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Biomedical subjects

A Larsen

Publications and source records attributed to A Larsen.

At least 127 records · Page 7Linked to original sources

Chloroquine in long-term treatment of rheumatoid arthritis.

The effect of long-term (18-70 months) chloroquine treatment 250 mg daily, in rheumatoid arthritis (RA) was studied in 20 patients. Sedimentation rates were significantly reduced, as compared to a reference group of 10 RA patients on no treatment of disease modifying anti-rheumatic drugs. Radiographical progression of the disease was low in the majority of chloroquine-treated patients but not significantly different from the finding in the patients of the reference group. Rapid radiographical progression during 2-3 years was, however, observed in 5 patients despite chloroquine treatment.

Adult↗

Digitoxin kinetics and renal excretion in children.

Digitoxin kinetics were investigated in 11 children, three girls and eight boys, with a mean age of 7.1 yr (5.9 to 9.2). Five children received digitoxin, 17.5 to 20 micrograms/kg IV, and six other children received 20 micrograms/kg as an oral solution. Digitoxin was given as a single dose 24 to 48 hr after cardiac surgery, and patients were monitored in an intensive care unit for 24 hr. Serum and urine digitoxin concentrations were determined by radioimmunoassay. Children had larger apparent volumes of distribution (1 l/kg) than adults (0.57 l/kg). Mean serum elimination t 1/2 was 6.4 days in children (3 to 11.2) and 8.2 days in adults (5.9 to 11.3). Total body clearance was much greater in children (0.085 ml X min-1 X kg-1) than in adults (0.036 ml X min-1 X kg-1). This was because of an increase in metabolic clearance, although there was no difference in renal clearance in children and adults. Absolute oral bioavailability, measured by comparing serum AUCs after intravenous and oral doses, was complete. Peak serum concentrations of 23 to 50 ng/ml developed 90 to 120 min after the oral dose. A single digitalization dose of 20 micrograms/kg was well tolerated and did not induce arrhythmias.

Administration, Oral↗

Visual apparent movement: transformations of size and orientation.

Sequential alternation between same-shaped stimuli differing in size (size ratio s) and orientation (angular difference v) produced a visual illusion of translation in depth and concurrent rotation. The minimum stimulus-onset asynchrony required for the appearance of a rigidly moving object was approximately a linearly increasing function of (s-1)/(s+1) for simple translation in depth and a linearly increasing function of v for simple rotation. The extrapolated zero intercept was lower for translation than for rotation, but estimated transformation times were additive in combined transformations. The results suggest that (a) the processes of apparent translation in depth and apparent rotation are individually sequential-additive in structure, and (b) apparent translations and rotations are combined by fine-grained alternation of steps of apparent translation and steps of apparent rotation. Similar principles account for recent data on imagined spatial transformations of visual size and orientation.

Depth Perception↗

An altered DNA conformation detected by S1 nuclease occurs at specific regions in active chick globin chromatin.

The single-stranded activity of S1-nuclease cleaves globin chromatin in red cell nuclei in specific regions. The cleavages are observed only in tissues in which the globin genes are active, and they "switch" to reflect the switching pattern of globin-gene expression in embryonic and adult red cells. The positions of the S1 cleavages in the beta- and alpha-globin chromatin correspond to the general region of known DNAase I-hypersensitive sites, but can be distinguished in detail. When DNA segments containing these regions are subcloned into pBR322 and the supercoiled molecules are treated with S1, similar sites are cleaved in the purified supercoiled (but not linear) recombinant plasmid DNA. However, the dominant S1 cutting sites are shifted in the plasmid vis-a-vis the chromatin. We believe that some aspect of DNA sequence is translated into an altered DNA structure in chromatin and that it is this altered structure that is recognized by s1 nuclease and possibly by certain chromosomal proteins. Several physical properties reflected in the S1 digestion of supercoiled plasmids suggest a mechanism for generating differences in daughter cells during development.

Animals↗

Velocity constraints on apparent rotational movement.

The visual illusion of apparent rigid rotation was produced by sequential alternation of two views of the same object in different orientations. The minimum stimulus-onset asynchrony required for the appearance of rigid rotation was a linearly increasing function of the angular difference in orientation between the two views. Variation in the size of the object affected the zero-intercept of the function, but the slope was virtually constant. The slope invariance suggests that the appearance of rigid rotation is constrained by an upper bound on the apparent angular velocity of the object as a whole, rather than a bound on the linear velocity of its parts.

Humans↗

Contact sensitivity in mice evaluated by means of ear swelling and a radiometric test.

Contact sensitivity to picryl chloride was investigated by means of the ear swelling test and a radiometric test in order to establish optimal experimental conditions for these assays. Contact sensitivity was demonstrated as soon as 2 days after sensitization, with a maximum reaction 3-4 days after sensitization, when a 48 hr test reaction was registered. The test reaction was followed for 72 hr and maximum was arrived at after 24 hr and 48 hr for the ear swelling test and the radiometric test, respectively. Optimal sensitization was reached with a 7% solution of picryl chloride and a maximum test reaction was found with 0.75-1.0% picryl chloride. It is concluded that both assays measure contact sensitivity in quantitative terms and a future replacement of the guinea pig maximization test is discussed.

Animals↗

Alpha-Globin-gene switching during the development of chicken embryos: expression and chromosome structure.

We have analyzed the chromosome structure and expression of the alpha-gene cluster in developing chicken embryos. Using recombinant lambda clones (Dodgson and Engel, 1980), we show a striking relationship between chromosomal regions that are unmethylated, regions that are DNAase I-sensitive and regions that are transcribed. Adjacent regions at both the 5' and 3' sides of the active alpha genes are methylated and relatively insensitive to DNAase I. The active alpha subdomain defined by these assays begins right at the 5' side of the first alpha gene (alpha D) in the active cluster in definitive red cells and extends through a 1.5 kb spacer, into the second alpha gene (alpha A), and 1.5 kb beyond the 3' side of that gene. The sharp boundaries of this subdomain suggest that specific DNA sequences may establish its borders. The extension of the active chromosomal domain beyond the most stable nuclear transcript suggests that transcription may proceed beyond the 3' ends of both alpha A and alpha D. This has been verified by in vitro runoff nuclear transcription. Presumably, poly(A) addition occurs before transcription is terminated. During the switch from the primitive to definitive lineage of erythroblasts, the so-called U gene becomes inactive. This inactivity is reflected in its assembly into a more DNAase-resistant structure. The associated DNA also becomes methylated, and no transcription is detectable by endogenous RNA polymerases. A DNAase I-hypersensitive region at the gene becomes inactivated after the switch to the definitive lineage.

Animals↗

The calcium carbimide-ethanol interaction: lack of relation between electroencephalographic response and cerebrospinal fluid acetaldehyde.

Penetration of acetaldehyde into cerebrospinal fluid (CSF) was studied in healthy human volunteers during calcium carbimide-ethanol interaction. CSF was sampled via lumbar puncture and blood from a cubital vein. CSF and blood acetaldehyde concentrations varied from 1 to 41 and from 22 to 138 mumol/l, respectively. The results indicate that acetaldehyde penetrates the human blood-liquor barrier. Computer analysis of electroencephalograms (EEGs) recorded during the interaction showed reduction in alpha activity with a concomitant increase in delta activity. The changes were similar to those previously observed during 'normal' ethanol intoxication.

Acetaldehyde↗

Physiological control of phosphorylation ribosomal protein S6 in Mucor racemosus.

The level of phosphorylation of ribosomal protein S6 increased with accelerating rates of growth and protein synthesis in Mucor racemosus. Lowered levels of phosphorylation were seen under conditions of metabolic shift-down or the onset of stationary phase, and no phosphorylation was detected in sporangiospores. Changing metabolic states, changing intracellular levels of adenosine triphosphatase, and the level of phosphorylation of protein S6 were correlated in M. racemosus.

Adenosine Triphosphate↗

Digitalis glycosides in serum, urine, and cerebrospinal fluid, determined with a commercial radioimmunoassay.

We evaluated a commercial (Clinical Assays, Inc.) 125I radioimmunoassay for digitoxin for use in measuring cardiac glycosides in serum, buffer, urine, and cerebrospinal-fluid samples. We also assessed interference of seven cardioactive metabolites of digitoxin, including digoxin, with the assay. The precision of the assay was adequate for all matrixes studied for glycoside concentrations less than 5 microgram/L. Reactivity in the assay was dependent on the nature of the matrix: buffer and serum samples containing digitoxin showed a stronger reactivity than did samples of urine and cerebrospinal fluid. Patients' samples must therefore be analyzed with a standard curve prepared by use of the same matrix. The digitoxosides of digitoxin showed a slightly higher reactivity in the assay than did digitoxin itself, but digitoxigenin showed a 50% lesser reactivity. Digoxin, its digitoxosides, and digoxigenin hardly react at all in the assay and so do not interfere with digitoxin determinations.

Animals↗

Peripheral neuropathy and myopathy. An experimental study of rats on alcohol and variable dietary thiamine.

The effects of variable dietary thiamine concentrations (deficient, normal, surplus) on the development of alcoholic neuromyopathy in rats exposed for 36 weeks to 10-25% (v/v) ethanol or water (control group) as the sole drinking fluid were studied by histological and electrophysiological methods. Abnormalities in the structure of the sciatic nerve (phagocytosis, myelin abnormalities, increase in nonspecific cholinesterase activity) and tibial muscles (angular atrophic fibers, group atrophy, fibre necrosis) developed more frequently in animals on diets deficient in thiamine than in animals on diets with normal or surplus thiamine, and more frequently in animals drinking alcohol and water than in those drinking water alone. No differences were observed between the different groups in the number of perivascular sympathetic nerves, in the motor nerve conduction velocities and in the muscle fibrillation potentials. Thus, thiamine deficiency, established as a significant reduction of red blood cell transketolase activity, seems to have a deleterious effect on the peripheral nerves and muscles. The effect is enhanced by the simultaneous consumption of ethyl alcohol.

Alcoholism↗

Ribosomal proteins of the dimorphic fungus, Mucor racemosus.

Ribosomal proteins of the dimorphic fungus Mucor racemosus were isolated and characterized by 2-dimensional gel electrophoresis. Proteins from ribosomes of the yeast and mycelial phase were compared, and were found to be qualitatively indistinguishable. The only consistent difference in the patterns of proteins was in a protein of the 40S subunit, S-6. This protein was phosphorylated in yeast and hyphae forms, but not in asexual sporangiospores. Studies on protein S-6 showed that it contained 3 phosphate residues per molecule of protein when maximally phosphorylated. In this form 3 different tryptic peptides were shown to contain a single phosphoserine. The S-6 protein also existed in forms containing 1 or 2 phosphates per molecule, depending on growth conditions.

Amino Acid Sequence↗

Disopyramide plasma levels in cardiac patients on maintenance therapy.

The antiarrhythmic agent disopyramide, in a dosage of 200 mg/8 h, was given to 7 cardiac patients. The drug was fairly rapidly absorbed, and the mean peak plasma concentration (3.5 microgram/ml) was measured 1 h after administration of the first dose. The mean biological half-life (7.8 h) was slightly prolonged compared to that reported in normal volunteer subjects. Mean steady state plasma concentrations within the therapeutic range were attained 24--32 h after the start of medication. The fluctuations in the plasma levels were in the order or 30 percent; however, a wide spread of the values was observed. The drug was well tolerated.

Adult↗