decrease in gel turbidity maxima was consistently demonstrable in buffers containing or lacking (2-5 mM) CaCl2. This decrease was shown to be induced by albumin preparations which had been exposed to 2 mM ethylene-diaminetetraacetate disodium salt (EDTA), dialyzed, and tested in EDTA-free buffer. A delay in the onset of aggregation was also shown in calcium-lacking buffers by use of either reaggregating fibrin or fibrinogen aggregated with low (0.01-0.05 unit/mL) thrombin concentrations. Rates of fibrin aggregation as well as those of fibrinopeptide release were not affected by albumin, and the decrease in gel absorbance was demonstrable when solubilized fibrin was reaggregated at all final fibrin concentrations (0.2-4 microM) examined. Computed from wavelength dependence turbidity measurements (1 microM fibrin, I = 0.20), albumin decreased the average mass:length ratio from 8.24 X 10(11) to 4.26 X 10(11) daltons/cm, or from that of an approximately six to a three protofibril-thick strand. It also decreased the mean fibril radius from 48.5 to 36.4 nm but had no effect on fibril density. Electron microscopic measurements of cross-sectional fibril widths, performed on sections of glutaraldehyde-fixed gels, disclosed differences between albumin-containing and control gels which were significant by chi 2 analysis (P greater than 0.001). Fibril groups of 7-20- and 21-40-nm width together comprised 77% of fibrils formed in the presence of albumin (n = 251) compared to 30% of controls (n = 309). Conversely, coarser fibrils of 41-60- and 61-97-nm width together comprised 23% of fibrils formed in the presence of albumin and 70% of controls. This albumin effect was demonstrable by use of different monomeric albumin preparations including defatted, undefatted (unexposed and exposed to 60 degrees C, 10 h), chromatographically [gel exclusion and (diethylaminoethyl)cellulose] pure, S-(carboxymethyl)albumin, and S-(N-ethylsuccinimidyl)albumin. Chromatographically isolated albumin oligomers lacked this property, suggesting that a specific site(s) on albumin was (were) required.(ABSTRACT TRUNCATED AT 400 WORDS)

Fibrin↗

PubMed1987

Preoperative and postoperative gait analyses of patients undergoing great toe-to-thumb transfer.

Microvascular transfer of the great toe is a reliable method of thumb reconstruction for many patients, but the precise deficit incurred by elective amputation of the great toe has not been fully defined. Twelve patients who had this procedure were evaluated with preoperative and postoperative gait analyses and clinical examinations. The mean age was 29.3 years, with a mean clinical follow-up of 30.3 months, and a comparative follow-up gait study at a mean of 21.1 months postoperatively. Only one patient exhibited a significant motion change postoperatively, which was a reduction in ankle plantar-flexion at weight release of the operated foot (push-off). The average velocity, cadence, step length of the foot that had surgery performed, single and double limb stance times of each foot, and step width did not significantly change. There was only a slight average reduction in stride length at 4.6% (p less than 0.05), which resulted from a decrease in step length of the foot that did not have surgery 7.6% (p less than 0.02). Nine patients had no clinical complaints, two had occasional mild discomfort near the second and third metatarsal heads, and one had intolerance to cold.

Adolescent↗

PubMed1987

Femoral anteversion.

Biplane roentgenography, axial roentgenography, and fluoroscopy are the usual roentgenographic methods of measuring femoral anteversion. These methods use a strict geometrical definition of anteversion. The computerized tomography method of measuring anteversion that was developed recently, and is now widely used, does not adhere to the accepted definition of anteversion and has not been tested for accuracy in a large series. In the present study, the widely used computerized-tomography method of measuring anteversion was tested on thirty-two femoral specimens. With that method, anteversion was consistently underestimated by an average of 10 degrees compared with direct measurements and was reproducible only to within +/- 3.6 degrees. Therefore, a new method of measuring anteversion using computerized tomography was developed. It was shown to be accurate to +/- 1 degree, as tested on the same specimens. This study demonstrated geometrically why the currently practiced computerized-tomography method of selecting the points that are used to define the axis of the femoral neck is not consistent with geometrical definitions of anteversion. A more accurate method for both defining the axis of the femoral neck and measuring femoral anteversion is described and recommended for clinical use.

Cadaver↗

PubMed1986

Myoelectric analysis of the paraspinal musculature in relation to automobile driving.

In this study, the myoelectric activity of 12 paraspinal muscles of ten men aged 18-24 was recorded to examine the effects of backrest inclination and lumbar support in relation to driving. In total, 24 test conditions were evaluated over a 3.5-hour period in a single day. These tests were then repeated, changing the sequence over the next 4 days. The results indicate a complex interaction between the thoracic and lumbar regions of the back with the lowest myoelectric activity position of 120 degrees backrest inclination, 5 cm of lumbar support, and 13.5-18.5 degrees of seat inclination. Electromyogramatic (EMG) evidence of fatigue was not identified over a 3.5-hour period. The generally low levels of EMG activity and, presumably, disc pressure present in any seating position suggest that the paraspinal muscle activity may not play the predominant role in disc herniation as it relates to automobile driving.

Adolescent↗

PubMed1986

Computer-aided simulation, analysis, and design in orthopedic surgery.

Three-dimensional computer reconstructions of bony anatomy based on computed tomographic images and radiographs may be used to analyze, simulate, and design certain orthopedic procedures. In osteotomy surgery, the computer-reconstructed models may be used to measure critical angles, surface area, and congruity of the joint surfaces. Computer reconstructions may be used in total joint replacement surgery to simulate the effect of surgical reamers and rasps, to select the geometrically optimum standard implant, or to design a custom implant. In allograft reconstructive surgery, computer reconstructions may be used to measure bony defects and to identify the appropriate allografts for the reconstruction. Plastic models may be sterilized and used as templates to sculpt the allografts immediately preoperatively. In all three applications in orthopedic surgery, three-dimensional, computer-aided reconstructions have the potential to improve results and reduce morbidity.

Bone Transplantation↗

PubMed1986

A biomechanical analysis of racewalking gait.

The purpose of this study was to investigate the kinetic and kinematic properties of the lower extremity during the phases of the racewalking gait as defined by the rules and compare these to normal walking and running. Cinematographic and force plate data were gathered from 10 competitive racewalkers under four gait conditions. Temporal parameters, angular displacements of the lower extremity, ground reaction forces, path of the center of pressure, and the joint forces during the four gait conditions were compared using a repeated measures analysis of variance. Racewalkers exhibited significantly increased (P less than 0.01) maximal ankle dorsiflexion, maximal knee extension, angular displacements of the pelvis, medial ground-foot reaction forces, peak plantar flexion moment, and external peak knee hyperextension moment than did walking or running. Based upon the results of this investigation, it was determined that the gait of racewalking exhibits some biomechanical characteristics which are different from the gaits of walking or running.

Ankle Joint↗

PubMed1985

Spectroscopic studies of protein-heme interactions accompanying the allosteric transition in methemoglobins.

Resonance Raman, optical absorption, and circular dichroism spectroscopic techniques have been used to examine the effect of the addition of inositol hexaphosphate (IHP) to a series of carp and human methemoglobin derivatives. Markers of spin equilibrium in the high-frequency region (1450-1650 cm-1) of the resonance Raman spectrum yield high/low-spin ratios consistent with direct magnetic susceptibility measurements. Changes in the low-frequency region (100-600 cm-1) of the resonance Raman spectrum appear to correlate with the quaternary structure transition. Changes in the ultraviolet absorption spectra and the circular dichroism spectra also appear to be related to the quaternary structure change. By using the resonance Raman spin markers, we find that those derivatives of carp methemoglobin which are in spin equilibrium have a larger ratio of high-spin to low-spin populations than the corresponding derivatives of human methemoglobin. Upon the addition of IHP to the methemoglobins the spin equilibrium is shifted toward a larger high-spin population. This change in equilibrium is larger for the carp protein than for the human protein. We obtain an IHP-induced change in the free energy difference between the high-spin and low-spin states of 300 cal/mol for those human methemoglobins in which a quaternary structure change occurs and 600 cal/mol for carp methemoglobins. Our data are consistent with a quaternary structure change induced by IHP in all the carp methemoglobins studied (F-, H2O, SCN-, NO2-, N3-, and CN-) and in the F-, H2O, and SCN- derivatives of the human protein but not in the NO2-, N3-, and CN- derivatives. The Fe-CN stretching mode has been identified by isotopic substitution and found to be unchanged in frequency in carp CN- metHb when the quaternary structure is changed. On the basis of our results we conclude that the protein forces at the heme due to the addition of IHP do not significantly affect the position of the iron atom with respect to the heme plane. Rather, the changes in spin equilibrium may be caused by protein-induced changes in the orientation of the proximal histidine or tertiary structure changes in the heme pocket which affect the porphyrin macrocycle. Either of these changes, or a combination thereof, leads to changes in the iron d orbital energies and concomitant changes in the spin equilibrium.

Allosteric Regulation↗

PubMed1985

Picosecond time-resolved resonance Raman studies of hemoglobin: implications for reactivity.

Picosecond time-resolved Raman spectra of hemoglobin generated with blue pulses (20 to 30 picoseconds) that were resonant with the Soret band and of sufficient intensity to completely photodissociate the starting liganded sample are reported. For both R- and T-state liganded hemoglobins, the peak frequencies in the spectrum of the deoxy transient were the same at approximately 25 picoseconds as those observed at 10 nanoseconds subsequent to photodissociation. In particular, the large R-T differences in the frequency of the stretching mode for the iron-proximal histidine bond (VFe-His) detected in previously reported nanosecond-resolved spectra were also evident in the picosecond-resolved spectra. The implications of this finding with respect to the distribution of strain energy in the liganded protein and the origin of the time course for geminate recombination are discussed. On the basis of these results, a microscopic model is proposed in which delocalization of strain energy is strongly coupled to the coordinate of the iron. The model is used to explain the origin of the R-T differences in the rates of ligand dissociation.

Allosteric Regulation↗