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J C Madsen

Publications and source records attributed to J C Madsen.

At least 55 records · Page 3Linked to original sources
PubMed1993

Determination of the rate constants k1 and k2 of the Linderström-Lang model for protein amide hydrogen exchange. A study of the individual amides in hen egg-white lysozyme.

The pH dependence of the amide/solvent hydrogen exchange of individual amide groups in hen egg-white lysozyme has been studied by nuclear magnetic resonance spectroscopy. Lysozyme has been used here as a model for a globular protein to re-examine the hypothesis for the amide/solvent hydrogen exchange reaction proposed by K. Linderstrøm-Lang and described in detail by Hvidt and Nielsen. The work has been focused on the most slowly exchanging amide at the temperature of 21 degrees C and in the pH range between 4 and 8. Exchange rates have been measured for 64 of the 126 amide protons and the pH dependence has been determined for 52 of these. The amides examined represent a sample that includes all the types of secondary structure and they are placed in the globular structure in a range of 3.2 A to 8.5 A from the closest water molecule on the surface. The measured exchange rates at pH 6 have been compared to these structural parameters and the results suggest that the rate constants are determined partly by the distance to the surface and partly by the type of secondary structure the amide is engaged in. Near the surface and in the very interior the distance to the surface seems to be rate-determining. Between the extremes the type of secondary structure is rate determining. The pH dependent exchange of the examined amides was shown to be in agreement with the Linderstrøm-Lang model. For each of the amides examined the rate constants for the opening and the closing reaction in the first reaction step of the Linderstrøm-Lang model has been calculated and compared to structural parameters.

Amides↗
PubMed1992

Induction of transplantation tolerance in adults using donor antigen and anti-CD4 monoclonal antibody.

The T-cell-mediated immune response usually results in the rapid destruction of organ allografts transplanted between murine strains incompatible for major and minor histocompatibility antigens. This response may be modified by pretreatment with either donor-specific antigen or anti-CD4 monoclonal antibody. Previous work by others has shown that combined treatment of mice with soluble protein antigens and anti-CD4 monoclonal antibody can produce antigen-specific B cell unresponsiveness that continues long after the nonspecific immunosuppressive effect of the mAb treatment has resolved. Following this principle we have shown that adult C3H/He mice can be made specifically unresponsive to vascularized C57BL/10 cardiac allografts by pretreating the recipient with donor alloantigen under the cover of a brief course of mAb against CD4. A full-dose response analysis shows that the dose of mAb is critically important for the successful induction of tolerance. Tolerance induction using this protocol is dependent on treatment with donor major histocompatibility complex antigens and occurs in the presence of marked depletion but not complete elimination of the CD4+ T cell subset. The unresponsiveness to alloantigen is antigen specific, as determined by the ineffectiveness of third-party (C57BL/10) alloantigen when combined with anti-CD4 mAb to induce long-term survival of BALB/c allografts in C3H/He recipients. The tolerant state is specific and effective in the long-term as indicated by the specific acceptance of C57BL/10 skin grafts in recipients with surviving C57BL/10 cardiac allografts. This study provides a simple method for the successful induction of specific transplantation tolerance in the adult across a full H-2 major and minor antigen mismatch strain combination. The results illustrate the important role of the CD4 molecule in the T cell response to alloantigen in vivo and suggest possibilities for the therapeutic manipulation of complex immune reactions.

Animals↗
PubMed1991

Refinement of the three-dimensional solution structure of barley serine proteinase inhibitor 2 and comparison with the structures in crystals.

The three-dimensional structure of barley serine proteinase inhibitor, CI-2, has been determined using nuclear magnetic resonance spectroscopy. The present structure determination is a refinement of the structure previously determined by us, using in the present case stereo-specific assignments, and a virtually complete set of assignments of the two-dimensional nuclear Overhauser spectrum. The structure determination is based on the identification of more than 1300 nuclear Overhauser effects, of which 961 were used in the structure calculation as distance restraints, and on 94 dihedral angle restraints, of which 31 are for chi 1 angles in defined chiral centers. These have been used to calculate a series of 20 three-dimensional structures using a combination of distance geometry, simulated annealing and restrained molecular dynamics. Each of the 20 structures was in agreement within less than 0.5 A of each of the distance restraints and with all dihedral angle restraints. When compared to the geometric average structure of the 20 refined structures the root-mean-square differences for the backbone atoms were 0.8 (+/- 0.2) A and for all atoms were 1.6 (+/- 0.2) A. By comparison, the values obtained for the structures determined previously were 1.4 (+/- 0.2) A and 2.1 (+/- 0.1) A, respectively. The structures were also compared to the structure determined in the crystalline state by X-ray diffraction showing root-mean-square differences of 1.6 (+/- 0.2) A and 2.8 (+/- 0.2) A for the backbone and all atoms, respectively. Common features of the solution structure and the two crystal structures are the four-stranded beta-structure, composed of a pair of parallel strands, and three pairs of antiparallel beta-strands flanked on one side by a 12-residue alpha-helix and on the other side by a loop containing the serine proteinase binding site. The new analysis of the structure has revealed an additional pair of antiparallel beta-strands, consisting of residues 65 to 67 and 81 to 83, that was not seen in either of the crystal structures or the previous solution structure. Identification of this was based on nuclear magnetic resonance evidence for the hydrogen bond (67HN to 81CO) not reported previously. Also the presence of a bifurcated hydrogen bond involving Phe69 CO and HN atoms of Ala77 and Gln78 was observed in solution but not in crystals. Minor differences between the two structures were observed in the phi-angles of residues Met59 and Glu60 in the inhibitory site.

Crystallography↗
PubMed1991

Ankle fractures and alcoholism. The influence of alcoholism on morbidity after malleolar fractures.

The postoperative morbidity after osteosynthesis of malleolar fractures was investigated retrospectively by comparing 90 alcohol abusers with 90 controls. The two groups were selected from 626 male patients and were matched regarding trauma, treatment for cardiovascular, pulmonary and endocrine diseases, age, weight, smoking habits, anaesthesia and duration of surgery. The alcohol abusers developed significantly more early complications, especially infections, after surgery. Follow-up at six, nine and 12 weeks after surgery also revealed a significantly higher morbidity among the alcoholics.

Alcohol Drinking↗
PubMed1988

Immunological unresponsiveness induced by recipient cells transfected with donor MHC genes.

Immunological unresponsiveness to allografts can be achieved by pretreating recipients with cells (whole blood, erythrocytes, lymphocytes) expressing donor-specific histocompatibility antigens. Attempts to determine the relative contribution of class I or class II major histocompatibility antigens and/or minor histocompatibility (miH) antigens towards the induction of an unresponsive state have yielded conflicting results. We have addressed this issue using DNA-mediated gene transfer to introduce murine class I or class II major histocompatibility complex (MHC) genes from the organ donor into cells of recipient origin. This allowed murine recipients of cardiac allografts to be pretreated with either donor cells sharing only an isolated class I or class II MHC locus product with the donor organ. We show that pretreatment with either donor class I or class II antigens prolongs survival of cardiac allografts, and that the capacity of a particular donor MHC antigen to induce unresponsiveness is the product of its intrinsic immunogenicity and the antigen load delivered during pretreatment. These results explain discrepancies in earlier studies of antigen-induced unresponsiveness and suggest a novel approach to specific immunosuppression in clinical transplantation.

Animals↗
PubMed1984

Adaptive processes controlling sensitivity of short-wave cone pathways to different spatial frequencies.

The sensitivity of the short-wave cone pathways was measured with violet interference gratings on monochromatic adapting fields. Spectral field sensitivity functions for test gratings of 2, 4 and 8 c/deg approximately matched Stiles' pi 3 function, which presumably reflects light-adaptation of the short-wave cones. Previous work had suggested that field sensitivity varies as a function of test spatial frequency, but this now seems an artifact of spatial adaptation. (The present study shows the pathway is highly susceptible to spatial adaptation induced by fine patterns.) For various spatial frequencies that affect the short-wave pathway, signals also pass through a cancellate adaptation site where signals from the short-wave and the middle- and long-wave cones act in opposition. Transient inputs in either opponent direction polarize or desensitize the opponent site. Additional transient inputs of the opposite sign then reduce the polarization and increase sensitivity. Such effects were demonstrated with test gratings as high as 12 c/deg. Transient effects at the opponent site are particularly evident at higher spatial frequencies.

Adaptation, Ocular↗
PubMed1984

Opponent-movement mechanisms in human vision.

A vertical grating that sinusoidally reverses contrast can be synthesized from two identical component gratings that move with equal velocities in opposite directions (leftward and rightward). Such a counterphase grating is used as a suprathreshold masking pattern. When the mask is of low spatial frequency and is modulated rapidly, a test pattern consisting of an increment of the rightward component and an equivalent simultaneous decrement of the leftward component is highly detectable compared with simultaneous increments or decrements of both components. The visibility of the opponent-movement test signal is strongly facilitated by high-contrast masks. This facilitation is accompanied by a high sensitivity for judging the direction of motion of the test. These results show that certain detection mechanisms are highly sensitive to the difference of the rightward and leftward components. However, when the mask is of threshold contrast, the rightward- and leftward-moving test components appear to be detected independently. A high-contrast grating that rapidly moves in one direction strongly masks gratings moving in the same or opposite direction; this shows that moving patterns are not detected by unidirectional mechanisms when contrast is clearly suprathreshold. The results may be explained by a model with mechanisms that are excited by one direction of motion and inhibited by the opposite direction.

Discrimination Learning↗
PubMed1980

Spatial adaptation of short-wavelength pathways in humans.

Color-selective spatial adaptation of the short-wavelength, or blue-sensitive, pathway was demonstrated. The adaptation was orientation selective and strongly monocular. Adaptation was assessed by measuring visibility thresholds for monochromatic gratings in subjects adapted to high-contrast violet gratings designed to stimulate only blue-sensitive cones. The results showed spatially selective, adaptable channels within the short-wavelength pathway.

Adaptation, Physiological↗
PubMed1978

Apparent saturation of blue-sensitive cones occurs at a color-opponent stage.

Response saturation of blue-sensitive cone pathways was studied by measuring increment thresholds for violet test flashes on flashed violet fields in the presence of a steady yellow "auxiliary" field of constant radiance. Adding intense yellow field flashes to the violet field flash could eliminate or reduce response saturation (greatly reduce threshold), whereas "negative" yellow field flashes drove the mechanism to further saturation. The response saturation is thus not, in general, controlled exclusively by independent blue-sensitive cones but by spectrally opponent mechanisms that receive opposite-signed signals from blue-sensitive cones and from green-or red-sensitive cones. These results add to a growing number of studies that demonstrate that detection of signals from blue-sensitive cones is largely through a color-opponent pathway.

Action Potentials↗