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Biomedical subjects

L Backman

Publications and source records attributed to L Backman.

At least 109 records · Page 6Linked to original sources

Shape control in the human red cell.

When the human red cell consumes its ATP, the cell loses its discoid character in favour of a spiculated and eventually a spherical form. This discocyte-echinocyte transformation parallels both degradation of phosphatidylinositol 4,5-bisphosphate and phosphatidic acid but not dephosphorylation of cytoskeletal proteins. Dephosphorylation of both spectrin and band 3 lags behind metabolic crenation. Exogenous vanadate accelerates both shape changes and lipid dephosphorylation in a parallel manner during metabolic depletion. In contrast to its effect on lipids, vanadate reduces the rate of protein dephosphorylation. These observations strongly support a shape control mechanism in the red cell, based on phosphoinositide metabolism and compatible with a bilayer-couple model.

Adenosine Triphosphate↗

Effect of spectrin dimer on actin polymerization.

Spectrin dimer is shown to influence the polymerization behaviour of actin. The polymerization of both Mg2+- and Ca2+-actin is regulated by an enhancement in the rate of nucleation and a fragmentation of preformed actin filaments. In addition, spectrin decreases the critical concentration of Ca2+-actin but not that of Mg2+-actin. This suggests that the two types of actin may differ in their interaction with spectrin dimer probably due to the different conformations. Band 4.1 elevates the effects of spectrin under non-equilibrium conditions but its contribution is less at steady state.

Actins↗

Glucagon receptor of human liver. Studies of its molecular weight and binding properties, and its ability to activate hepatic adenylyl cyclase of non-obese and obese subjects.

The glucagon receptor and the adenylyl cyclase system of human liver membranes were studied in six non-obese and six obese subjects who had elevated insulin and plasma glucagon levels. Analysis of specific glucagon binding by the method of Scatchard demonstrated a linear (monocomponent) plot with a dissociation constant of 2-3 nM, and the binding at low hormone concentrations was sensitive to guanosine triphosphate (GTP). The molecular weight of the glucagon receptor was 63,000 D as determined by an affinity labeling procedure and sodium dodecyl sulfate gel electrophoresis. Affinity labeling of this structure was specific for glucagon and inhibited by GTP. Glucagon stimulated the production of cyclic adenosine monophosphate (cAMP) by human membranes with half-maximal activation elicited by 6 nM hormone. The human cyclase system required GTP to facilitate an optimal glucagon response. NaF (10 mM) also activated the cyclase system and produced the same magnitude of response as maximum glucagon activation. A comparison of the liver adenylyl cyclase system of non-obese and obese subjects was made using glucagon (5 nM and 1 microM) and NaF (10 mM). No significant differences in cAMP production were noted between the two groups, regardless of the agent used to activate the enzyme. These findings agree with the glucagon binding studies that showed similar amounts of binding activity in the membranes from the two groups. Also, there was no influence of either age or sex of the subjects on the adenylyl cyclase response. In conclusion, human liver membranes contain a glucagon receptor and an adenylyl cyclase system that correspond closely to the well-studied system in animal liver. This system in human obesity is not altered by the approximately twofold elevation in plasma glucagon that occurs in this metabolic disorder.

Adenylyl Cyclases↗

Stomach distension in extremely obese and in normal subjects.

The maximal tolerable distension of the stomach was measured with a balloon system in 16 extremely obese and 11 normal-weight subjects. The mean maximal tolerated volume was significantly greater in the obese group (1763 +/- 70 vs. 1000 +/- 67 ml). The volume at which a satiety-simulating sensation appeared was likewise greater in the obese group (850 +/- 74 vs. 541 +/- 44 ml). The intragastric pressure originating from the stomach wall as such presumably was similar in both groups. The greater capacity for gastric distension in extremely obese persons may be an etiologic factor in the development of obesity or an adaptation to the eating pattern.

Adult↗

Calmodulin binding to human spectrin.

Calmodulin is shown to interact with human spectrin dimer. The binding was highly calcium-dependent and observed in two different kinds of experiments. Firstly, affinity chromatography of calmodulin on a Sepharose 4B column with immobilized spectrin, and secondly, partition in aqueous two-phase polymer systems. In the column experiments stoichiometric amounts of calmodulin were retained on the spectrin-Sepharose column when micromolar concentrations of calcium were present. The calmodulin bound could be eluted with EGTA. The partition coefficient of calmodulin in an aqueous two-phase polymer system containing calcium was changed upon addition of spectrin, indicating an association between the two proteins. In the absence of calcium, spectrin did not cause any change in the partition behaviour of calmodulin, thus showing that the association requires calcium.

Animals↗

Simplex optimization in biochemistry: application of the method in two-phase partition.

Partition in aqueous two-phase systems should have great potentialities for studies of biological material. However, the general use of the method has probably been hindered by the difficulties in finding the composition of two-phase systems with desired qualities. Experimental design has proved to be of immense value for optimization in many different areas and should also be useful in selecting the best possible two-phase system. Therefore the simplex method has been applied to the search for the composition of an aqueous two-phase system in which the partition behavior of filamentous actin and human spectrin differ as much as possible.

Actins↗

Binding and molecular weight properties of the insulin receptor from omental and subcutaneous adipocytes in human obesity.

The insulin binding properties and the molecular weights of the insulin receptor and its insulin binding subunit were studied in omental and subcutaneous adipocytes prepared from obese- and normal-weight subjects. Insulin binding by such adipocytes was decreased in obesity when the binding activity was expressed per unit of cell surface area. No significant difference from the lean controls was evident, however, when binding was calculated on a per cell basis, indicating that the total receptor content of the cells from the obese subjects was not altered. In addition, the normal difference in the receptor binding affinities previously reported between omental and subcutaneous cells from lean individuals was unaffected by the obese condition. Studies of the molecular weight of the non-reduced insulin receptor in fat cell membranes prepared from pieces of omental and subcutaneous fat demonstrated a major receptor species of 390-425K Mr. In contrast, adipocytes isolated by collagenase treatment of the fat had heterogeneous non-reduced receptor species of Mr 355K, 285K and small amounts of 427K and 182K. Although different non-reduced receptor species were evident depending on the adipocyte receptor preparation (e.g. isolated adipocytes or fat cell membranes), no differences were found between obese and lean controls or between subcutaneous and omental receptors when the appropriate comparisons were made. Upon sulphydryl reduction, all receptor preparations had a major binding subunit of 125K Mr. In conclusion, obesity is characterized by a dilution of the insulin receptor over the adipocyte cell surface in the absence of a change in total cellular content of receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

The rate of polymerization of rabbit skeletal muscle actin is enhanced by polyethylene glycol.

The effect of polyethylene glycol on the kinetics of actin polymerization was determined by monitoring the enhancement in the fluorescence of pyrenyl-labelled actin. The polymerization of actin at 15 mM KCl was in addition followed by viscometry and light scattering. All three methods showed that the overall rate of polymerization of actin increased 3-4-fold when the concentration of polyethylene glycol was increased from 0 to 6% (ww-1). A further increase in polyethylene glycol concentration to 10% (ww-1) caused a relatively small contribution to the increase in the rate of polymerization. The enhancement of the overall rate of polymerization by polyethylene glycol was also reflected in a significant decrease in the lag time observed when the time course of polymerization was followed by viscometry and light scattering. The steady-state value of fluorescence enhancement and critical concentration of actin were also influenced by polyethylene glycol and the results showed that the extent of polymerization was increased by an increase in the concentration of polyethylene glycol in solution. The effect of polyethylene glycol on both rate and extent of polymerization persisted at physiological salt concentration (150 mM KCl, 2 mM MgCl2). Since the rate of elongation was affected only to a small extent by polyethylene glycol, we propose that its main effect is on nucleation.

Actins↗

Computerized tomography: a method to study cross-sectional muscle area in nutritional evaluation.

We have compared two ways of determining cross-sectional muscle area in patients undergoing total parenteral nutrition, namely, computerised tomography and anthropometric measurements. There was a poor correlation between the two methods of determining cross-sectional limb area. The cross-sectional area increased in all patients considered on clinical grounds to have improved during the course of treatment.

Journal Article↗

Triglyceride metabolism in human liver: studies on hepatic phosphatidic-acid phosphatase in obese and non-obese subjects.

According to current concepts, soluble phosphatidic-acid phosphatase, converting phosphatidic acid into a diglyceride, is a rate-limiting enzyme in the hepatic biosynthesis of triglycerides. The present paper is the first report on this enzyme in human liver. The enzyme activity was assayed in ammonium sulphate precipitates of cytosol obtained from human liver biopsies. The activity was stimulated by preincubation with alkaline phosphatase and inhibited by Mg-ATP, suggesting that phosphorylation-dephosphorylation may be of some importance for the expression of the activity of the enzyme. When assayed under optimal conditions, the activity obtained in liver biopsies from normal-weight gallstone patients averaged 12.8 +/- 2.0 nmol min-1 (mg protein)-1 (mean +/- SEM) (n = 17). The enzyme activity was slightly higher in liver biopsies from morbidly obese subjects 16.4 +/- 2.8 nmol min-1 (mg protein)-1 (n = 14). The difference between the two groups of subjects was probably in part sex-dependent and was not statistically significant. A similar small and insignificant difference between the two groups of subjects was found when the enzyme activity was assayed in the maximally stimulated state--i.e. after incubation with alkaline phosphate. These findings suggest that an increased capacity of the soluble phosphatidic-acid phosphatase is not of major importance for the increased triglyceride synthesis known to occur in obesity. Other factors (i.e. availability of substrate and cofactors) may be of greater importance.

Adult↗

The significance of gastric pouch size and emptying time for results of gastric surgery for massive obesity.

The volume of the upper gastric pouch, the function of the draining channel and the pouch emptying time were examined with standardized technique in 15 patients during and after gastric surgery for massive obesity. Postoperatively the upper pouch was found to increase in volume up to fourfold compared to the value obtained at operation. The patients with the best clinical results showed the greatest increase in pouch size, indicating a tendency to outlet stenosis. This change was evident also from longer pouch draining time in these patients. A method for securing permanently slow drainage of the upper pouch seems to be a major problem in gastric surgery for obesity.

Adult↗

Reduced intestinal permeability to low-molecular-weight polyethyleneglycols (PEG 400) in patients with jejunoileal bypass.

The intestinal permeation and 6-hour urinary recovery of small, multisized tracers, polyethyleneglycol 400 (PEG 400), was used to characterize gut permeability in nine patients after bypass surgery for morbid obesity and in ten healthy volunteers. In the patients, who also had hyperoxaluria, the urinary recovery of ingested PEG 400 was lower than in the healthy persons (10.9 and 24.7%). The patients also showed stronger intestinal exclusion of the larger polymers within the PEG 400.

Adult↗

Nutritional assessment and postoperative morbidity. A prospective study in 286 consecutive surgical patients.

286 consecutive surgical patients went through a nutritional assessment following admission to the hospital. Serum albumin (S-alb), serum transferrin (S-transf), triceps skinfold (TSF) and arm muscle circumference (AMC) were recorded. The frequency of pathological values of TSF and AMC varied greatly depending on the reference population used to set the standard. There was no correlation between TSF or AMC and postoperative morbidity. S-alb less than 36 g/l and S-transf less than 2.0 g/l were associated with a marked increase in postoperative morbidity (29.4% and 20.0% respectively as compared to 7.6% in all operated patients). Thus S-alb and S-transf seemed to be able to predict postoperative morbidity. However, this ability varied depending on the diagnosis. Age was another factor with a marked influence on postoperative morbidity. It is suggested that attempts to make nutritional interpretations from S-alb and S-transf take into account patient age and the diagnosis. TSF and AMC seem to be of less value.

Adult↗

Malignant stenosis of the esophagus treated with dilatation or intubation.

Patients with incurable carcinoma of the esophagus or the cardia have a miserable life, without being able to swallow and with a risk for pulmonary complications secondary to aspiration of secretion from the esophagus. All efforts should be made to give these patients relief from dysphagia. Our experience indicates that the quality of life may be dramatically improved after dilatation or intubation which restores the ability to swallow, thereby reducing the risk for pulmonary complications.

Aged↗

Initial (1-year) weight loss after gastric banding, gastroplasty or gastric bypass.

Inadequate weight loss after gastric stapling operations for extreme obesity was found in an earlier study to be mainly due to dilatation of the outlet from the upper gastric pouch or rupture of the staple line. To avoid such failure we performed gastric banding with a Marlex mesh as originally suggested by Wilkinson. One year after surgery the criterion for acceptable weight loss (Broca's body weight index less than 1.20) was attained significantly more often after gastric banding than after gastric bypass or gastroplasty.

Adult↗

Association of rabbit muscle glycolytic enzymes with filamentous actin. A counter-current distribution study at high ionic strength.

The association between purified glycolytic enzymes and filamentous actin from rabbit muscle has been studied by counter-current distribution. The co-distribution of a glycolytic enzyme and filamentous actin leads to a significant change in the counter-current distribution profile of the enzyme whereas that of actin is unaffected. The changes in the distribution profiles clearly demonstrated that all glycolytic enzymes studied, though to different extents, bind to filamentous actin. The aqueous two-phase system used for the studies contained dextran, poly(ethyleneglycol) and 150 millimolal potassium phosphate buffer, pH 7.0. Since the ionic strength of the two-phase system is determined mainly by the buffer, the glycolytic enzymes are evidently able to associate with filamentous actin, at least in the presence of neutral polymers, at ionic strengths comparable to or higher than those assumed to prevail in vivo.

Actins↗