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Biomedical subjects

B Bechtel

Publications and source records attributed to B Bechtel.

5 recordsLinked to original sources

Interaction of cationic amphiphilic drugs with lipid A: implications for development of endotoxin antagonists.

This report presents evidence for the interactions of several classes of cationic amphiphilic drugs including the phenothiazines, aminoquinolines, biguanides, and aromatic diamidines, with lipid A, the endotoxic principle of lipopolysaccharides. The interactions of the drugs were quantitatively assessed by fluorescence methods. The affinities of the drugs for lipid A parallel their endotoxin-antagonistic effects in the Limulus gelation assay. Dicationic compounds bind lipid A with greater affinity; the affinity of such molecules increases exponentially as a function of the distance between the basic moieties. The bis-amidine drug--pentamidine--examined in greater detail, binds lipid A with high affinity (apparent Kd: 0.12 microM), and LPS, probably due to simultaneous interactions of the terminal amidine groups with the anionic phosphates on lipid A. The sequestration of endotoxin by pentamidine reduces its propensity to bind to cells, and the complex exhibits attenuated toxicity in biological assays. These results have implications in the development of therapeutic strategies against endotoxin-related disease states.

Aminoquinolines↗

Addressing ethical boundaries among nurses.

Sexual intimacy is the primary boundary issue studied and reported in the literature, though it is not addressed directly in the ANA Code of Ethics. However, perhaps equally important are behaviors which may stem from nurses' meeting their own social and emotional needs through their work. Results of "Boundaries" workshops for more than 3000 nurses and other healthcare professionals are summarized. Recommendations are made, relative to both personal and professional behavior, along with a list of suggestions for nurse managers.

Codes of Ethics↗

Intragastric long-term pH-metry in hemodialysis patients. A study with famotidine.

The onset and duration of famotidine action were studied in 14 hemodialysis (HD) patients and 16 healthy controls (control group: CG) who were examined by ambulatory intragastric 24-hour pH-metry. 20 mg famotidine was administered i.v. 90 min after HD in the afternoon (AN; 2 p.m.; n = 8) or evening (E; 8 p.m.; n = 6), followed by a standard meal. Mean onset of action in the AN and E groups of the HD patients was 90.3 +/- 28.2 min and 98.8 +/- 29.8 min, and in CG patients 36.3 +/- 11.9 min and 53.6 +/- 22.3 min, respectively (p less than 0.05). Duration of action in the AN and E groups of the HD patients was 22.7 +/- 2.1 h and 21.6 +/- 2.6 h, and in CG patients 6.0 +/- 1.1 h and 11.4 +/- 1.6 h, respectively (p less than 0.05). Our study showed a retarded and prolonged action of famotidine in HD patients. The time of administration of famotidine had no effect on its action in HD patients. This is in contrast to normal subjects in whom evening administration delays the onset and prolongs the duration of famotidine action in comparison to afternoon administration.

Adult↗

Conformational analysis of the tumor-associated carbohydrate antigen 19-9 and its Lea blood group antigen component as related to the specificity of monoclonal antibody CO19-9.

A structural comparison between the synthetic, tumor-associated 19-9 tetrasaccharide, NeuAc alpha 2----3Gal beta 1----3GlcNAc(4----1 alpha Fuc)-O(CH2)8CO2CH3 and its Lea blood group antigen component, Gal beta 1----3GlcNAc(4----1 alpha Fuc)-O(CH2)8CO2CH3 was carried out by two-dimensional 1H NMR spectroscopy and hard-sphere energy calculations. Significant chemical shift differences between the two molecules were detected only for protons at or near the linkage site of NeuAc to the Lea trisaccharide core. Coupling constants for the ring protons of both molecules did not suggest major deviation from the 4C1 chair conformation for Gal and GlcNAc, the 1C4 conformation for Fuc, or the 2C5 conformation for NeuAc. Two-dimensional nuclear Overhauser enhancement experiments revealed through-space, inter-proton interactions that corresponded to some extent with those predicted by diffraction data and hard-sphere energy minimization programs for both saccharides. However, a significant number of interactions did not obey the distance dependence predicted from a rigid structure model. These data suggest that, while the average conformation of the 19-9 antigen's Lea core may be invariant to NeuAc alpha 2----3Gal linkage, the dynamics of the Lea trisaccharide are altered upon sialylation. Data also indicate that the terminal NeuAc linkage is more flexible than the inter-residue bonds of the core trisacharide. This analysis, in combination with the fact that the monoclonal anti-19-9 antibody CO 19-9 does not cross-react with the Lea antigen, provides evidence in favor of NeuAc as an epitope-creating unit involved directly at the antibody binding site. However, given the possible role of variable dynamics in epitope formation, these results do not preclude crucial roles in antibody recognition for regions on the 19-9 antigen that are distanced from NeuAc.

Antibodies, Monoclonal↗

Novel isoglobo-neolacto-series hybrid glycolipid detected by a monoclonal antibody is a rat colon tumor-associated antigen.

Isoglobotetraosylceramide (GalNAc(beta 1-3)Gal(alpha 1-3)Gal(beta 1-4)Glc (beta 1-1)Cer), the major glycolipid species in dimethylhydrazine-induced rat tumors of colorectal origin, was not detected in epithelial cells of normal colon but was present in the non-epithelial stroma and could be extracted from each of nine tumors studied. Monoclonal antibodies produced against isoglobotetraosylceramide detected this and another novel rat tumor-associated glycolipid not present in epithelial cells nor in non-epithelial stroma of normal rat colon (Brodin, T., Thurin, J., Strömberg, N., Karlsson, K.-A. and Sjögren, H.O. (1985) Eur. J. Immunol. 16, 951-956). This novel glycolipid was present in 8/9 of the studied tumors and was also present in two in vitro cell clones. These were originally obtained from a W49/T4 colon tumor isograft. The novel glycolipid was characterized by mass spectrometry, 1H-NMR, and methylation analysis as a hybrid between the isoglobo- and neolacto-series, with the structure GalNAc(beta 1-3)Gal(alpha 1-3)Gal(beta 1-4)GlcNA(beta 1-3)Gal (beta 1-4)Glc(beta 1-1)Cer.

Animals↗