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Biomedical subjects

R A Mendelson

Publications and source records attributed to R A Mendelson.

33 records · Page 2Linked to original sources
PubMed1981

EPR and fluorescence depolarization studies on bovine cardiac myosin.

To test for possible differences in local conformation and S1 flexibility, bovine cardiac and rabbit skeletal myosins were labeled with a fluorophore (1,5-IAEDANS) and a spin label having iodoacetamide reactivity. The marked activation of the Ca2+-ATPase (6- to 8-fold) and inhibition of the K+ (EDTA)-ATPase (80-90%) by both labels indicated specific labeling of the fast-reacting thiols (SH1) of both myosins. Fluorescence depolarization studies of 1,5-IAEDANS-labeled cardiac myosin indicated that, like skeletal myosin, the SI moieties of cardiac myosin exhibit considerable segmental flexibility with respect to the rod portion of the molecule. This indicates that segmental flexibility may be a property of all myosins. Cardiac and skeletal myosins immobilized spin labels to approximately the same extent, indicating a similarity in steric restraints around the SH1 thiol of the two myosins. The magnitude of the changes in spin label mobility accompanying binding of MgADP and hydrolysis of MgATP was reduced in cardiac myosin relative to skeletal myosin. This suggests that the lower catalytic center activity of cardiac myosin is associated with more restricted conformational changes accompanying formation of M.ADP and M.ADP.Pi. From measurements of spin label mobility, the affinity of cardiac and skeletal myosin for ADP were similar: Kd (ADP) = 7 microM, n = 1.6. The EPR spectrum of spin labels attached to cardiac and skeletal myosin showed similar saturation effects upon actin binding indicating immobilization of myosin heads occurs with both proteins.

Actins↗
PubMed1980

The effect of duration of alcohol administration on the deposition of trace elements in the fetal rat.

It is postulated that the effect of alcohol on trace element deposition during pregnancy is a long term one, requiring alcohol administration throughout the 21 days of gestation. Female Charles River rats (N = 30) were given a semi-synthetic diet throughout pregnancy. Half the animals received alcohol (8 ml/kg) by esophageal tube, the other half were sham operated. Within each group, animals were treated for one, two or three weeks beginning with day 0. Dams and pups were sacrificed following a natural delivery. Iron (Fe), copper (Cu), zinc (Zn), and magnesium (Mg) were measured in maternal and fetal tissues by atomic absorption spectrometry. The results indicated an increased fetal level of Zn, Mg, and Fe in all groups treated with alcohol. Increased fetal levels of Cu were found in the group treated for three weeks with alcohol. No differences were found in maternal tissue levels. These changes in fetal levels correspond to the effect of alcohol on gestation. Alcohol-treated litters were anywhere from 2 to 6 days overdue, providing a longer time period in utero for nutrient uptake.

Animals↗
PubMed1979

The effect of ethanol consumption on trace elements in the fetal rat.

It is postulated that in the fetus trace element alternations secondary to maternal alcohol ingestion contribute to fetal alcohol syndrome. Female Charles River CD rats were given a semi-synthetic diet through two pregnancies. Half of the animals received 6% ethanol (v/v) in their drinking water. The animals were divided into the following groups: Control group received the diet ad lib, alcohol group received the diet and alcohol ad lib, pair fed group received a diet isocaloric with the alcohol group, and the alcohol + ZnMg group received the basal diet with added magnesium, zinc and alcohol. On the twenty-first day of gestation animals were sacrificed and iron, copper, zinc and magnesium measured in maternal and fetal tissues by atomic absorption spectrophotometry. The results indicated significantly reduced fetal zinc in the alcohol group while copper and iron levels were increased. In maternal tissues, only the femur was affected. Zinc and magnesium were significantly reduced (p < 0.01) while iron was increased (p < 0.01). The observed effects were not due to reduced food intake. The expected changes in tissue zinc and magnesium were prevented by diets fortified with these minerals. These results are consistant with our hypothesis that alcohol interferes with trace element metabolism during pregnancy and that diet can be manipulated to alter its effects.

Alcohol Drinking↗
PubMed1978

Investigation of the shape and size of myosin subfragment 1 using small-angle X-ray scattering.

Measurement of x-ray scattering at very small angles by solutions of myosin subfragment 1 (S1) yields a radius of gyration of 3.24 nm (mean) +/- 0.03 nm (standard error for N = 9). If S1 is assumed to be ellipsoid of revolution, of uniform electron density, with a molecular weight of 1.15 X 10(5) and a partial specific volume of 0.73 cm3 g-1, then the axial ratio of the ellipsoid is 2.89 +/- 0.06 (prolate) or 0.26 +/- 0.01 (oblate), and the major axis is 13.0 +/- 0.2 nm (prolate) or 10.1 +/- 0.1 nm (oblate). Measurements at larger angles allow models of S1 morphology to be tested; theoretical scattering curves for various ellipsoids of revolution were calculated. The observed scatterina can be approximated by the scattering from ellipsoids with axial ratio 2.0 to 3.0 (prolate), or 0.25 to 0.4 (oblate). Models that fit the data over the range of scattering angles from 0 to 30 mrad are: prolate ellipsoid with axial ratio 2.3, major axis 12 nm; and oblate ellipsoid with axial ratio 0.4 and major axis 10 nm. Thus analyses of two parts of the scattering curve, by different methods, indicate that S1 is fae from spherical, and that its morphology may be approximated by ellipsoids of the aforesaid dimensions.

Models, Chemical↗
PubMed1976

Affinity of myosin S-1 for F-actin, measured by time-resolved fluorescence anisotropy.

The association constant for myosin subfragment-1 (S-1) and actin was measured, using a new application of fluorescence depolarization which capitalizes on the fact that S-1 has high rotational mobility while F-actin does not. Uncoupling of the time dependences of the anisotropy decay and the association/dissociation phenomena allowed the experimentally determined anisotropy decay curve to be fitted by a sum of two terms weighted by the mole fractions of the free and bound S-1. At 4 degrees C, ionic strength 0.16 M, and pH 7.0, the association constant Ka is (1.73 +/- 0.35) X 10(6) M-1 at infinite dilution. This makes the -deltaG degrees of binding of F-actin to S-1 similar to the -deltaG degrees of binding of ATP to S-1, and the possible physiological relevance of the similarity to muscle contraction is discussed.

Actins↗
PubMed1975

Electron paramagnetic resonance and nanosecond fluorescence depolarization studies on creatine-phosphokinase interaction with myosin and its fragments.

Recent reports in the literature have indicated a physical association of creatine-phosphokinase (CPK) with the tail portion of the myosin molecule. The present paper describes further studies on the interaction of CPK with myosin and myosin fragments, using the techniques of electron paramagnetic resonance (EPR) and nanosecond fluorescence depolarization. From EPR work, spin-labeled CPK appears to interact with myosin, tail-less myosin (heavy meromyosin [HMM]), and myosin heads (subfragment-1 [S1]), the extent of interaction being proportional to the S1 content of myosin or its fragments. Spin-labeled CPK did not evidence interaction with the headless myosin "rods," with myosin tails (light meromyosin [LMM]), with S2 necks (which connect S1 to the rest of the myosin molecule), or with actin. When a fluorescent dye is directed to the essential epsilon-amino group of CPK, nanosecond fluorescence depolarization studies indicate a substantial interaction with myosin, HMM, and S1, but very little with F-actin. When the "fast-reacting" thiol of the S1 moiety or the "essential thiol" of CPK was labeled with either a fluorescent dye or a spin label, no interaction between CPK and myosin (or S1) was detected.

Actins↗
PubMed1974

Use of fluorescence polarization to observe changes in attitude of S-1 moieties in muscle fibers.

The fluorophore, N(iodoacetylamino)-1-naphthylamine-5-sulfonic acid (1,5-IAEDANS), incubated with glycerinated psoas fibers primarily labels the S-1 moieties of such fibers, but it does not impair fiber contractility even when the degree of labeling is as high as 0.8 moles fluorophore per mole myosin. The polarization of the on-axis fluorescence from either the IAEDANS fluorophore, or the intrinsic tryptophane fluorophore, depends on whether the fiber is relaxed, in rigor, or developing isometric tension; furthermore, the changes in polarization on going from one state to another are much the same with either tryptophane or IAEDANS fluorophores. The foregoing is true whether the plane of the exciting light is parallel or perpendicular to the fiber axis. Also, if a fiber is first freed of its myosin by extraction, and is then incubated with IAEDANS-labeled S-1 the resulting polarization approaches that observed with a labeled, unextracted fiber in rigor. By contrast, incubation with the fluorophore, 7-nitro-4-chlorobenz-2-oxa-1,3-diazole (NBD-Cl) confers fluorescence only on actin, without impairing contractility, but the polarization of such fluorescence changes in a different direction and magnitude from myosin-originating fluorescence. It is concluded from these various observations that whether the fluorophore is IAEDANS or tryptophane the polarization change with change in physiological state originates in the S-1 moieties of fibers, and relates to the space attitude of these moieties.

Acetamides↗
PubMed1974

The site of force generation in muscle contraction as deduced from fluorescence polarization studies.

The fluorescent dye, N(-iodoacetylamino)-l-naphthylanine-5-sulfonic acid, labeled exclusively the myosin cross-bridges in rabbit glycerinated psoas muscle fibers, without impairing their function. Fluorescence polarization was used to study cross-bridge orientation in rigor, relaxation, and contraction, as a function of sarcomere length. At a length where no overlap between thick and thin filaments occurs, rigor-inducing, relaxation-inducing, and contraction-inducing solutions all induced the relaxation attitude. At lengths where overlap does exist, the slowly-hydrolyzing ATP analog, "alpha,beta-methylene ATP," induced the relaxation attitude. The data were consistent with the A. F. Huxley-Simmons model of force generation. Combined with our earlier results, the data indicated that torque was generated at the actin-myosin interface.

Animals↗
PubMedDate not supplied

Evaluating the accuracy of nutritional assessment techniques applied to hospitalized patients: methodology and comparisons.

Herein we describe a methodology which can be used to evaluate the predictive accuracy of nutritional assessment techniques. We use this methodology to compare seven techniques of nutritional assessment in terms of their ability to predict one nutrition associated hospital complication (infection) by dividing a sample of 59 surgical patients into high risk and low risk groups. One technique was subjective global assessment (SGA) of the patient's nutritional status on admission to hospital. Five techniques were single objective measurements (albumin, transferrin, delayed cutaneous hypersensitivity, anthropometry, and creatinine-height index). The 7th technique was the prognostic nutritional index. The best combination of sensitivity (0.82) and specificity (0.72) was found with SGA. The second best combination (0.88 and 0.45) was found by using either the prognostic nutritional index or creatinine-height index. We also found that combining the five objective measurements with SGA into a single index did not increase the discriminatory (or predictive) power over that of SGA alone in a clinically significant way. We conclude that a larger study comparing these approaches should be undertaken to confirm these findings and to develop methods which improve the predictive properties of SGA.

Anthropometry↗
PubMedDate not supplied

The choice to treat all, some, or no patients undergoing gastrointestinal surgery with nutritional support: a decision analysis approach.

We used decision analysis to compare three strategies for reducing the incidence of nutrition-associated complications in patients undergoing gastrointestinal surgery: treat all patients with nutritional support, treat no patients, or perform a test which categorizes patients as high or low risk (treating only the high risk patients). We use the model to make management recommendations based on current knowledge and to set priorities for future research. The "test strategy" is optimal in the majority of cases which we believe are clinically encountered when the test involves subjective global assessment of nutritional status on admission (sensitivity 0.82, specificity 0.72) and nutritional support must be delivered by a central venous catheter. However, the result is particularly sensitive to the predictive properties associated with the test and is less sensitive to the effectiveness rate of nutritional support in reducing the incidence of postoperative complications. We conclude that in future research priority should be given to studying and improving the predictive properties of nutritional assessment techniques.

Decision Making↗
PubMedDate not supplied

What is subjective global assessment of nutritional status?

Presented and described in detail is a clinical technique called subjective global assessment (SGA), which assesses nutritional status based on features of the history and physical examination. Illustrative cases are presented. To clarify further the nature of the SGA, the method was applied before gastrointestinal surgery to 202 hospitalized patients. The primary aim of the study was to determine the extent to which our clinician's SGA ratings were influenced by the individual clinical variables on which the clinicians were taught to base their assessments. Virtually all of these variables were significantly related to SGA class. Multivariate analysis showed that ratings were most affected by loss of subcutaneous tissue, muscle wasting, and weight loss. A high degree of interobserver agreement was found (kappa = 0.78, 95% confidence interval 0.624 to 0.944, p less than 0.001). We conclude that SGA can easily be taught to a variety of clinicians (residents, nurses), and that this technique is reproducible.

Humans↗
PubMedDate not supplied

Predicting nutrition-associated complications for patients undergoing gastrointestinal surgery.

We studied 202 patients admitted to two major teaching hospitals for planned gastrointestinal surgery to assess the ability of several techniques of nutritional assessment to predict major postoperative complications (infection and/or wound problems). Subjective global assessment (SGA) and albumin were both of predictive value, and combinations of these variables were useful in differentiating low-risk from high-risk patients. Transferrin, creatinine-height index, percent ideal weight, percent body fat, and total lymphocyte count were not useful in predicting complications. We conclude that SGA and albumin are useful "nutritional assessment techniques" for patients undergoing major gastrointestinal surgery if the purpose of such an assessment is to predict postoperative "nutrition-associated complications." The second major finding of this study was the unexpectedly low rate of complications (10%) which was found in both hospitals. We suggest that these low complication rates may be more generalizable to patient populations derived from a wide community base, rather than those described in other studies in which veterans or patients of lower socioeconomic status comprised the sample.

Female↗