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Biomedical subjects

B Lindman

Publications and source records attributed to B Lindman.

At least 19 recordsLinked to original sources

Modification of the lyotropic liquid crystalline microstructure of amphiphilic block copolymers in the presence of cosolvents.

This article reviews the results of recent investigations on the macroscopic (phase behavior) and microscopic (microstructure) aspects of the role of cosolvents on the self-assembly of amphiphilic copolymers. A comprehensive account of the systematic studies performed in ternary isothermal systems consisting of a representative poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) block copolymer (Pluronic P105, EO37PO58EO37), water and a polar cosolvent (such as glycerol, propylene glycol or ethanol) is presented. The effect of cosolvents on the copolymer phase behavior is quantified in terms of the highest cosolvent/water ratio able to maintain the liquid crystalline structures. The effect of cosolvents on the microstructure of the lyotropic liquid crystals is quantified in terms of the degree of relative swelling per cosolvent content per copolymer content, a parameter that characterizes the given cosolvent and copolymer. The set of correlations on the cosolvent effects on the phase behavior or microstructure to the cosolvent physicochemical characteristics (such as octanol/water partition coefficient or solubility parameter) have led to the development of a hypothesis that accounts for the cosolvent effects on the self-assembly of PEO-PPO-PEO block copolymers and can be used to predict them. The rich structural diversity and the potential for a precise an convenient modification of the lyotropic liquid crystalline microstructure of the PEO-PPO-PEO block copolymers is discussed in comparison to the phase behavior of the low-molecular nonionic surfactants.

Journal Article↗

Sodium polyacrylate potentiates the anti-adhesion effect of a cellulose-derived polymer.

Available methods for postoperative adhesion prevention are insufficient. A previous study demonstrated that LM-200, a bioadhesive cellulose derivative was effective in reducing adhesions. Increasing the viscosity of a polymer solution enhances the tissue separating properties. Theoretically, a combination of sodium polyacrylate (PA) and LM-200 would give more viscous solutions than LM-200 alone, and thus be more efficacious. Therefore the efficacy of various combinations of LM-200 and PA was investigated. A lesion was created in the peritoneum of mice. The solutions to be tested, or saline, were given intraperitoneally. One week post-operatively, adhesion formation was quantified and expressed as a percentage of the original lesion covered with adhesions. PA (0.01 and 0.03 wt%) given separately did not differ in adhesion reducing effect from LM-200 (p = 0.3710 and 0.3481) but PA (0.1 wt%) resulted in significantly less adhesion formation (p = 0.0004). The effect of LM-200 increased significantly when adding PA (0.01 wt%) (p = 0.0007) or PA (0.03 wt%) (p < 0.0001). When adding PA (0.1 wt%) the effect was even more pronounced (p < 0.0001). The combination of a bioadhesive cellulose derivative and the polymer PA, was effective in reducing postoperative adhesion formation and a dose-dependent increase in efficacy was obtained compared to using the two components separately.

Abdomen↗

Prevention of adhesions by surfactants and cellulose derivatives in mice.

OBJECTIVE: To evaluate the efficacy of hydrophobically modified ethyl (hydroxyethyl) cellulose (cellulose), sodium hyaluronate (hyaluronate) and phosphatidylglycerol, in the reduction of adhesion formation. DESIGN: Controlled study. SETTING: Experimental academic unit, Sweden. MATERIAL: NMRI mice. Solutions: (1) cellulose, (2) hyaluronate, (3) phosphatidylglycerol, (4) phosphatidylglycerol and cellulose, and (5) phosphatidylglycerol, cellulose and hyaluronate. INTERVENTIONS: A standard lesion was created in the parietal peritoneum in mice. One of the viscous solutions to be tested, or saline, was given intraperitoneally. MAIN OUTCOME MEASURES: Amount of adhesions found one week postoperatively. RESULTS: Cellulose; phosphatidylglycerol and cellulose; and phosphatidylglycerol, cellulose and hyaluronate all significantly reduced the amount of adhesions (p=0.0002, p=0.002, p < 0.0001), as did the hyaluronate alone (p < 0.05). Phosphatidylglycerol alone did not reduce the amount of adhesions. Combining cellulose with phosphatidylglycerol, or with hyaluronate, did not improve efficacy. CONCLUSION: Cellulose and hyaluronate were effective in reducing the formation of adhesions. Combining cellulose with hyaluronate or phosphatidylglycerol or both did not improve efficacy.

Animals↗

Clinical significance of defective dendritic cell differentiation in cancer.

Defective dendritic cell (DC) function has been described previously in cancer patients and tumor-bearing mice. It can be an important factor in the escape of tumors from immune system control. However, the mechanism and clinical significance of this phenomenon remain unclear. Here, 93 patients with breast, head and neck, and lung cancer were investigated. The function of peripheral blood and tumor draining lymph node DCs was equally impaired in cancer patients, consistent with a systemic rather than a local effect of tumor on DCs. The number of DCs was dramatically reduced in the peripheral blood of cancer patients. This decrease was associated with the accumulation of cells lacking markers of mature hematopoietic cells. The presence of these immature cells was closely associated with the stage and duration of the disease. Surgical removal of tumor resulted in partial reversal of the observed effects. The presence of immature cells in the peripheral blood of cancer patients was closely associated with an increased plasma level of vascular endothelial growth factor but not interleukin 6, granulocyte macrophage colony-stimulating factor, macrophage colony-stimulating factor, interleukin 10, or transforming growth factor-beta and was decreased in lung cancer patients receiving therapy with antivascular endothelial growth factor antibodies. These data indicate that defective DC function in cancer patients is the result of decreased numbers of competent DCs and the accumulation of immature cells. This effect may have significant clinical implications.

Adult↗

DNA conformational dynamics in the presence of catanionic mixtures.

DNA conformational behavior in the presence of non-stoichiometric mixtures of two oppositely charged surfactants, cetyltrimethylammonium bromide and sodium octyl sulfate, was directly visualized in an aqueous solution with the use of a fluorescence microscopy technique. It was found that in the presence of cationic-rich catanionic mixtures, DNA molecules exhibit a conformational transition from elongated coil to compact globule states. Moreover, if the catanionic mixtures form positively charged vesicles, DNA is adsorbed onto the surface of the vesicles in a collapsed globular form. When anionic-rich catanionic mixtures are present in the solution, no change in the DNA conformational behavior was detected. Cryogenic transmission electron microscopy, as well as measurements of translational diffusion coefficients of individual DNA chains, supported our optical microscopy observations.

Anions↗

Polymers that reduce intraperitoneal adhesion formation.

BACKGROUND: Viscous macromolecules and phospholipids have been shown to reduce postoperative adhesion formation. The ideal agent, or combination of agents, still remains to be identified. METHODS: The effect of hydrophobically modified ethyl (hydroxyethyl) cellulose (HM-EHEC) and polyquarternium-24 (LM-200), two cellulose-derived polymers, and of sphingomyelin, was examined in an animal model. Adhesions were induced in the parietal peritoneum in a standardized manner and quantity, and the morphology of adhesion formation was evaluated after 7 days. RESULTS: A significant reduction in adhesion formation was seen in animals receiving LM-200 (P=0.013) and HM-EHEC (P=0.012) as a short-term treatment compared with controls given saline, but not in animals receiving sphingomyelin (P=0.733). Additional effects were seen in the animals receiving LM-200 as a prolonged treatment (P< 0.001) compared with controls. There was no difference in the magnitude of the inflammatory response between the groups. CONCLUSION: These results suggest that hydrophobically modified polymers are efficient in reducing adhesions, without affecting the inflammatory response.

Animals↗

Cytokine control of interstitial collagenase and collagenase-3 gene expression in human chondrocytes.

Human collagenase-3 expression, previously seen only in a breast tumor tissue, is here shown to be expressed in primary human chondrocytes derived from the joint tissue and in transformed human chondrocytes. Its mRNA is inducible by the inflammatory cytokines interleukin-1beta plus tumor necrosis factor-alpha, but not by phorbol 12-myristate 13-acetate and only slightly by the growth factors platelet-derived growth factor and epidermal growth factor. Human synovial fibroblasts, another prominent cell type in the joint tissue, do not produce collagenase-3 message. Expression of the murine collagenase, which is possibly the counterpart of human collagenase-3, is induced by interleukin-1beta plus tumor necrosis factor-alpha, and its full induction requires the presence of the transcription factor, c-FOS. This family of transcription factors also plays a role in induction of human collagenase-3, since it binds to the AP-1 site of this matrix metalloproteinase.

Animals↗

On the importance of hydroxyl groups in the polar head-group of nonionic surfactants and membrane lipids.

In this review properties of natural membrane lipids and surfactants synthesized from natural substances, such as paraffin chain alcohols and carbohydrates, are compared with those of synthetic surfactants of the polyoxyethylene type. Special attention is paid to the characteristic solution properties of nonionic surfactants with hydroxyl groups as the hydrophilic moiety, including alkyl glyceryl ethers and alkyl glucosides and maltosides, which are compared with those with oxyethylene groups. The major properties of the hydrophilic moiety are lipophobicity and hydrophilicity. Lipophobicity is an important property of oil-soluble surfactants, in particular for the polyoxyethylene alkyl ether type of surfactants where a too high lipophobicity may result in solubility in water.

Carbohydrate Sequence↗

Deuterium nuclear magnetic resonance studies on the interaction of glycophorin with 1,2-dimyristoylamido-1,2-deoxyphosphatidylcholine.

Membrane dynamics of dimyristoylphosphatidylcholine (DMPC) lipid bilayer which contains glycophorin with an artificial boundary lipid, 1,2-dimyristoylamido-1,2-deoxyphosphatidylcholine (DDPC), was investigated by 2H-NMR technique. For this purpose, both DMPC and DDPC were deuterated at the position of the 8th carbon atom of their acyl chains. Comparing, with DMPC bilayers, DDPC bilayers showed larger deuterium quadrupole splitting (delta nu rho) by approx. 2 kHz. This was explicable in terms of the stabilization of the membrane due to the formation of a strong hydrogen bonding in bilayers. Addition of glycophorin to the DMPC or DDPC single bilayers caused an increase in the delta nu rho value. The delta nu rho value of DMPC/DDPC mixed lipid bilayer was smaller than that of each single lipid bilayer DDPC in the DDPC/DMPC mixed bilayer was not phase-separated but homogeneously distributed. In glycophorin-reconstituted DMPC-d4/DDPC mixed bilayers, the delta nu rho of DMPC-d4 was almost identical to that of the simple DMPC-d4 bilayer. On the other hand, the delta nu rho of DDPC-d4 in the DMPC/DDPC-d4 mixed bilayer increased significantly upon the reconstitution of glycophorin. Judging from these data, we concluded that, in the DDPC/DMPC mixed bilayer which contains glycophorin, DMPC simply behaves as the matrix lipid, while DDPC surrounds glycophorin and certainly plays a role of the boundary lipid.

Chemical Phenomena↗

Heparin and heparan sulfate delimit nephron formation in fetal metanephric kidneys.

Formation of nephrons from primitive mesenchyme in fetal kidneys is induced by ureteric buds. Nephron induction is closely coordinated with branching morphogenesis of the ureteric bud. Having previously shown that branching of the primitive ureter is associated with de novo synthesis of chondroitin sulfate proteoglycan and release of free heparan sulfate glycosaminoglycan chains, we asked whether glycosaminoglycans influence nephron development. Fetal mouse kidneys were incubated in organ cultures containing heparan sulfate, heparin, chondroitin sulfate, or hyaluronate. After 48 hr the number of nephrons at each developmental stage was enumerated by light microscopic analysis of serial tissue sections. Kidneys incubated in heparin or in heparan sulfate contained up to 10-fold fewer nephrons than did kidneys incubated in control conditions or in chondroitin sulfate or hyaluronic acid. Maturation of nephrons, however, was unaffected. Inhibition of nephron development was associated with binding of labeled heparin to primitive mesenchyme and altered tissue distribution of fibronectin. Branching morphogenesis was impaired in kidneys exposed to heparin but not to heparan sulfate or to de-N-sulfated, N-acetylated heparin. The capacity of glycosaminoglycans to inhibit nephron formation depended on sugar composition and O-sulfation but not GAG chain size or charge density. Thus, heparan sulfate may have the capacity to specifically control formation of nephrons in fetal metanephric kidneys in vitro.

Animals↗

Vesicle formation in aqueous solutions of bile salt and monoacylglycerol.

We have investigated by means of quasielastic light scattering and freeze-fracture electron microscopy the aggregation behavior of aqueous solutions of taurocholate and monoolein. A spontaneous micelle-to-vesicle transition has been observed upon dilution of a mixed micellar solution. The size and stability of the micelles and vesicles present in these solutions has been studied as a function of the concentration and incubation time.

Freeze Fracturing↗

Coexistence of simple and mixed bile salt-lecithin micelles: an NMR self-diffusion study.

The aggregation behavior of bile salt and lecithin in aqueous solutions at 20 degrees C was studied from bile salt, lecithin, and aggregate self-diffusion coefficients obtained by means of a Fourier-transform NMR pulsed-gradient spin-echo technique. The results strongly support the coexistence of simple bile salt micelles and mixed bile salt-lecithin micelles under physiologic conditions.

Bile Acids and Salts↗

NMR studies on parvalbumin phylogeny and ionic interactions.

The inspection of several muscular parvalbumins from different species by two NMR methods (113Cd resonance and 1H relaxation measurements) allows two classes of parvalbumins to be distinguished according to their ion-binding properties. This result is in agreement with the phylogenetic classification of parvalbumins in two series, alpha and beta, which was established on the basis of the primary structures of these proteins. All parvalbumins are characterized by the presence of two primary cationic sites CD and EF, with structural features closely related to those already known on the basis of X-ray crystallographic studies of the beta parvalbumin pI 4.25 from carp muscle. However, parvalbumins of the beta series are characterized by a secondary cation (Ca2+, Mg2+ and other cations) binding site which is absent (or at least inaccessible) in parvalbumins of the alpha series. The major component from thornback ray (pI 4.45) behaves as an alpha parvalbumin as shown by the present NMR studies, although its primary structure suggests a closer similarity with the parvalbumins of the beta series.

Animals↗

Effect of NaCl on kinetics of D-glucosamine uptake in yeasts differing in halotolerance.

The initial rate of D-glucosamine uptake by the non-halotolerant yeast Saccharomyces cerevisiae was approximately halved as the apparent half saturation constant (Km) and the apparent maximum velocity (Vmax) changed from 6.6 mM to 16.4 mM and from 22 mumol.g-1.min-1 to 16 mumol.g-1.min-1, respectively, when the salinity in the medium was increased from zero M to 0.68 M NaCl. Corresponding changes in a high affinity transport system in the halotolerant yeast Debaryomyces hansenii were from 1.1 mM to 4.6 mM and from 3.1 mumol.g-1.min-1 to 4.5 mumol.g-1.min-1, implying a practically unchanged transport capacity. In 2.7 M NaCl, Km and Vmax in this system were 24.5 mM and 1.1 mumol.g-1.min-1, respectively, representing a marked decrease in transport capability. Nevertheless, the degree of affinity in this extreme salinity must still be regarded as noteworthy. In addition to the high affinity transport system in D. hansenii, a low affinity system, presumably without relevance in D-glucosamine transport, was observed.

Ascomycota↗

Magnesium and membrane function in vascular smooth muscle.

Since a tight electromechanical coupling exists in vascular smooth muscle, even small shifts of the membrane potential are sufficient to change the vascular lumen. The extracellular H+ and K+ concentrations are important effectors for the adjustment of the membrane potential. The ion concentrations in the immediate neighbourhood of the cell membrane can be influenced by the microdynamic binding properties of the basement membrane and the other vascular connective tissue. These structures are polyanionic macromolecules to which mono- and divalent cations are extensively bound, and which are separated from the vascular smooth muscle cell membranes by tiny cleft spaces. The ion binding properties of vascular connective tissue were therefore studied in dependence on proton and cation concentration. The pH-dependent binding of monovalent cations to vascular connective tissue is dependent on the concentration and affinity constant of the ion species in question. The mode of interaction is competition. For instance, the actual K binding characteristic means that an increase of [K+]o close to the cell membrane cold ensue from a diminished K+ binding ability under alkalosis. Depolarization and contraction of vascular smooth muscle cells result. Divalent cation binding to vascular connective tissue it additionally dependent on conformational changes. Already physiological concentrations of Mg++ ions can induce a specific change in configuration, which enables K+ ions to bind cooperatively. This means that with extracellular Mg++ deficiency not only less Mg++ ions are bound to vascular connective tissue but also less K+ ions. [K+]o would increase near the cell membrane, depolarization and vasoconstriction would occur.

Animals↗