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Biomedical subjects

E Arnold

Publications and source records attributed to E Arnold.

At least 109 records · Page 6Linked to original sources
PubMed1989

[The viewpoint of the elderly on the problems of aging].

Members of an university for the elderly conducted a survey among 730 elderly people in order to ascertain their living and housing conditions, their familiar and social relationship, their state of health, and how they envisaged their future should their independence become limited. This article describes the methodology of the study, the rich human and social experience gained by the researchers and it indicates the characteristics of the people surveyed, a high proportion of whom were very old and living alone and would thus be in a particularly precarious situation if their independence became limited owing to age or illness.

Activities of Daily Living↗
PubMed1989

Diethylthiocarbamic acid methyl ester. A potent inhibitor of aldehyde dehydrogenase found in rats treated with disulfiram or diethyldithiocarbamic acid methyl ester.

Rats were treated with disulfiram (Antabuse, DSF) or its metabolite diethyldithiocarbamic acid methyl ester (Me-DDC) and challenged with ethanol. The blood pressure response to ethanol was followed and blood was analyzed for DSF, Me-DDC and diethyldithiocarbamic acid (DDC). The rat liver aldehyde dehydrogenase (ALDH) isozyme activities were measured 2 hr after the ethanol challenge. Both treatments produced a significant fall in the blood pressure when challenged with ethanol, probably caused by a marked decrease in hepatocyte low Km and high Km activities. The mean plasma concentration ranges of Me-DDC and DDC were found to be 49-1241 nmol/l and 182-841 nmol/l, respectively, whereas DSF was undetectable. In addition, it was found that inactivation of hepatocyte low Km ALDH activity was dependent on preoxidation of Me-DDC by the microsomal cytochrome P-450 mixed function oxidases. Me-DDC was found to be oxidized under aerobic conditions in the presence of NADP to form diethylthiocarbamic acid methyl ester (Me-DTC). The structure was confirmed from its MS/EI fragmentation spectrum. Me-DTC was found to be a potent inhibitor of low Km ALDH when added to rat liver homogenate. The compound was also identified as a metabolite in rat blood collected from the DSF and Me-DDC treated rats, and in blood from human alcoholics on DSF treatment. Me-DTC appears to be more selective for the low Km isozymes whereas the opposite seems to be the case for the hydrolytic product, DTC.

Aldehyde Dehydrogenase↗
PubMed1989

[Descriptive single case analyses--a strategy for studying effectiveness correlations in psychotherapy].

A method of data analysis based on single case studies is investigated. It is intended to lead to empirically grounded hypotheses about the differences in effects of various therapeutic methods. The data bases are 16 documented therapies, eight of which are client-centered therapies and interactional behavior therapies respectively. Descriptive single case analyses were carried out in four steps: 1. documentation of single cases; 2. description of individual patterns of therapeutic effects; 3. comparisons within treatment groups; 4. comparisons between treatment groups. Results show that individual differences within groups exceed similarities, so that there is little evidence of a strong influence of the treatment method on individual patterns of therapeutic effects. This result leads to the conclusion that a typology of therapeutic processes should be based on more factors than the treatment method alone.

Behavior Therapy↗
PubMed1988

The use of molecular-replacement phases for the refinement of the human rhinovirus 14 structure.

The structure of human rhinovirus 14 has been refined, by the method of restrained least squares, to an R factor of 0.16 for various random samples between 6 and 3 A resolution with F greater than 3 sigma (F). As a first step the non-crystallographic symmetry parameters were optimized using the initial atomic model in a rigid-body refinement procedure. Phase determination by the molecular-replacement phase extension and refinement procedure was continued to 2.94 A resolution, employing the improved non-crystallographic symmetry operators. The resultant structure-factor phases and weights, together with the measured amplitudes, constituted the X-ray observations used in the restrained refinement. The Hendrickson-Konnert program system [Konnert & Hendrickson (1980). Acta Cryst. A36, 344-350] was modified to incorporate non-crystallographic symmetry constrains and structure-factor phases as observations. The non-bonded contacts between subunits related by non-crystallographic symmetry were also restrained.

Chemical Phenomena↗
PubMed1988

Ischemia-induced alterations of mitochondrial structure and function in brain, liver, and heart muscle of young and senescent rats.

Young and senescent rats (3 and 28-30 months old) were subjected to complete ischemia at 37 degrees C in order to study function and structure of mitochondria isolated from liver, heart muscle, and brain. The rates of energy-coupled respiration and ATP synthesis were found to decrease progressively in relation to time of ischemia. The respiratory rates in the absence of ADP (state 4 respiration) did not increase after exposure to ischemia, suggesting that ischemia primarily affects electron transport rather than the energy coupling system. Mitochondria of heart muscle were more affected by ischemia than mitochondria of brain and liver. Liver and heart muscle mitochondria obtained from young rats were found to be slightly more sensitive to short periods of ischemia than those isolated from senescent animals.

Adenosine Triphosphate↗
PubMed1987

The atomic structure of Mengo virus at 3.0 A resolution.

The structure of Mengo virus, a representative member of the cardio picornaviruses, is substantially different from the structures of rhino- and polioviruses. The structure of Mengo virus was solved with the use of human rhinovirus 14 as an 8 A resolution structural approximation. Phase information was then extended to 3 A resolution by use of the icosahedral symmetry. This procedure gives promise that many other virus structures also can be determined without the use of the isomorphous replacement technique. Although the organization of the major capsid proteins VP1, VP2, and VP3 of Mengo virus is essentially the same as in rhino- and polioviruses, large insertions and deletions, mostly in VP1, radically alter the surface features. In particular, the putative receptor binding "canyon" of human rhinovirus 14 becomes a deep "pit" in Mengo virus because of polypeptide insertions in VP1 that fill part of the canyon. The minor capsid peptide, VP4, is completely internal in Mengo virus, but its association with the other capsid proteins is substantially different from that in rhino- or poliovirus. However, its carboxyl terminus is located at a position similar to that in human rhinovirus 14 and poliovirus, suggesting the same autocatalytic cleavage of VP0 to VP4 and VP2 takes place during assembly in all these picornaviruses.

Antigens, Viral↗
PubMed1987

Comparison of the three-dimensional structure of two human rhinoviruses (HRV2 and HRV14).

An attempt has been made to build a model of human rhinovirus 2 (HRV2) based on the known human rhinovirus 14 (HRV14) structure. HRV2 was selected because its amino acid sequence is known and because it belongs to the minor rhinovirus receptor class as compared to HRV14, which belongs to the major class. Initial alignment of HRV2 with HRV14 based on the primary sequence and the knowledge of the three-dimensional structure of HRV14 showed that the most probable position of the majority of insertions and deletions occurred in the vicinity of the neutralizing immunogenic sites (NIm). Out of a total of 855 amino acids present in one copy of each of the capsid proteins VP1 through VP4 of HRV14, 411 are different between the two viruses. There are also 6 amino acid residues inserted and 14 residues deleted in HRV2 relative to HRV14. Examination of amino acid interactions showed several cases of conservation of function, e.g., salt bridges or the filling of restricted space. The largest variation amongst the residues lining the canyon, the putative receptor binding site, was in the carboxy-terminal residues of VP1.

Amino Acid Sequence↗
PubMed1987

Implications of the picornavirus capsid structure for polyprotein processing.

Mature picornaviral proteins are derived by progressive, posttranslational cleavage of a precursor polyprotein. These cleavages play a role in the control of virus functions. Although the processed termini are separated by as much as 75 A in the native virus capsid, the fold and arrangement of polypeptide chains in a protomer before proteolysis are likely to be similar to that found in the mature virus. The three-dimensional structures of rhinovirus and Mengo virus suggest that the cleavage sites within the protomeric precursor are in structurally flexible regions. The final proteolytic processing event, maturation of the virion peptide VP0 (also called peptide 1AB) appears to occur by an unusual autocatalytic serine protease-type mechanism possibly involving viral RNA basic groups that would serve as proton-abstractors during the cleavage reaction.

Capsid↗
PubMed1986

The site of attachment in human rhinovirus 14 for antiviral agents that inhibit uncoating.

WIN 51711 and WIN 52084 are structurally related, antiviral compounds that inhibit the replication of rhino (common cold) viruses and related picornaviruses. They prevent the pH-mediated uncoating of the viral RNA. The compounds consist of a 3-methylisoxazole group that inserts itself into the hydrophobic interior of the VP1 beta-barrel, a connecting seven-membered aliphatic chain, and a 4-oxazolinylphenoxy group (OP) that covers the entrance to an ion channel in the floor of the "canyon." Viral disassembly may be inhibited by preventing the collapse of the VP1 hydrophobic pocket or by blocking the flow of ions into the virus interior.

Antiviral Agents↗
PubMed1986

Toxicity of toxaphene in the rat and beagle dog.

Residues of the insecticidal mixture, toxaphene, have been found in Great Lakes fish. The purpose of the present study was to assess the subchronic toxicity of toxaphene in the rat and beagle dog. In the rat study, groups of 10 male and 10 female animals were fed diets containing 0, 4, 20, 100, or 500 ppm of the test compound for 13 weeks. No clinical signs of toxicity or spontaneous deaths were observed. Toxaphene treatment up to 500 ppm had no effects on weight gain or food consumption. The liver/body weight ratio and hepatic microsomal enzyme activities (phenobarbital type) were increased in both sexes fed 500 ppm of the test compound. Toxaphene at the highest dose also caused kidney enlargement in male but not in female rats. Dose-dependent histological changes were seen in the kidney, thyroid, and liver. Changes in the liver and thyroid were considered to be adaptative but the injury in the proximal tubules of the kidney was focally severe. Groups of six male and six female beagle dogs were fed toxaphene in gelatin capsules at 0, 0.2, 2.0, and 5.0 mg/kg body wt/kg body wt/day for 13 weeks. Food consumption and growth rate were not affected. All animals survived the entire treatment period. No clinical signs of toxicity were observed. The liver/body weight ratio and serum alkaline phosphatase were increased in dogs of both sexes fed 5.0 mg/kg. Mild to moderate dose-dependent histological changes were observed in the liver and thyroid. Toxaphene was accumulated in a dose-dependent manner in the fat and liver of dogs and rats. Based on the biochemical, histological, and residue data, it was concluded that the no-adverse-effect levels of the pesticide were 4.0 ppm (0.35 mg/kg) for the rat and 0.2 mg/kg for the dog.

Animals↗
PubMed1986

Effect of errors, redundancy, and solvent content in the molecular replacement procedure for the structure determination of biological macromolecules.

The power of molecular replacement as a tool for analyzing macromolecular structures such as viruses has been demonstrated by an increasing number of successful determinations. We examine here the effects of noncrystallographic redundancy, N; the fraction of solvent volume (1- U/V); error in structure amplitude measurements, R; the fraction, f, of the unique data that were measured; error in the description of the noncrystallographic symmetry; and definition of the molecular envelope. The formula P = (Nf)1/2/R(U/V) has been derived and represents the inherent phasing power (P) for a given problem. The ability of "solvent flattening" procedures to determine phases was analyzed and found to be analogous to the effect of noncrystallographic redundancy. However, in the limiting case, the effect of solvent flattening approaches the power of Sayre's equations.

Crystallography↗
PubMed1986

Pharmacokinetics of 14C-fenflumizole after intravenous administration to man.

The disposition of 14C-labelled fenflumizole was studied in five healthy subjects who received 0.1 mg/kg of fenflumizole as single intravenous doses. Radioactivity was measured in whole blood, plasma, urine and feces from prior to until 168 hours after dose administration. Chemical determinations of fenflumizole and its two demethylated derivatives in plasma were made by HPLC followed by fluorescence detection. Concentrations of fenflumizole calculated from radioactivity in plasma were consistently higher than from chemical determinations, suggesting the presence of metabolites. Radioactivity in blood cells decreased more slowly than in plasma. Plasma concentrations versus time could be described by a four-compartment model, with a terminal half-life of 119 hours (median). About 50% of the dose was excreted with the faeces, and about 4% was recovered in the urine. Unchanged fenflumizole in the urine accounted for 0.0001% of the total dose. Renal clearance of radioactive material decreased at low concentrations of radioactive compound in plasma, which may indicate changes in unbound fraction of drug and metabolites, or a saturable tubular reabsorption process. The slow elimination of fenflumizole is consistent with slow release from tissues and/or enterohepatic recycling.

Adult↗