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Biomedical subjects

B Sjöberg

Publications and source records attributed to B Sjöberg.

At least 37 records · Page 2Linked to original sources

Solution structure of human plasma fibronectin as a function of NaCl concentration determined by small-angle X-ray scattering.

The structure of human plasma fibronectin in 50 mM Tris-HCl buffer, pH 7.4, containing varying concentrations of NaCl, has been investigated using the small-angle X-ray method. Below 0.3 M NaCl the overall structure of the molecule is disc-shaped; at 0 M NaCl the axial ratio of the disc is about 1:7 and between 0.1 M to 0.3 M it is slightly more asymmetric, with an axial ratio of 1:10. At about 0.3 M NaCl there is a reversible transition to a more open structure, and, from 0.3 M up to 1.1 M NaCl the small-angle X-ray data can be explained by models consisting of ensembles of flexible, non-overlapping, bead-chains generated by a Monte Carlo procedure. Within this concentration range there is a gradual increase in the stiffness of the chains, as well as a decrease in bead radius, which indicates that the molecule becomes more open when the NaCl concentration is increased. The transition to a more open structure is also demonstrated by the average radius of gyration which increases gradually from 8.26 nm at 0 M NaCl to 8.75 nm at physiological or near-physiological conditions, and up to 16.2 nm at 1.1 M NaCl.

Fibronectins↗

Dodecylsulfate-induced dissociation of human alpha 2-macroglobulin. An investigation using small-angle neutron scattering and the equilibrium dialysis technique.

The dodecylsulfate-induced dissociation of the tetrameric alpha 2-macroglobulin molecule from human plasma has been investigated by the small-angle neutron scattering (SANS) method. The great advantage with the SANS method is that, by using deuterated dodecylsulfate, and contrast variation by changing the D2O/H2O ratio of the solvent, we can selectively study just the protein part, or the dodecylsulfate part, of the protein-dodecylsulfate complex. More than a thousandfold excess of dodecylsulfate (on a molar basis) is needed in order to dissociate alpha 2-macroglobulin to particles with, on average, half the original molecular mass. By combining the SANS data with results obtained by the equilibrium dialysis technique it follows that, under these circumstances, approximately one thousand dodecylsulfate molecules are associated per alpha 2-macroglobulin molecule. From the significant increase in the radius of gyration, which accompanies the dissociation process, we can conclude that the dissociation is associated with a drastic change in conformation of the protein molecule. From measurements where the dodecylsulfate part of the complex dominates the SANS signal we also get an indication that the dodecylsulfate is randomly distributed along the polypeptide chain, rather than being arranged in large clusters at certain regions of the protein molecule. By fitting the parameters of a binding model to the experimental data we obtain the result that most of the more than one thousand bound dodecylsulfate molecules, necessary for dissociation, are involved in the change in conformation, and the dissociation process is, in fact, driven by the binding of a very few extra dodecylsulfate molecules to the dissociation products. These data indicate that the dodecylsulfate-induced dissociation of alpha 2-macroglobulin is probably more complicated than just breaking, for instance, a hydrophobic interaction.

Dialysis↗

Solution structure of human plasma fibronectin using small-angle X-ray and neutron scattering at physiological pH and ionic strength.

Human plasma fibronectin has been investigated at physiological pH and ionic strength, by using small-angle X-ray and neutron scattering techniques. The results indicate that the molecule is disc shaped with an axial ratio of about 1:10. In fact, an ellipsoid of revolution with semiaxes a = 1.44 nm and b = c = 13.8 nm is in agreement with the experimental scattering data, and can also fully explain the rather extreme hydrodynamic parameters reported for fibronectin. The X-ray data gave a radius of gyration of 8.9 nm and a molecular weight of 510,000, whereas the neutron data gave slightly larger values, 9.5 nm and 530,000, respectively. From the volume of the best fitting ellipsoid we obtain a degree of hydration of 0.61 g H2O/g protein (dry weight). Neutron data, recorded at different D2O concentrations in the solvent, gave a match point of 43% D2O, which indicates that approximately 80% of the hydrogens bound to oxygen and nitrogen are exchangeable.

Fibronectins↗

Blood and tissue steroid levels and their interrelationship in men with pathological conditions of the reproductive organs.

We have investigated the interrelationship of the levels of 10 steroids in peripheral venous, spermatic arterial and spermatic venous blood, and in tissue specimens from the epididymis, vas deferens and testis from 8 patients who underwent orchidectomy for pathological conditions of the reproductive organs. The steroids analyzed by radioimmunoassay were: pregnenolone (5-P), dehydroepiandrosterone (DHEA), 17-hydroxyprogesterone (17-OH-P), androstenedione (A), testosterone (T), dihydrotestosterone (DHT) and the sulpho-conjugated forms (-S) of 5-P, DHEA, T and DHT. The quantitatively major steroids in peripheral venous blood were, in order of magnitude, DHEA-S, 5-P-S, DHT-S, T-S and T. No difference was observed between the levels of any of the steroids measured in peripheral venous and spermatic arterial blood. With the exception of DHEA-S and DHT-S, the levels of all steroids in spermatic venous blood were substantially higher than in peripheral venous blood (P less than 0.001). No correlation was found between steroid levels in spermatic venous and peripheral venous blood. Steroid concentrations in tissue from the epididymis, vas deferens and testis were markedly higher than in peripheral venous blood (P less than 0.01 to P less than 0.001), except for the levels of DHEA-S which were about equal in the various blood and tissue specimens. Tissue to blood ratios varied from approximately 2.0 to 500 according to the steroid in question. The peripheral blood levels of 5-P-S, DHEA-S and DHT-S were substantially higher than respective unconjugated steroid levels (P less than 0.001); the ratios (sulpho-conjugated to unconjugated) were approximately 17, 215 and 30, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Malate-aspartate and alpha-glycerophosphate shuttle enzyme levels in human skeletal muscle: methodological considerations and effect of endurance training.

The aim of the present study was to investigate whether the levels of the malate-aspartate and alpha-glycerophosphate shuttle enzymes in human skeletal muscle are affected by endurance training. The approach used was to compare six untrained and six endurance-trained subjects as well as through performing a longitudinal study of endurance training on eight untrained subjects. Biopsy samples were obtained from the lateral part of the quadriceps femoris muscle. The trained muscles were characterized by higher levels of oxidative enzymes (55%) as well as enhanced capillary supply (30%). In both the cross-sectional and longitudinal studies, the malate-aspartate shuttle enzyme levels were about 50% higher in the trained state (cytoplasmic malate dehydrogenase 36%, mitochondrial malate dehydrogenase 46%, cytoplasmic aspartate aminotransferase 52% and mitochondrial aspartate aminotransferase 48%). Contrary to this, the alpha-glycerophosphate shuttle enzyme levels did not differ significantly (cytoplasmic and mitochondrial glycerol-3-phosphate dehydrogenase: 10 and -4%, respectively). The activity ratios of the enzymes involved in respective shuttle did not differ significantly between the untrained and endurance-trained states. It is concluded that endurance training may induce increased levels of malate-aspartate shuttle enzymes in human skeletal muscle while the levels of the alpha-glycerophosphate shuttle enzymes are not affected. The study also includes results from several methodological experiments.

Adult↗

Outcome of different treatment modalities in cervix carcinoma Stage IB and IIA. Observations in a well-defined Swedish population.

Stage IB or IIA carcinoma of the cervix in a nonselected series of 263 young (less than or equal to 40 years) women was managed with radiotherapy alone or in combination with radical surgery. When the tumor was detected in Stage IB, the 5-year survival rate was 81% in the radiotherapy group and 96% in the combined therapy group. The corresponding figures for Stage IIA were 74% and 66%, respectively. When lymph node metastases were present at operation, the 5-year survival rate was reduced. The reduction was relatively small in Stage IB, but was decreased from 83% to 27% in Stage IIA. The size of the tumor had prognostic impact on the survival rate. Residual tumor in the surgical specimens was likewise associated with poorer prognosis in Stage IIA. The prediagnostic duration of symptoms indicates that the longer the pretreatment time and higher the stage at diagnosis, the greater the likelihood of metastatic spread. Adenocarcinomas comprised 13% of the tumors in the series. Complications of treatment were few.

Adenocarcinoma↗

Characterization of a half-molecular fragment obtained by reduction of human alpha 2-macroglobulin with dithiothreitol. A small-angle X-ray and neutron scattering investigation.

A half-molecular fragment of alpha 2-macroglobulin has been prepared by reducing and alkylating the inter-subunit disulfide bonds in the tetrameric alpha 2-macroglobulin molecule with 1 mM dithiothreitol (40 min) and 3 mM iodoacetamide (40 min). Further purification was made by gel chromatography and the homogeneous population of half-molecules has been characterized by the techniques of small-angle X-ray and neutron scattering. The radii of gyration found by the two methods are 57.0 and 58.0 A, respectively. The match point, obtained by neutron scattering from solutions with different H2O/D2O ratios, is at 43% D2O; the data are consistent with a particle having a higher scattering density at large distances from the particle centre. From the X-ray and neutron intensities scattered at zero angle, the specific volume was determined to be 0.73 cm3/g at +5 degrees C and the molecular weight to be 390,000; the latter value is associated with a relatively large error due to the uncertainty in the concentration determination. Shape analysis indicates that the best-fitting scattering-equivalent three-axial bodies are oblate shaped, with two of their axial dimensions about three to four times larger than the third one. From the volume of the best-fitting scattering-equivalent three-axial bodies, 0.72 X 10(6) A3, we obtain a water content equal to 0.38 g H2O/g protein (dry weight).

Dithiothreitol↗

Compatibility of parenteral nutrition solutions when mixed in a plastic bag.

The administration of a single admixture of the components used in total parenteral nutrition has been considered more convenient and to give rise to less infection than the conventional regimen with separate infusions. The physico- chemical properties of several admixtures corresponding to commonly used regimens for complete parenteral nutrition have been studied. A 28 day toxicity study was carried out in the dog for one of these mixtures. It was concluded that Intralipid an be mixed with Vamin and dextrose solutions, supplemented with electrolytes, trace elements and vitamins provided that the admixtures are within certain defined ranges, prepared under strictly aseptic conditions and used within a limited time. Deviations from these ranges and component formulae should not be made without appropriate testing.

Journal Article↗

Small-angle X-ray scattering study of the interaction between human alpha 2-macroglobulin and trypsin.

The interaction between human alpha 2-macroglobulin and trypsin yields a complex of two trypsin molecules and one alpha 2-macroglobulin molecule as the main product. This is indicated from small-angle X-ray titration measurements in 0.02 M Tris/HCl buffer of pH 7.40 containing 0.2 M NaCl and 5 mM EDTA. The radius of gyration for the complex was determined to be 7.1 nm. The complex formation coincides with a decrease in the first side maximum of the scattering curve for alpha 2-macroglobulin. A comparison of the experimental data with those calculated from various models indicates that the data are consistent with the scattering from a hollow cylinder containing two sites, each of which is partly filled with one trypsin molecule.

Humans↗

Hydrodynamics of micturition in stress-incontinent women. Comparisons of pressure and flow at different micturition volumes in stress-incontinent and continent women.

The urethral flow, resistance and closure pressure and bladder pressures in 19 stress-incontinent but otherwise healthy women were compared with the same parameters in 19 healthy, continent women. The micturition studies were performed at three predetermined levels of bladder filling. The urethral closure pressure, the premicturition intravesical pressure and detrusor pressure at micturition were significantly lower in the stress-incontinent women than in the continent group. The intravesical opening pressure showed no intergroup difference. The urethral and bladder pressure measurements in the incontinent women indicated musculo-elastic tissue with greater compliance and less contractility than in normal women.

Adult↗

Hydrodynamics of micturition following Marshall-Marchetti-Krantz procedure for stress urinary incontinence.

Nineteen stress-incontinent females have passed a urodynamic study before and six months after Marshall-Marchetti-Krantz (M-M-K) surgical procedure. It is concluded that postoperative changes in the urethral pressure profile are very limited. However, urethral closure pressure was elevated and functional length shortened, both probably statistically significantly. Synchronous pressure-flow studies pre- and post-operatively showed only slightly and not statistically significantly decreased peak-flow values for three different micturition volumes at detrusor micturitions. At straining micturitions peak-flow was significantly reduced. For small micturition volumes (200 ml) detrusor pressure at peak-flow and at maximum detrusor contraction was significantly elevated after surgery. Urethral resistance was significantly increased for 200 ml and 400 ml micturitions postoperatively, but at micturition with maximum bladder capacity no changes were found. If micturitions are made as detrusor micturitions without strain and with an adequate filling of the bladder, the changes found postoperatively hardly bear clinical significance. Micturitions with heavy straining postoperatively, however, give a reduced flow and increased residual urine to the extent that micturitions in this way should be avoided.

Adult↗

A study of the short-time variation and interrelationship of plasma hormone levels reflecting pituitary, adrenocortical and testicular function in fertile men.

Using radioimmunoassay method, we have estimated the levels of cortisol (C), pregnenolone (delta 5P), 17-hydroxypregnenolone (17-OH-delta 5P), dehydroepiandrosterone (DHEA), 17-hydroxyprogesterone (17-OH-P), androstenedione (A), testosterone (T) and dihydrotestosterone (DHT) in peripheral plasma samples collected at short-time (15 min) intervals from 10 fertile men, during two 4-h periods (06.00 to 10.00 and 18.00 to 22.00). In addition, the levels of biologically active luteinizing hormone (LH) were measured by an in vitro bioassay method in 9 of the subjects. The levels of all steroids studied exhibited diurnal variation with higher levels during the morning and lower levels during the evening period. The cortisol and the delta 5-steroid levels also exhibited individual short-term episodic spikes during the 2 periods. No short-term variation was observed in the levels of 17-OH-P, A, T and DHT. Statistically significant correlations were found between the levels of C and those of the delta 5-steroids and A in most of the subjects. No correlation was found between the above steroid levels and those of 17-OH-P, T and DHT. Also the LH levels exhibited episodic spikes of 60 to 90 min duration, but no diurnal variation. When the LH levels were related to those of T found in the same samples or in samples withdrawn 15 to 810 min afterwards, a significant positive correlation was found on repeated occasions in 5 of the 9 subjects. No systematic negative correlation was found when the T levels were related to those of LH in the same sequential fashion. Whereas the positive correlations found between LH and T levels in some of the subjects might suggest that physiological changes in peripheral LH levels are instrumental in regulating T-secretion, the rather consistent lack of significant negative correlation between T and LH levels seems to favour the view that the release of LH is not modulated by peripheral testosterone levels alone.

Adrenal Cortex Hormones↗

Diazepam adsorption to infusion sets and plastic syringes.

The adsorption of diazepam to infusion sets and plastic syringes was studied. Infusion solutions consisting of diazepam injection (Valium) in glucose 5.5%, or diazepam emulsion in a lipid emulsion (Intralipid 10%) were infused through two different infusion sets (Transcodan L-74 and Cutter IL). It was found that, when an infusion solution with a low diazepam concentration (0.04 mg/ml) was infused slowly (4 ml/h), the diazepam adsorption was more than 80%. At a higher diazepam concentration (0.1 mg/ml) and increased infusion rate (20ml/h) the adsorption decreased. Diazepam injection in glucose 5.5% was adsorbed to a higher degree (40-75%) than diazepam emulsion in glucose 5.5% (15-35%). When diazepam emulsion was diluted with the lipid emulsion, no diazepam adsorption to the infusion set occurred at this concentration and infusion rate. No significant difference between the two infusion sets could be found. The miscibility of diazepam emulsion with glucose 5.5%, glucose 10%, or sodium chloride 0.9% was examined. Diazepam emulsion proved to be miscible with glucose 5.5% and glucose 10%, but sodium chloride should not be used to dilute diazepam emulsion. The effect on the diazepam concentration of storing diazepam injection and diazepam emulsion in plastic syringes for up to 4h was also studied. It was found that the diazepam concentration remained unchanged during this time.

Adsorption↗

A small-angle X-ray scattering study of the complex formation between elongation factor Tu . GTP and valyl-tRNA Val I from Escherichia coli.

The complex formation between elongation factor Tu (EF-Tu) . GTP and valyl-tRNA Val 1 has been investigated using the small-angle X-ray scattering titration technique. The main species observed is a 1:1 complex with a stability constant log K greater than or equal to 6. The corresponding interaction between EF-Tu . GTP and non-aminoacylated tRNA appears to be much weaker with an estimated log K approximately equal to 4. The radius of gyration determined for the EF-Tu . GTP -- valyl-tRNA Val 1 complex is larger (R = 3.6 nm) than that of EF-Tu . GTP (R = 2.5 nm). Likewise, the maximum distance within this complex is larger (Dmax = 12.5 nm) than the one within EF-Tu . GTP (Dmax = 8.5 nm). These data as well as the p(r) curve are consistent with a multiellipsoid model for the complex. From this model it is indicated that the acceptor stem of tRNA is attached to EF-Tu and that the anticodon stem and loop protrude into the solution.

Bacterial Proteins↗

Hydrodynamics of micturition in healthy females: pressure and flow at different micturition volumes.

A new urodynamic technique, in which detrusor and bladder pressures are recorded with suprapubic percutaneous catheters, was used for investigation of 19 healthy female volunteers to obtain urodynamic reference values. The investigation was made in parous as well as in nulliparous women of varying ages. Apart from a significantly elevated premicturition pressure in the elderly women, neither age nor parity seemed to change urodynamic parameters. Voidings with three different, defined bladder volumes in each volunteer indicated that flow increased with a larger volume up to a certain limit (400 ml) but further increase of volume did not raise the flow. All total bladder pressures, maximum detrusor pressures, and detrusor pressures at maximum flow at micturitions were independent of bladder volumes. Micturitions were made as detrusor micturitions as all volunteers were requested not to strain at voiding. It is considered that detrusor micturitions must be the best way to obtain comparable parameters from different urodynamic investigations.

Adult↗

Clinical experiences of direct transmural measurement of the detrusor pressure.

The clinical value of a technique using suprapubic catheters prevesically and intravesically for detrusor pressure recordings is analysed. The method has been used in 143 investigations including both males and females. The complication rate is low, 2.8%, and the advantages of a well defined measuring level and identical measuring systems for all pressure recordings are stressed. It is also concluded that there seems to be no risk of infection. For repeated investigations, such as when, for instance a second postoperative urodynamic check is wanted, this technique does not involve any drawbacks due to surgical trauma. The technique with two suprapubic catheters is well accepted by the patients and is preferred to rectal catheters by volunteers who have tried both types.

Adult↗