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Biomedical subjects

K Bartels

Publications and source records attributed to K Bartels.

17 recordsLinked to original sources

Temperature- and pressure-dependent phase behavior of monoacylglycerides monoolein and monoelaidin.

We used x-ray and neutron diffraction to study the temperature- and pressure-dependent structure and phase behavior of the monoacylglycerides 1-monoelaidin (ME) and 1-monoolein (MO) in excess water. The monoacylglycerides were chosen for investigation of their phase behavior because they exhibit mesomorphic phases with one-, two-, and three-dimensional periodicity, such as lamellar, an inverted hexagonal and bicontinuous cubic phases, in a rather easily accessible temperature and pressure range. We studied the structure, stability, and transformations of the different phases over a wide temperature and pressure range, explored the epitaxial relations that exist between different phases, and established a relationship between the chemical structure of the lipid molecules and their phase behavior. For both systems, a temperature-pressure phase diagram has been determined in the temperature range from 0 to 100 degrees C at pressures from ambient up to 1400 bar, and drastic differences in phase behavior are found for the two systems. In MO-water dispersions, the cubic phase Pn3m extends over a large phase field in the T,p-plane. At temperatures above 95 degrees C, the inverted hexagonal phase is found. In the lower temperature region, a crystalline lamellar phase is induced at higher pressures. The phases found in ME-water include the lamellar crystalline Lc phase, the L beta gel phase, the L alpha liquid-crystalline phase, and two cubic phases belonging to the crystallographic space groups Im3m and Pn3m. In addition, the existence of metastable phases has been exploited. Between coexisting metastable cubic structures, a metric relationship has been found that is predicted theoretically on the basis of the curvature elastic energy approximation only.

Biophysical Phenomena

Response to 35% CO2 in patients with chest pain and angiographically normal coronary arteries.

OBJECTIVES: Several interview studies have suggested that panic disorder (PD) exists in patients with angiographically normal coronary arteries (NCA). Interview studies require corroboration by other studies in order to validate them. The purpose of this study is to test whether response to the inhalation of 35% CO2 reliably discriminates between PD and non-panic disorder patients in this population. METHOD: Three groups were studied: six with NCA and PD, five with NCA and no PD, and ten in the control group. All subjects breathed room air, then 35% CO2 in a single-blind fashion. Each completed the Acute Panic Inventory (API) before and during the procedure. RESULTS: The NCA-panic group scored significantly higher than the other two groups on the Acute Panic Inventory from baseline to post-inhalation. CONCLUSION: Despite several methodological limitations including a relatively small number people in each cells, 35% CO2 was shown to trigger more intense responses in panic patients, thus helping to validate the interview findings.

Administration, Inhalation

Follow-up status of patients with angiographically normal coronary arteries and panic disorder.

Cardiology patients with normal coronary angiography demonstrate continuing and substantial social, health, and work disability. We hypothesized that the diagnosis of panic disorder would mark those for whom continuing disability is most likely. We interviewed 72 such patients at the time of their normal angiogram, and then again an average of 38 months later. Those with panic disorder (n = 36) demonstrated significantly more disability at follow-up than did the other study patients. We conclude that those patients with normal angiograms who have panic disorder are more disabled than those who do not have panic disorder. Panic disorder in psychiatric samples has been shown to be highly treatable. Therefore, early identification and treatment of panic disorder in this group is likely to minimize the suffering associated with this condition.

Adult

Efficacy of flecainide in pacing-induced sustained ventricular tachyarrhythmias: correlation to clinical parameters and tachycardia-characteristics.

Seventy-two patients with sustained ventricular tachycardia or syncope of unknown origin underwent electrophysiologic evaluation before and after therapy with flecainide (200-300 mg day-1). In all patients, sustained ventricular tachycardia or ventricular fibrillation was inducible during control electrophysiologic study. During flecainide therapy, sustained ventricular tachycardia (VT) was no longer inducible in 18 patients (25%) whereas in 54 patients, VT was still inducible. In five of the latter patients, VT became more difficult to induce (overall efficacy 32%). The rate of VT decreased from 214 +/- 49 beats min-1 during the control electrophysiologic study to 178 +/- 48 beats min-1 during flecainide (P less than 0.01). The ERP of the right ventricle increased from 251 +/- 27 ms during the control study to 267 +/- 34 ms on flecainide (P less than 0.01). Mean ejection fraction and mean LVEDP did not differ between responders and non-responders, yet the presence of a left ventricular aneurysm correlated with a lack of antiarrhythmic response to flecainide. VT rate as well as VT morphology during the control study discriminated between responders and non-responders; 11% of patients with VT-rate less than or equal to 230 beats min-1 responded to oral flecainide compared with 31% with a VT rate greater than 230 beats min-1 at control. 26% with induced monomorphic VT responded, compared with 100% with induced VF during the control study. 18 of 23 responders were discharged on flecainide. During a mean follow-up of 26 +/- 18 months, two patients experienced a recurrence of VT and in one patient, flecainide had to be discontinued due to side-effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Heavy riboflavin synthase from Bacillus subtilis. Particle dimensions, crystal packing and molecular symmetry.

Heavy riboflavin synthase from Bacillus subtilis is an enzyme complex consisting of approximately three alpha-subunits (Mr 23.5 X 10(3)) and 60 beta-subunits (Mr 16 X 10(3)). The enzyme has been crystallized from phosphate buffer in a hexagonal crystal modification that belongs to space group P6(3)22. The asymmetric unit of the crystal cell contains ten beta-subunits. The structure of this unusual 10(6) Mr protein has been studied by small-angle X-ray scattering, electron microscopy of three-dimensional crystals, and crystallographic methods. The scattering curves can be interpreted in terms of a hollow sphere model with a ratio of inner and outer radius of 0.3:1. A diameter of 168 A was estimated from the scattering curves, in close agreement with electron microscopic studies. An aggregate with the stoichiometry beta 60, which was obtained by ligand-driven reaggregation of isolated beta-subunits, showed similar shape and dimensions, but a larger value for the ratio Ri/Ra. Electron micrographs of freeze-etched enzyme crystals showed approximately spherical molecules, which were arranged in hexagonal layers. The lattice constants found from the micrographs are in good agreement with the values derived from X-ray diffraction data. Rotation function calculations in Patterson space showed a set of peaks for 2-fold, 3-fold and 5-fold local rotation axes, accurately consistent with icosahedral symmetry and with the particle orientation A shown in the Appendix. The crystal packing can be described as follows: enzyme particles with icosahedral symmetry (point group 532) are located at points 32 of the hexagonal cell, corresponding to positions (0, 0, 0) and (0, 0, 1/2) on the 6-fold screw axes. From the data reported, it may be concluded that the enzyme structure can be described as an icosahedral capsid of 60 beta-subunits with the triangulation number T = 1. The alpha-subunits are located in the central core space of the capsid, but their spatial orientation is incompletely understood.

Bacillus subtilis

Immunogenic activity of gonococcal protein I in mice with three different lipoidal adjuvants delivered in liposomes and in complexes.

For several reasons the major outer membrane protein from Neisseria gonorrhoeae (gonococcal protein [PI]) is an attractive component for a gonococcal vaccine. This paper describes the influence of two different physical forms of PI on its immunogenic activity. To this end PI was delivered in liposomes and in protein-detergent complexes. In both forms PI was present in a multimeric form. The liposomes were composed of phosphatidylcholine and cholesterol. The effect of dicetylphosphate as a negatively charged amphiphile and three lipoidal adjuvants was investigated. Two lipoidal adjuvants (Avridine and dimethyldioctadecylammoniumbromide) were positively charged amphiphiles, whereas the third one (tridecyl N-acetylmuramyl-L-alanyl-D-isoglutaminate) was neutral. The protein-detergent complexes were also tested in the presence of the lipoidal adjuvants and in an AlPO4-adsorbed form. The liposome preparations were characterized for their size, charge, and residual amount of detergent. The immunogenic activity of PI in all forms was tested in mice. The results of the antibody assays showed that PI in the liposomes was more immunogenic than PI in the complexes. A second dose with liposomes induced only a small booster effect, whereas such a dose with the complexes produced pronounced booster effects. The incorporation of the positively charged lipoidal adjuvants in the liposomes resulted in enhanced booster effects. The highest immunogenic activity of PI after two injections, however, was observed in the complexed form adsorbed to AlPO4.

Animals

Di-n-propylacetate-induced abstinence behaviour as a possible correlate of increased GABA-ergic activity in the rat.

Administration of di-n-propylacetate (DPA), an inhibitor of SSA-dehydrogenase, produces in naive rats abstinence behaviour which can be blocked by morphine and bicuculline and may be useful as a behavioural correlate of increased GABA-ergic activity. The usefulness of this model has been demonstrated by studying the effect of bicuculline, picrotoxin, strychnine, morphine, aminooxyacetic acid, 3-mercaptopropionate and thiosemicarbazide on DPA-induced abstinence behaviour. Behaviour was suppressed both by bicuculline or picrotoxin, while the selective glycine antagonist strychnine was ineffective. A comparable syndrome could not be evoked by treatment with aminooxyacetic acid, a GABA-transaminase inhibitor, indicating that the effect of DPA was not caused by inhibition of this enzyme. Instead, aminooxyacetic acid suppressed the DPA-induced abstinence behaviour, suggesting that two GABA-ergic systems with opposite effects on behaviour can be distinguished. The syndrome was also suppressed by convulsant doses of 3-mercaptopropionate, while thiosemicarbazide was ineffective. Abstinence behaviour was further suppressed by morphine with an ED50 of 0.5 mg/kg and this action could be clearly separated from its depressant effect on locomotor activity in non-treated animals. These results suggest that morphine receptors may be involved in DPA-induced abstinence behaviour. Based on these experiments a model has been proposed for GABA-ergic terminals being under the inhibitor influence of GABA-ergic autoreceptors. It is proposed that DPA-induced abstinence behaviour may be useful as a model of increased GABA-ergic activity to aid study of the regulation and properties of the GABA-ergic system in vivo.

3-Mercaptopropionic Acid

Subunit symmetry of tetrameric phosphorylase a.

Native crystallographic data of tetrameric phosphorylase a crystals, space group P21, have been collected photographically to 3 A resolution. These data have been used in Patterson search methods in reciprocal and real space. The tetramers were found to exhibit molecular 222 symmetry. The cross vector between the centres of the two symmetry related tetramers in the unit cell was determined by two different translation function methods. On the basis of these rotation and translation function results a model for the arrangement of monomers within the tetramer and of tetramers in the unit cell is proposed; The 222 symmetry of the tetrameric molecule is found only when high resolution diffraction data are included (i.e. higher than 6 A). At lower resolution other symmetries dominate. Calculations with the proposed model have shown that these spurious symmetries result from the nonspecific overlap of protein-protein and solvent-solvent cross vectors. These results emphasize the importance of high resolution data when noncrystallographic symmetry of globular proteins is studied.

Chemical Phenomena

The analysis of biological shape changes from multidimensional dynamic images.

A technique for modeling shape changes in a time series of biological images of arbitrary dimension is described. The technique consists of first segmenting the image to locate the specimen, and then parametrizing the specimen in the initial image with an orthogonal material coordinate system. The deformation of the material coordinate system caused by the changing shape of the specimen is then solved for by minimizing an energy functional. The energy functional is a linear combination of a brightness continuity term and a shape change term. A parameter lambda, weights the brightness continuity against the shape change smoothness. The best value to use for lambda is chosen as the value that minimizes the mean square error between the image derived from the calculated shape change parameters and the corresponding actual image. A two-dimensional implementation by finite differences is given. Results from both two-dimensional confocal images, and two-dimensional synthetic images are presented. Our early work on a three-dimensional implementation is given.

Algorithms