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Biomedical subjects

S R Simon

Publications and source records attributed to S R Simon.

At least 91 records · Page 5Linked to original sources

Polymerized liposomes as stable oxygen-carriers.

We have produced a surrogate erythrocyte ('hemosomes') by encapsulating human hemoglobin in polymerized vesicles composed of diacetylenic phospholipids plus or minus cholesterol. Hemoglobin (in the presence or absence of allosteric effectors) was encapsulated by a freeze-thaw method in large, unilamellar vesicles composed of monomeric lipids. Entrapment was demonstrated by molecular-sieve chromatography. Brief irradiation with ultraviolet light produced polymeric hemosomes with polymerization kinetics and conversions similar to liposomes in the absence of protein. Photo-induced oxidation of the heme was eliminated or severely limited by a combination of prior ligation with CO and the maintenance of high intravesicular hemoglobin concentrations (5-10 mM internal hemoglobin). The inclusion of allosteric effectors within polymerized hemosomes facilitated near-quantitative conversion to the oxy-HbA form. Gas permeability of monomeric and polymeric hemosomes was demonstrated by spectroscopic methods. Reversible spectral shifts, corresponding to oxygenation-deoxygenation, were obtained after brief evacuation and exposure to oxygen or nitrogen. The gas permeability of polymerized hemosomes appears sufficient for the vesicles to act as oxygen carriers in vivo, a notion that is strengthened by their apparent hemocompatibility.

Blood Substitutes↗

Localized control of ligand binding in hemoglobin: effect of tertiary structure on picosecond geminate recombination.

The picosecond geminate rebinding of molecular oxygen was monitored in a variety of different human, reptilian, and fish hemoglobins. The fast (100 to 200 picoseconds) component of the rebinding is highly sensitive to protein structure. Both proximal and distal perturbations of the heme affect this rebinding process. The rebinding yield for the fast process correlates with the frequency of the stretching motion of the iron-proximal histidine mode (VFe-His) observed in the transient Raman spectra of photodissociated ligated hemoglobins. The high-affinity R-state species exhibit the highest values for VFe-His and the highest yields for fast rebinding, whereas low affinity R-state species and T-state species exhibit lower values of VFe-His and correspondingly reduced yields for this geminate process. These findings link protein control of ligand binding with events at the heme.

Animals↗

Horner's syndrome: an unusual presentation of Hodgkin's disease.

Horner's Syndrome (ptosis, anisocoria, and anhydrosis) developed in a 22-year-old woman. A mediastinal mass was noted on chest x-ray. Further evaluation led to a diagnosis of Hodgkin's disease, nodular sclerosis type. Horner's syndrome is an unusual initial manifestation of Hodgkin's disease, and, in this case, it was due to oculosympathetic damage from mediastinal compression. Because the potential for cure is high in Hodgkin's disease, this diagnosis should be considered in patients presenting with Horner's syndrome.

Adult↗

Modification of spastic gait through mechanical damping.

The effect of dissipative mechanical loads on spastic gait has been studied, to evaluate the feasibility of using mechanically damped orthoses to effect functional improvements in the gait of spastic patients. This concept is based on a hypothesis citing uninhibited, velocity-dependent stretch reflexes as a possible causal factor in spastic gait abnormalities, such as equinus and back-kneeing. In order to screen potential experimental subjects and to quantify velocity-dependent reflex behaviour, ankle rotation experiments and filmed gait analysis were performed. The results supported the existence of a velocity threshold. Orthosis simulation experiments were performed with one spastic subject, using a wearable, computer-controlled, electromechanical, below-knee orthosis simulator to apply a variety of damping loads to the ankle as the subject walked. Results indicated that appropriate damping can improve local joint kinematics. The damping causes a reduction in muscle stretch velocity which apparently results in reduced spastic reflex activity.

Adult↗

Elbow moment and forces at the hands during swing-through axillary crutch gait.

We investigated swing-through axillary crutch gait (nonweight bearing on the left lower extremity) to determine the effects of gait speed, crutch length, and handle position on the forces exerted at the hands and on the moments exerted about the elbow joints. Ten healthy subjects, skilled in swing-through crutch gait, walked at three speeds using fitted crutches, at a fixed speed with four different crutch lengths, and at a fixed speed with four different handle positions. We collected ground reaction forces that exerted simultaneously on the right crutch and motion data with a force plate and three high-speed movie cameras. A biomechanical model was developed to calculate the forces exerted at the right hand and the moments exerted about the right elbow joint. Changing gait speed from slow to the normal gait of the subject showed statistically significant effects (p less than .05) on the forces at the hand. When we changed crutch heights for the subjects, we found no significant effects on the forces at the subjects' hands. Changing handle position significantly affected the moment at the elbow. Increasing the elbow-flexion angle above 30 degrees by raising the crutch handle 1 to 2 in resulted in a 100 percent increase in elbow-extension moment. We found a correlation of .82 between actual average elbow-flexion angle and elbow-extension moment. Changing gait speed or crutch length did not affect elbow moment.

Adult↗

Biomechanical comparison of rising from two types of chairs.

This study compared the joint moments and ranges of motion of healthy subjects and patients during rising from a standard chair with a seat height of 0.43 m and a specially designed chair (E-Z Up Artherapedic Chair) with a seat height of 0.64 m. Ten healthy male subjects and four male patients with lower extremity disabilities rose from each chair with and without the use of their upper extremities. Hip, knee, and ankle joint moments and angles were calculated with film analysis and force plate data. An analysis of variance with repeated measures showed the following results for the healthy subjects: 1) no effect of upper extremity use on joint angles, 2) no effect of chair type on ankle joint angles or moments, 3) significantly smaller hip and knee flexion angles with use of the E-Z chair than of the standard chair (p less than .05), and 4) significantly smaller hip and knee extension moments with use of the E-Z chair than of the standard chair (p less than .05) or with use of the upper extremities. Similar results were found with the four disabled subjects. Use of the E-Z chair can significantly decrease the joint moments and ranges of motion needed at the hip and knee and thus make rising from a chair less stressful to these joints.

Adult↗

Free microvascular muscle flaps with skin graft reconstruction of extensive defects of the foot: a clinical and gait analysis study.

Over the past 4 years at the Massachusetts General Hospital 18 patients have been treated for extensive defects (mean size 130 cm2) of the foot at or below the medial and lateral malleoli. These patients have been treated with free muscle flaps covered with thick split-thickness skin grafts. Full muscle flap survival has been seen in each patient, and all patients are currently ambulatory. A subgroup of nine patients are weight-bearing directly upon their skin grafts covering transferred muscle. All patients are walking without chronic breakdown over a mean follow-up of over 19 months with the exception of a single patient who has had breakdown in a region of redundant improperly tailored muscle flap. None of the skin grafted muscles has significant cutaneous sensibility. Detailed gait analysis of these patients has confirmed the weight-bearing capabilities of free muscle flaps with skin grafts and has proven to be an excellent method of foot reconstruction evaluation. It would appear from this study that cutaneous sensibility may not be necessary for successful reconstruction of the weight-bearing surface of the foot. This method of reconstruction should be considered when local tissues are not suitable for plantar foot reconstruction.

Adolescent↗

Subcellular localization and further characterization of a new elastase inhibitor from pneumococci.

Streptococcus pneumoniae contains an inhibitor of human neutrophil elastase. The agent does not inhibit other proteases, including neutrophil cathepsin G and pancreatic elastase. It is active in the presence of insoluble elastin as well as synthetic elastase substrates. The inhibitor is present in the pneumococcal cell membrane. [125I]elastase binding studies and inhibition experiments with intact bacterial autoplasts suggest that this agent has its elastase-binding site(s) exposed on the outside of the bacterial cell membrane. Native and randomized membrane vesicles also show equal inhibitory activity. Active inhibitor can be solubilized from pneumococcal membranes by treatment with a dipolar ionic detergent and can then be reconstituted, in active form, within artificial liposomes. Complex formation between the neutrophil elastase inhibitor and neutrophil elastase may involve noncovalent associations. Although elastase containing a covalently bound substrate analog no longer binds the pneumococcal inhibitor, the present study shows that complex formation is nevertheless independent of neutrophil elastase catalytic activity. Specific inhibitor activity and inhibitor release during bile salt-stimulated autolysis are greater in a nonnecrotizing pneumococcal strain (type I) than they are in a necrotizing strain (type III) or in Klebsiella pneumoniae. These results may help explain the frequent resolution of some pneumococcal pneumonias, despite the presence in the early pneumonic exudate of many neutrophils containing an elastolytic protease capable of injuring lung connective tissue.

Autolysis↗

Hormonal influences on growth of B16 murine melanoma.

The influence of endocrine factors on B16 melanoma growth was investigated in young and old male mice to test the hypothesis that senescent hormonal changes account for the age-associated reduced tumor growth previously observed in our laboratory. Again it was demonstrated that tumors grow more slowly and to a lesser volume in old mice. For a test of whether senescent hormonal changes account for this tumor growth pattern, B16 was implanted into male and female C57BL/6 mice and tumor growth observed. In addition, young adult male mice were castrated and later B16 melanoma growth was determined. Tumor growth was similar in male and female mice. Contrary to our expectations, however, castrated male mice demonstrated larger tumor volumes, despite serum testosterone levels similar to those of old mice. Furthermore, after iv tumor cell injection, the occurrence of pulmonary colonies was greater in castrated mice. These observations indicate the importance of hormonal factors in this commonly explored tumor system. With regard to aging and tumor growth, however, senescent sex hormone changes probably do not account for the slower tumor growth observed in aged animals.

Age Factors↗

Postural adjustments associated with rapid voluntary arm movements 1. Electromyographic data.

Normal subjects made bilaterally symmetric rapid elbow flexions or extensions ("focal movement") while free standing or when supported by being strapped to a firm wall behind them (different "postural set"). In some trials a load opposed the movement two thirds of the way into its course. Electromyographic activity in leg and trunk muscles ("associated postural adjustments") demonstrated specific patterns for each type of movement. Activity in these muscles began prior to activity in the arm muscles and demonstrated a distal-to-proximal order of activation. The EMG patterns were characterised by alternating activity in the antagonist pairs similar to the triphasic pattern seen in the arm muscles. When the movement type was changed change of the pattern of the postural muscles occurred over several trials. It is concluded that the associated postural adjustments are pre-programmed motor activity linked to the focal movement, specific for the focal movement including anticipated events and the postural set.

Adult↗

Hemorrhagic diathesis in multiple myeloma.

Hemorrhage occurs during the clinical course in 15% of patients with multiple myeloma. We recently treated a patient with myeloma who had postoperative bleeding and hematuria despite normal coagulation parameters and platelet count. Platelet function studies revealed markedly abnormal aggregation to all stimulants. Plasma exchange successfully reversed in vitro and in vivo bleeding abnormalities.

Blood Platelet Disorders↗

Gait patterns in patients with amyotrophic lateral sclerosis.

A study of 24 patients with amyotrophic lateral sclerosis (ALS) was done to evaluate the relationship between the disease state and walking performance. Each was filmed with high speed cameras as he/she walked at free speed. Spatial position of points on the limbs were quantified from films with a digitizer and a computer. Velocity, cadence, stride length, timing parameters, and joint patterns of the lower extremity were calculated with these data. Both cadence and stride length were seen to decrease as velocity decreased. Patients spent less time on one leg (single limb stance) and more time on two legs during walking as velocity decreased. No relationship was found between walking parameters and pulmonary function, type of neurologic symptoms, or number of months since diagnosis. The clinical feature that correlated best with walking performance was lower extremity muscle strength. Stride length was decreased in the slower walkers by a decrease in hip excursion into flexion and extension, excessive knee flexion at initial contact, and diminished plantarflexion at weight release.

Adult↗

The development of gait: a study in African children ages one to five.

The purpose of this study was to describe quantitatively the gait development of a group of African children to determine how the pattern changes would relate to growth and maturation. This work applies an established technology of gait analysis to field conditions. 65 children of the Gusii tribe from southwestern Kenya were selected for study with an age range from 13 months to 69 months. Gait evaluation was performed by film recording free-cadence walking of the children. Growth in stature and age both influence the gait patterns. Developmental patterns of alteration in velocity, stride length, and cadence quantitatively measured in this study closely parallel observations made on children in laboratory settings by other workers.

Body Height↗

Danazol for the treatment of idiopathic thrombocytopenic purpura.

Idiopathic thrombocytopenic purpura is an autoimmune disorder, most common in young women. We treated 22 patients with this disorder (12 of whom were women) with danazol, an androgen with reduced virilizing capability, for two months or longer. Fifteen had undergone splenectomy, all were receiving glucocorticoids, and 18 had also been given other treatments. Fifteen of the patients were benefited, 11 with sustained normalization of their platelet counts. Six of eight patients tested had initial increases in circulating platelet-reactive IgG; in all six there was a marked decrease concomitant with danazol therapy. Danazol was effective in both men and women, irrespective of previous treatments. The duration of remissions ranged from 2 to 13 months. The drug was well tolerated and appears to be better suited than glucocorticoids for long-term management of idiopathic thrombocytopenic purpura, but the exact indications for the use of danazol in this disorder remain to be determined.

Adult↗

Resonance Raman spectra of photodissociated carbonmonoxy hemoglobin and deoxy hemoglobin at 10 K.

Resonance Raman data from deoxy hemoglobin and photodissociated carbonmonoxy hemoglobin (Hb*) at low temperature (10 K) are reported. At this temperature with 457.9 nm excitation, the iron-histidine (Fe-His) stretching mode in deoxy hemoglobin disappears, although with 441.6 nm excitation it is detected at 235 cm-1. The intensity change is interpreted as resulting from changes in energy of iron d orbitals induced by the shortening of the Fe-His bond on temperature reduction. The previously reported narrowing of the Fe-His mode with temperature reduction has been found to be artifact. In Hb*, the Fe-His stretching mode is present with 457.9 nm as well as 441.6 nm excitation and is at higher frequency (242-244 cm-1) than it is in the deoxy samples. Several porphyrin skeletal frequencies are also shifted in Hb* with respect to deoxy hemoglobin. These data are interpreted as resulting from perturbations on the ligand-free histidine-porphyrin complex by the liganded conformation of the heme pocket. We find no evidence that the dissociated CO molecule interacts with the heme in Hb*.

Carboxyhemoglobin↗

Comparison of mechanical work and metabolic energy consumption during normal gait.

The validity of using mechanical measures of work to indicate the metabolic energy consumption during normal gait was examined. These mechanical measures were (a) mechanical work done on the center of mass per kilogram body mass per second (Wcm), calculated by integration of ground reaction forces measured by force platforms; (b) total body segmental work per kilogram body mass per second (Wseg), calculated from individual body segment energies measured by motion analysis; and (c) the sum of the normalized absolute moment impulses per second acting on the joints of the lower extremities (M), calculated from both force and motion data. The metabolic energy consumption, determined by analysis of expired air, and the three mechanical measures of work were calculated for six normal subjects walking at five speeds. Each measure of mechanical work per second walked was highly correlated with metabolic energy consumption/kg X s (r = 0.89 for Wcm, r = 0.79 for Wseg, and r = 0.85 for M), but a poorer correlation was found between each measure of mechanical work per meter walked and net metabolic energy consumption/kg X m (r = 0.54 for Wcm, r = 0.28 for Wseg, and r = 0.03 for M). These mechanical parameters, particularly when measured per time, may be useful in comparing metabolic energy consumption between individuals or between different walking conditions for the same individual.

Adult↗

Stretch reflexes of triceps surae in patients with upper motor neuron syndromes.

Electromyographic responses of triceps surae to dorsiflexion stretch were studied in 47 patients with a variety of lesions producing an upper motor neuron syndrome. The short latency spinal reflexes, both when the patient was at rest and when he was exerting a voluntary plantarflexion, were frequently enhanced in magnitude and the rate of increase with acceleration was also enhanced. Long-latency reflexes were uncommon at rest. With background force long-latency reflexes were present unless the short latency reflex was very large. Long latency reflexes often were normal, but in some patients they were either excessively larger or even of abnormal shape with prolonged continuous activity. The clinical assessment of the ankle jerk correlated with the magnitude of the short latency reflex. The clinical assessment of tone correlated with the magnitude of the short latency reflex, the magnitude of the long latency reflex and the duration of the long latency reflex. There appear to be multiple physiological mechanisms underlying the clinical phenomenon of spasticity.

Cerebral Cortex↗