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Biomedical subjects

M Sjöström

Publications and source records attributed to M Sjöström.

At least 19 recordsLinked to original sources
PubMed1999

Different sequence patterns in signal peptides from mycoplasmas, other gram-positive bacteria, and Escherichia coli: a multivariate data analysis.

Signal peptides are essential N-terminal extensions in export proteins, and have a positively charged N-terminus, a hydrophobic central core, and a C-terminal cleavage region. They interact in a consecutive manner with different accessory proteins during the secretion process. Potential patterns or periodicity in the amino acid (aa) sequence were searched, using multivariate techniques, for a large number of signal peptides from mollicutes (mycoplasmas), other Gram-positive bacteria, and Escherichia coli. Mollicutes signal peptides were significantly different from the E. coli and Gram-positive ones by their N-terminal charge, peptide length, and especially, unique periodicities of side chain hydrophobicity and volumes. Their lipoprotein signal peptides were longer than for any other bacteria. Significant differences were also recorded between the other bacterial peptide groups. Specific aa patterns were more related within the signal peptides from several groups of secreted bacillus enzymes, than for all signal peptides from one bacillus species. In E. coli, signal peptides from proteins routed for the various destinations revealed significant and compartment-specific sequence patterns not evident by other methods. This was substantiated from a large number of signal peptide secretion mutants for the E. coli periplasmic space. It is proposed that the differences in aa patterns and side-chain properties are related to the secondary structure sidedness and topology of the signal peptides, and important for specific interactions during the secretion process.

Amino Acid Sequence↗
PubMed1999

Inhibition of binding of an enzymatically stable thrombin inhibitor to lumenal proteases as an additional mechanism of intestinal absorption enhancement.

PURPOSE: The objective of the study was to investigate the mechanisms behind increased bioavailability of an enzymatically stable thrombin inhibitor, inogatran, after coadministration with a trypsin inhibitor, aprotinin. METHODS: Rat jejunum, ileum and colon segments were stripped and mounted in modified Ussing chambers, and the permeability to inogatran was determined both in the presence and absence of aprotinin. Inogatran and aprotinin were also coadministered intraduodenally to conscious rats. Competitive binding of inogatran to trypsin was studied using kinetic dialysis and was compared to aprotinin. The fraction of free (unbound) trypsin probe, in the absence of trypsin inhibitors was determined by performing experiments without pancreatine and without inhibitors, respectively. RESULTS: A 3-fold increased permeability to inogatran in the presence of aprotinin was seen in vitro, in some cases correlated with changed barrier properties of the intestinal segments. The in vitro results were well correlated with the in vivo results. There was a 5-fold increase in the bioavailability of inogatran in the presence of aprotinin. The binding of a trypsin probe was inhibited by both the presence of inogatran and aprotinin. Aprotinin showed a several fold higher displacement than inogatran. The results indicate both an effect of aprotinin on the epithelial membrane and an inhibition of binding of the thrombin inhibitor to trypsin or other serine proteases in the gut. CONCLUSIONS: The coadministration of aprotinin with enzymatically stable peptides, like thrombin inhibitors, may improve their absorption after oral administration. This suggests a new additional mechanism for intestinal absorption enhancement of peptide drugs.

Administration, Oral↗
PubMed1999

Simultaneous or delayed placement of titanium implants in free autogenous iliac bone grafts. Histological analysis of the bone graft-titanium interface in 10 consecutive patients.

The aim of the present study was to histologically analyse the bone graft-titanium implant interface after six and twelve months of healing for a simultaneous approach and after six months for a delayed approach. For this purpose, screw-shaped c.p. titanium microimplants, 2 mm in diameter and 5 mm long, were placed and retrieved at different time intervals in ten consecutive patients with severely resorbed maxillae and treated with iliac cortico-cancellous bone grafts and titanium implants in a two-stage procedure. The histomorphometrical analyses of ground sections of the specimens showed a higher degree of bone-implant contact and more bone filling the implant threads in the delayed approach microimplants. This was probably due to the partly revascularized grafted bone in the delayed approach being able to respond to the surgical trauma, resulting in interfacial bone formation. It is concluded that the results from the present study favour the use of a delayed approach when using free autogenous bone grafts and titanium implants for reconstruction of the severely atrophied maxilla.

Alveolar Process↗
PubMed1998

New chemical descriptors relevant for the design of biologically active peptides. A multivariate characterization of 87 amino acids.

In this study 87 amino acids (AA.s) have been characterized by 26 physicochemical descriptor variables. These descriptor variables include experimentally determined retention values in seven thin-layer chromatography (TLC) systems, three nuclear magnetic resonance (NMR) shift variables, and 16 calculated variables, namely six semiempirical molecular orbital indices, total, polar, and nonpolar surface area, van der Waals volume of the side chain, log P, molecular weight, and four indicator variables describing hydrogen bond donor and acceptor properties, and side chain charge. In the present study, the data from a previous characterization of 55 AA.s from our laboratory have been extended with data for 32 additional AA.s and 14 new descriptor variables. The new 32 AA.s were selected to represent both intermediate and more extreme physicochemical properties, compared to the 20 coded AA.s. The new extended and updated principal property scales, the z-scales, were calculated and aligned to previously reported z(old)-scales. The appropriateness of the extended z-scales were validated by the use in quantitative sequence-activity modeling (QSAM) of 89 elastase substrate analogues and in a QSAM of 29 neurotensin analogues.

Amino Acids↗
PubMed1997

Characterization of calcium phosphates precipitated from simulated body fluid of different buffering capacities.

The purpose of this experiment was to study the properties of calcium phosphate precipitated from simulated body fluids (SBFs) with different buffering capacities. The Ca/P molar ratios of the precipitates were determined and the microstructure of a sintered precipitate was studied. The results indicate that the pH of the SBF increases during calcium phosphate precipitations, which affects the Ca/P molar ratios and chemical compositions of these precipitates. A precipitate with a Ca/P molar ratio close to the stoichiometric molar ratio of hydroxyapatite was obtained when the pH of the SBF was continuously adjusted to 7.26 during precipitation. This precipitate has a fine-grained and laminated microstructure after sintering at 1000 degrees C in air. It seems that SBF can be used as a tool to study apatite-like precipitation in vitro when the pH of the solution is carefully controlled.

Biocompatible Materials↗
PubMed1996

Modelling of the biological activity for a set of ceramic fibre materials: a QSAR study.

The objective was to develop quantitative structure-activity relationships (QSARs) for a set of nine ceramic raw materials. The samples were characterized by a chemical analysis (both X-ray fluorescence and neutron activation analysis) and the morphology was determined by electron microscopy in combination with automated image analysis. Further, the fibre samples were subjected to two biological activity assays, measuring cytotoxicity and hydroxyl radical production. To investigate the produced data structures, principal component analysis (PCA) and partial least squares (PLS) were applied together with rigorous validation techniques. Significant QSARs were found for both biological activity assays. The morphology of the fibres plays an important role for the cytotoxicity and their trace element background is related to the hydroxyl radical production.

Animals↗
PubMed1996

Interleukin (IL)-6 and IL-8 in children with febrile urinary tract infection and asymptomatic bacteriuria.

Urine and serum interleukin (IL)-6 and IL-8 responses were higher in children with febrile urinary tract infection (n = 61) than in those with asymptomatic bacteriuria (n = 39). By univariate analysis, cytokine levels were related to age, sex, reflux, renal scarring, urine leukocytes, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and bacterial properties (P fimbriae but not hemolysin). Multivariate modeling showed that urine IL-6 responses were higher in girls than boys, increased with age, and were positively associated with CRP, ESR, serum IL-6, and urine leukocyte counts. The urine IL-8 response was not influenced by age, but it was influenced by P fimbriae and was associated with ESR, CRP, urine leukocytes, and female sex. The results show that cytokine responses to urinary tract infection vary with the severity of infection and that cytokine activation is influenced by a variety of host and bacterial variables.

Bacteriuria↗
PubMed1994

Similar regulatory mechanisms despite differences in membrane lipid composition in Acholeplasma laidlawii strains A-EF22 and B-PG9. A multivariate data analysis.

Mycoplasmas are small, cell wall-deficient bacteria. The metabolic regulation of the lipid composition in the membrane of the species Acholeplasma laidlawii, strains A-EF22 and B-JU, is governed mainly by the balance between the potential formation of lamellar and nonlamellar phase structures. However, the regulatory features have not been consistently observed in the B-PG9 strain. A comparison has been performed between the membrane lipid composition for strains A-EF22 and B-PG9, simultaneously changing eight experimental conditions known to affect the regulation and packing properties of the A-EF22 lipids. Multiple regression and partial least-square discriminant analyses of many variables showed: (i) quantitative differences in membrane lipid and protein composition, and in membrane protein molecular masses of the two strains; (ii) different molar fractions of the major polar lipids monoglucosyldiacylglycerol (nonlamellar) and diglucosyldiacylglycerol (lamellar), which were caused by differences in lipid acyl chain length and unsaturation inherent in the strains and by the type of growth medium used; and (iii) similar regulatory mechanisms for changes in the lipid composition under most conditions, responding to the experimentally varied bilayer and nonbilayer properties of the lipid matrix. These regulatory principles are probably valid in other bacteria as well.

Acholeplasma laidlawii↗
PubMed1994

Influence of zinc and copper administration on metal disposition in rats with cadmium-metallothionein-induced nephrotoxicity.

Only a few studies have investigated the effects of the interaction between Cu, Zn, and Cd on the toxicity of Cd in vivo and the metabolism of these metals. The present study is concerned with these effects. Observations of the distribution of these metals in liver and renal cortex and of their excretion in urine were made. Sixty male Wistar rats were divided into 10 groups of six (a full factorial design complemented by a center point and a control group) and were administered Zn (0 or 25 mg/kg body mass), Cu (0 or 12.5 mg/kg), and CdMT (cadmium--metallothionein; 0.1 or 0.4 mg Cd/kg) by sc injection. The rats were given Zn and/or Cu 24 hr prior to the CdMT injection. The data were analyzed by linear multiple regression. After CdMT injection, the Cd retention level was markedly reduced in renal cortex and increased in liver by Cu pretreatment, while the urinary excretion of Cd was significantly lower in these rats. The levels of endogenous Zn in renal cortex and liver increased significantly in rats pretreated with Cu. The production of MT in liver and renal cortex was induced more efficiently by Cu than by Zn. The results obtained may be of importance in understanding the mechanism of CdMT toxicity and the potential influence of Zn and Cu on the chronic nephrotoxicity of cadmium.

Animals↗
PubMed1992

Differences in fiber number and fiber type proportion within fascicles. A quantitative morphological study of whole vastus lateralis muscle from childhood to old age.

Data are presented on the number of fibers and the proportion of different fiber types within fascicles of whole vastus lateralis muscles from 5 male children, 5 to 15 years of age, and compared with results from 25 male adults, middle aged and old individuals. The results verify a difference in the proportion of fibers with different properties within a fascicle. The proportion of type 2 (fast twitch) fibers on the border of fascicles is larger than the proportion internally: the children have (P less than 0.01) greater difference than the adults and the middle aged, whereas the old have (P less than 0.001) less difference than the other age groups. The mean number of fibers per fascicle increases (P less than 0.05) from childhood to adult age, and thereafter reduces (P less than 0.01). The results imply that fascicles continuously rearrange during the normal growth and development and the normal aging process. It is argued that the causes of the difference in fiber type proportions within fascicles are local factors in the muscle, secondary to the overall age related functional demands put on the fiber population.

Adolescent↗
PubMed1992

Growth and development of human muscle: a quantitative morphological study of whole vastus lateralis from childhood to adult age.

The mechanisms underlying the increase in volume of muscle tissue, and the functional development of muscle fibers from childhood through adolescence to adult age, have been studied. Cross sections of autopsied whole vastus lateralis muscle from 22 previously physically healthy males, 5 to 37 years of age, were prepared enzyme histochemically (myofibrillar ATPase) and examined morphometrically. The data obtained on muscle cross-sectional area, size, total number, and proportion of type 1 (slow-twitch) and type 2 (fast-twitch) fibers were analyzed using linear regression techniques. The results show that the increase in muscle cross-sectional area from childhood to adult age is caused by an increase in mean fiber size. This is accompanied by a functional development of the fiber population: the proportion of type 2 fibers increases significantly from the age of 5 (approx. 35%) to the age of 20 (approx. 50%), which, in the absence of any discernible effect on the total number of fibers, is most likely caused by a transformation of type 1 to type 2 fibers.

Adolescent↗
PubMed1992

A multivariate study of protective effects of Zn and Cu against nephrotoxicity induced by cadmium metallothionein in rats.

Factorial experimental design was used to study the protective effects of Zn and Cu on cadmium-metallothionein(CdMT)-induced nephrotoxicity in male Wistar rats. In the factorial design two levels of Zn (0 and 25 mg/kg body weight), two levels of Cu (0 and 12.5 mg/kg), and two levels of CdMT (0.1 and 0.4 mg of Cd/kg) were used as varied factors. The factorial design was complemented with a center point with all three variables at an intermediate setting, i.e., Zn at 12.5 mg/kg, Cu at 6.25 mg/kg, and CdMT at 0.25 mg Cd/kg. Each of the nine combinations of settings was administered to one of nine groups with six rats in each. Zn and Cu were injected sc 24 hr prior to the injection of CdMT. The concentrations of protein and Ca in urine and Ca in renal cortex were used as effects. The relationship between the experimental design settings and the effects were modeled with multiple regression. The multiple regression analysis revealed that for the high dose of CdMT (i) the enhanced values of protein in urine caused by CdMT injection could be more efficiently reduced by Zn than by Cu, and (ii) excessive Ca in urine and renal cortex could be more efficiently reduced by Cu than by Zn. No significant synergism or antagonism between Cu and Zn was found. These models can be used to estimate the dose levels of Zn and Cu which will reduce the toxic effects of CdMT. The treatment of 20.4 mg/kg Zn, for example, will reduce the effects of 0.4 mg Cd/kg as CdMT on protein in urine, and 2.8 mg/kg Cu will reduce the Ca in urine to the levels of those caused by 0.25 mg Cd/kg (no Zn and Cu). Similarly, the effect of 0.4 mg Cd/kg on Ca level in renal cortex can be reduced to that of 0.28 mg Cd/kg as CdMT by 7.98 mg Cu/kg, which is three times as efficient as Zn. The obtained results might be of importance in understanding the mechanism of cadmium toxicity and the potential risk to the health of the population exposed to cadmium occupationally or environmentally.

Animals↗
PubMed1991

Evidence of fibre hyperplasia in human skeletal muscles from healthy young men? A left-right comparison of the fibre number in whole anterior tibialis muscles.

Cross-sections (thickness 10 microns) of whole autopsied left and right anterior tibialis muscles of seven young previously healthy right-handed men (mean age 23 years, range 18-32 years) were prepared for light-microscope enzyme histochemistry. Muscle cross-sectional area and total number of fibres, mean fibre size (indirectly determined) and proportion of the different fibre types (type 1 and type 2 on basis of myofibrillar adenosine triphosphatase characteristics), in each muscle cross-section were determined. The analysis showed that the cross-sectional area of the left muscle was significantly larger (P less than 0.05), and the total number of fibres was significantly higher (P less than 0.05), than for the corresponding right muscle. There was no significant difference for the mean fibre size or the proportion of the two fibre types. The results imply that long-term asymmetrical low-level daily demands on muscles of the left and the right lower leg in right-handed individuals provide enough stimuli to induce an enlargement of the muscles on the left side, and that this enlargement is due to an increase in the number of muscle fibres (fibre hyperplasia). Calculations based on the data also explain why the underlying process of hyperplasia is difficult, or even impossible, to detect in standard muscle biopsies.

Adaptation, Physiological↗
PubMed1991

Multivariate study of enterobacteria and Pseudomonas in saliva of patients with acute leukemia.

The effect of antibacterial treatment on the prevalence of gram-negative rods (enterobacteria and Pseudomonas) in the mouths of patients with leukemia was studied. Of the patients' salivary samples, 45% contained gram-negative rods compared with 12% in a control group of healthy persons. The antibacterial resistance patterns of gram-negative rods from healthy persons were different from those of the hospitalized patients. No relationship was found between the amount of antibacterial treatment and presence of gram-negative rods. The gram-negative rods recovered from individual patients were usually not resistant to the antibacterial agents given to the patients in question. Only a few patients harbored the same clone of a gram-negative rod for a lengthy period. The resistance patterns of these clones of gram-negative rods were similar to those of gram-negative rods that were transient in the mouth. It was concluded that resistance to antibacterial agents is not a factor of major importance for the capacity of the gram-negative rods to become established in the mouths of hospitalized patients with leukemia.

Adolescent↗
PubMed1991

Cryoultramicrotomy of muscle: improved preservation and resolution of muscle ultrastructure using negatively stained ultrathin cryosections.

Ultrathin sections of rapidly frozen, briefly pre-treated muscle tissue are cut and thereafter are thawed and contrasted using a negative staining technique. The method has provided micrographs in which the in-vivo order in the muscle fibres has been preserved well enough to enable both a more complete interpretation of X-ray diffraction evidence from muscle, and also a gain of new ultrastructural information on aspects of myofibril and myofilament architecture in different types of fibre. Examples here are taken from chicken, rabbit and fish muscles and show both the M-band and the bridge region of the A-band in great detail. To enhance the detail in the original images, one-dimensional (1-D) and 2-D averaging techniques (lateral smearing and step averaging, respectively) are used. Although there is major shrinkage in section thickness to about one-third of its original value, demonstrated here for the first time is the fact that the characteristic A-band lattice planes are preserved in these sections in 3-D. This confirms the usefulness of cryosections not just for 1-D and 2-D image processing, but also for 3-D reconstruction. Thus, in combination with techniques of image processing, cryoultramicrotomy can give the muscle morphologist the detailed data that are needed to match the molecular biologists, biochemists and immunologists in the interpretation of their data about physiological and pathophysiological events in muscle fibres at the macromolecular level.

Animals↗
PubMed1991

Minimum analogue peptide sets (MAPS) for quantitative structure-activity relationships.

The information contents in previously published peptide sets was compared with smaller sets of peptides selected according to statistical designs. It was found that minimum analogue peptide sets (MAPS) constructed by factorial or fractional factorial designs in physiochemical properties contained substantial structure-activity information. Although five to six times smaller than the originally published peptide sets the MAPS resulted in QSAR models able to predict biological activity. The QSARs derived from a MAPS of nine dipeptides, and from a set of 58 dipeptides inhibiting angiotensin converting enzyme were compared and found to be of equal strength. Furthermore, for a set of bitter tasting dipeptides it was found that an incomplete MAPS of 10 dipeptides gave just as good a model as the model based on a set of 48 dipeptides. By comparison other non-designed sets of peptides gave QSARs with poor predictive power. It was also demonstrated how MAPS centered on a lead peptide can be constructed as to specifically explore the physiochemical and biological properties in the vicinity of the lead. It was concluded that small information-rich peptide sets MAPS can be constructed on the basis of statistical designs with principal properties of amino acids as design variables.

Amino Acid Sequence↗
PubMed1991

Multivariate analyses of cellular fatty acids and carbohydrates of 1:2:1 and 2:4:2 spirochetes.

Delimitation of small-sized spirochetes of the oral cavity can be difficult. The endoflagella pattern has long served as the main criterion for taxonomic distinction. For approved species, e.g. Treponema denticola, several endoflagella patterns are observed, which indicates that this criterion is inadequate. The present study with GC and GC-MS used fatty acids and carbohydrates of whole-cell methanolysates to distinguish 1:2:1 and 2:4:2 subgingival spirochetes. Thirteen fatty acids: C12:0, C13:0, C14:0, Ciso-14:0, C2-OH-14:0, C15:0, Cante-15:0, C16:0, Ciso-16:0, C16:1, C18:0, C18:1, and C18:2, and three carbohydrates: rhamnose, glucose, and glucosamine, were detected. The carbohydrate contents did not differ between the two groups. While 1:2:1 spirochetes contained Ciso-14:0 and Cante-15:0 acid, 2:4:2 spirochetes did not. Also multivariate analyses of quantitative fatty acid data distinguished between these groups.

Carbohydrates↗