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Biomedical subjects

D F Johnson

Publications and source records attributed to D F Johnson.

At least 73 records · Page 4Linked to original sources

Behavioral and hormonal responses to separation in infant rhesus monkeys and mothers.

Effects of social stimuli on behavioral and physiological responses were examined in infant rhesus monkeys at 4 and 9 months of age. Infants and mothers were removed from the social group and housed as dyads. Following this period, infants were removed and separated under four counterbalanced conditions: (a) totally isolated--placed in a holding cage for 24 hr; (b) mother present, no contact--housed in a single cage in view of their mother, no contact; (c) mother present, contact--similar to above, with mother in proximity to the infant; and (d) peer present--separated but in proximity to a peer. In the first experiment, the infants rarely vocalized when totally isolated but showed high rates of vocalization in the presence of the mother, both with and without contact. In the mother-present conditions, they failed to show a plasma cortisol response. In contrast, totally isolated infants showed a significant elevation in plasma cortisol. At 9 months of age, these infants were separated for 3 days under two different conditions: mother present and totally isolated. Once again, the infants that were totally isolated showed little vocalization but significant elevations in plasma cortisol. In contrast, infants separated in the presence of their mothers showed high vocalization rates but no cortisol response. The concepts of protest and despair are discussed as they relate to behavioral and physiological differences observed following different separation paradigms.

Adaptation, Physiological↗

Cloning and expression of apolipoprotein B, the major protein of low and very low density lipoproteins.

We report the cloning of cDNAs for rat liver apolipoprotein B (apo B) and the use of the cloned sequences to examine apo B expression at the level of mRNA in rat tissues. Fifteen putative apo B clones were identified by antibody screening of a rat liver cDNA library in the lambda gt11 expression vector. The identity of the clones was confirmed by immunological studies of the fusion protein products. All clones appear to contain sequences found only in apo B PI, the high molecular weight form of rat liver apo B. Blotting studies show that the clones hybridize to a single 20-kilobase liver mRNA species, sufficiently large to encode the entire apo B PI peptide, which is estimated to be 400 kDa in size. Apo B PI mRNA is abundant in liver and present in lower amounts in intestine but is absent in a variety of other tissues examined. This tissue distribution is consistent with that expected from studies on the in vivo synthesis of apo B. One clone, corresponding to a 240-base segment of the apo B PI mRNA, was sequenced and found to exhibit homology with a short region of rat apo E mRNA. Analysis of the secondary structure of the corresponding peptide did not show the preponderance of amphipathic alpha-helical structures characteristic of other apolipoproteins examined thus far.

Amino Acid Sequence↗

DNA sequence of the lactose operon: the lacA gene and the transcriptional termination region.

The lac operon of Escherichia coli spans approximately 5300 base pairs and includes the lacZ, lacY, and lacA genes in addition to the operator, promoter, and transcription termination regions. We report here the sequence of the lacA gene and the region distal to it, confirming the sequence of thiogalactoside transacetylase and completing the sequence of the lac operon. The lacA gene is characterized by use of rare codons, suggesting an origin from a plasmid, transposon, or virus gene. UUG is the translation initiation codon. A preliminary examination of 3' end of the lac messenger in the region distal to the lacA gene indicates several endpoints. A predominant one is located at the 3' end of a G + C-rich hairpin structure, which may be involved in termination of transcription or in post-transcriptional processing. An open reading frame of 702 base pairs is present on the complementary strand downstream from lacA.

Acetyltransferases↗

Effects of dietary nutrients and foraging costs on meal patterns of rats.

Rats were fed either a cereal-based or a purified casein-based diet in a foraging paradigm in which the costs of procurement and consumption were varied. The group offered the cereal-based diet consumed about 10% more calories than the group offered the casein-based diet, but both groups grew at the same rate. The intake of a control group offered a choice between the two diets was approximately 80% from the casein diet, and the growth of this group did not differ from that of the experimental groups. Variations in the cost of procurement and the cost of consumption affected the patterning of meals differentially for the two diets: changes in meal patterns tended to control the time and/or energy spent feeding. These results show that (1) meal patterns in the foraging paradigm are sensitive to subtle differences in diets, and (2) the amount of diet consumed (acceptance) and the choice between diets (preference) are determined by the economics of feeding and the nutritive quality of the foods, as well as by their palatability.

Animal Feed↗

The toxicologic evaluation of marcellomycin--an antineoplastic anthracycline antibiotic.

Dose-related toxicologic effects of marcellomycin, an antineoplastic anthracycline antibiotic, were observed in single-dose studies in mice iv (43.05-67.65 mg/m2) and dogs iv (41.0-90.2 mg/m2), and in multiple-dose studies in dogs iv (9.8-29.6 mg/m2 2X/week for 6 weeks) and rats sc (9 weekly doses at 26.2-72.2 mg/m2). Toxicity was primarily manifested by suppression of myeloid tissue, especially the erythrocytic and thrombocytic series, and lymphoid tissues. Initially a neutrophilic leukocytosis was observed in dogs and rats, which was considered possibly to be due to mobilization of the marginal and bone marrow neutrophil pools. In dogs, this was followed by a marked, dose-related neutropenia; and, in rats that died, there was marked depletion of bone marrow cells. Other toxicities observed included enteropathy, severe subcutaneous serofibrinous inflammatory edema and necrosis at injection sites, prostate and seminal vesicle atrophy, uterine hypoplasia, testicular and pancreatic degeneration, thyroid follicular proliferation and hemorrhage in various organs. In general, these toxicities were reversible in surviving animals during recovery periods. Significant cardiotoxicity was not demonstrated.

Animals↗

A comparison of growth inhibition of Tetrahymena furgasoni by C19 and C21 steroids.

The growth inhibition of Tetrahymena furgasoni (once known as "T. pyriformis W") by C19 and C21 steroids of similar structure was measured by determining cell population at 24 h and 48 h following addition of the steroid. A cis-fusion of the A/B rings junction, unsaturation at C-1,2, or C-4,5 and carbonyl substitution all enhanced inhibition, whereas the presence of two hydroxyl groups decreased inhibition. The results indicated that the transformation of C19 and C21 steroids by this protozoon may be part of a detoxication mechanism.

Androstenols↗

Comparisons between one-key and two-key versions of the sinewave schedule for pigeons.

When the rate of reinforcement for pigeons' key pecking varied over time following a sine waveform, performances were more consistent and reliable if a constant-rate reinforcement schedule was concurrently available on a second key than if only the sinewave-varying reinforcement schedule was available. In the two-key version, response rates clearly followed varying reinforcement rates with the same frequency, with no phase lag, and without breaks. In both versions, pecking rate was a power function of reinforcement rate. Sinewave-schedule performance waveforms qualified for engineering methods of frequency analysis and met criteria for a standard measurement system.

Journal Article↗

The toxicological evaluation of carminomycin - an antineoplastic anthracycline antibiotic.

Carminomycin, an anthracycline antibiotic discovered in the Soviet Union, possesses antitumor activity and is chemically related to adriamycin and daunorubicin. The toxic effects of carminomycin observed in single-dose toxicologic studies in mice iv (4.5-13.5 mg2) and po (18.9-52.2 mg/m2), rats iv (6.0-21.0 mg/m2), dogs iv (1.0-16.0 mg/m2) and po (16.0-80.0 mg/m2), Rhesus monkeys po (24.0-144.0 mg/m2); and in multiple-dose studies in dogs iv (18 doses 0..6-5.0 mg/m2, 2X/week) and rats sc (9 doses 3.0-12.0 mg/m2, 3X/week), were dose-related and primarily manifested as suppression of hematopoiesis. Other toxicities observed included nephrotoxicity, gastrointestinal toxicity, decreased spermatogenesis, decrease in size and activity of the prostate and seminal vesicles, and ovarian alterations. In general, these toxicities were reversible in surviving animals during recovery periods. Cardiotoxicity, similar to that seen with adriamycin sc (13 doses 12.0 mg/m2, 1X/week) was not observed with carminomycin sc (13 doses 6.0 mg/m2, 1X/week).

Animals↗

Unique long-acting antiglucocorticoid in whole and broken cell systems.

The biological properties of cortisol 21-mesylate (CM), an alkylating derivative of cortisol, were investigated in a line of rat hepatoma tissue culture (HTC) cells. CM appears to bind to glucocoticoid receptors in cell-free extracts because CM inhibits the specific binding of [3H]dexamethasone. However, in whole cells CM not only fails to induce the enzyme tyrosine aminotransferase (TyrATase) but also inhibits the induction of TyrATase by dexamethasone. Thus CM is an antiglucocorticoid. This is not caused by cell death, because CM is relatively nontoxic up to concentrations of 10 microM. The concentration of CM needed for half maximal inhibition of TyrATase induction is an order of magnitude lower than that predicted from the apparent cell-free affinity of CM for the glucocorticoid receptors of HTC cells, which suggests that the cell-free binding data does not reflect an equilibrium situation. In fact, the reactive alpha-keto mesylate group was intentionally incorporated into cortisol in hopes of obtaining a steroid capable of undergoing irreversible reactions. When HTC cells were preincubated with either CM or the reversible antiglucocorticoid progesterone and then washed to remove free steroid, only the CM-treated cells failed to show subsequent induction of TyrATase by dexamethasone. Furthermore, preincubation of HTC-cell cytosol with CM blocked approximately 75% of the subsequent exchange binding of [3H]dexamethasone to glucocorticoid receptor sites. Thus, the actions of CM in whole and broken cells either require an exceptionally long time for reversal or are not reversible. Together, these results indicate that CM is a unique antagonist and could be an irreversible antiglucocorticoid in vitro.

Animals↗

Bactericidal mechanisms of human breast milk leukocytes.

The functional capacity of human breast milk phagocytes was evaluated with both bactericidal and biochemical assays. Acridine orange was used as a vital stain for bacteria to directly visualize phagocytosis and killing. Bactericidal capabilities were further examined by colony count and chemiluminescent methods. Cytocentrifuged specimens stained for myeloperoxidase exhibited enzyme activity in breast milk leukocytes equal to that of peripheral neutrophils. A radioisotopic assay of hexose monophosphate shunt activity demonstrated metabolic activity in breast milk leukocytes greater than that in peripheral blood neutrophils. However, the chemiluminescent response of breast cells was negligible, apparently the result of quenching secondary to fat present in the milk; preincubation of human blood leukocytes with the fatty layer of breast milk produced similar inhibition in the chemiluminescence assay. By most parameters breast milk phagocytes are at least equal to blood neutrophils.

Colostrum↗