The Friend spleen focus-forming virus (SFFV) genome: fractionation and analysis of SFFV and helper virus-related sequences.
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Biomedical subjects
Publications and source records attributed to A Bernstein.
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Two quantitative indices of heart rate variability are proposed. Instantaneous variability is defined as the average of the absolute value of instantaneous rate differences over a 30 second interval. It is sensitive to short-term variability changes. Bandwidth variability is defined as twice the standard deviation of instantaneous heart rates over a 30 second interval, and it is a measure of long-term variability. The rationale for the choice of these indices is discussed, and they are compared with other published indices of variability. Samples of computer printout of instantaneous and bandwidth variability obtained from fetal heart rate records are given.
Early transport changes occurring during Friend erythroleukemic cell differentiation are reported. A decrease in the rate of 86Rb transport was observed beginning approximately five hours after stimulation with 1.5% dimethylsulfoxide (DMSO), a potent inducer of Friend cell differentiation. By 12 to 14 hours after DMSO addition, the transport rate had stabilized at close to 60% of control level. This decrease in the rate of 86Rb transport preceded a previously reported decrease in cell volume. Other chemical inducers of Friend cells, such as hypoxanthine and ouabain, also caused early decreases in 86Rb influx. In contrast, xanthine, which does not induce Friend cell differentiation, also did not affect 86Rb influx. The transport of two amino acid analogues, alpha-aminoisobutyric acid and 2-aminobicyclo [2,2,1]-heptane-2-carboxylic acid, which differ in their mode of uptake, was also measured following induction by DMSO. The transport rates of both compounds decreased after a 12-hour exposure to DMSO. In contrast, the uptake of 3H-colchicine, a drug which diffuses passively across the cell membrane, was not significantly affected. Studies with several variant cell lines which do not synthesize hemoglobin in response to DMSO indicate that these non-inducible cells can be divided into two classes--those that demonstrate early changes in transport very similar to the changes observed in inducible cell lines and those which exhibit only small changes in transport. Results obtained using a revertant clone have helped to distinguish between those transport changes which are associated with the induction of hemoglobin synthesis and those which are not. In addition, these early transport changes may be useful in defining the stage in the differentiation process at which a particular variant line is blocked.
Treatment of Friend erythroleukemia cells with several different chemical agents causes an early decrease in the 86Rb+ influx mediated by Na+/K+ adenosine triphosphatase (ATPase). These agents, which induce Friend cells to differentiate, include dimethylsulfoxide (DMSO), ouabain, hypoxanthine, and actinomycin D. The magnitude of the early decrease in 86Rb+ influx correlates with the proportion of cells in cultures of inducible Friend cell clones which later go on to synthesize hemoglobin. Compounds which do not incude differentiation in these cells, such as xanthine, exogenous hematin, and erythropoietin, do not cause a change in 86Rb+ influx. A change in the intracellular K+ ion concentration does not occur during induction by DMSO because, although there is a decrease in K+ content per cell soon after induction, there is a parallel decrease in cell volume. These results and previous observations from this laboratory are discussed in terms of the posible involvement of the Na+/K+ ATPase in Friend cell differentiation.
Daunomycin was coupled to dextrans of various molecular sizes. The binding to the dextran carriers augmented the therapeutic efficacy of the antitumor agent in a murine lymphoma line (YAC). When the treatment with the drug or its conjugates was given concomitantly with the tumor cells at separate sites, the unbound drug was able, at its optimally effective doses, to prevent tumors in 40% of the mice, whereas the drug-dextran was efficient in 80% of the mice. The advantage of the drug-dextran over the free drug was also manifested when the treatment was given 6 days after tumor transplantation. However, a further delay of the treatment resulted in a decrease in the potency of the drug-dextran. Similar behavior was observed when increasing tumor loads were transplanted (10(5)-10(8) cells) and when the treatment was administered immediately. The most favorable effect of the drug-dextran was obtained with 10(7) cells, but against 10(8) cells neither the free drug nor the bound one was effective.
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Production of antibodies was stimulated or suppressed arbitrarily by antigen treatment in vitro of spleens cultured at various time intervals after in vivo immunization. Spleens of mice immunized to the 2,4-dinitrophenyl or (4-hydroxy-3-iodo-5-nitrophenyl)acetyl haptenic determinants produced antibodies in culture when no antigen was applied in vitro. When a conjugate of the hapten to the same carrier employed for priming was given in vitro, an initial reduction of the response was observed, the level of which was dependent on antigen dose. Subsequently, increased amounts of antibodies were measured. In contrast, in vitro exposure to the hapten conjugated to an unrelated carrier resulted in significant reduction of the response for the entire period of the test. This suppressive effect manifested with various carrier proteins (ovalbumin, bovin IgG, bovine and rabbit serum albumin and keyhole limpet hemocyanin), when when applied to cultures in doses which were potentially immunogenic.
Friend erythroleukemic cells (FLC) can be induced to differentiate in vitro by addition of dimethylsulfoxide (DMSO). We have studied the kinetics of induction by measuring cell volume, volume coefficient of variation and cell doubling time. Two distinct volume changes (early and late) are observed after the addition of the inducing agent. The early change occurs after ten hours and consist of a 10-20% decrease in volume compared to an untreated control population. This shift persists for two days and its magnitude is proportional to both the concentration of DMSO and the number of differentiated cells seen on day 5. FLC lines which induce weakly or not all with DMSO exhibit a reduced or absent early volume shift. Inclusion of a local anaesthetic in the culture prevents the appearance of differentiated cells and also counteracts the early volume shift. The exact time of the early volume change is a function of cell growth rate and appears to be cell cycle related. Synchronized cell populations exposed to DMSO during G2 and S phase undergo one round of mitosis before expression of the volume change whereas cells in G2-M express the change only after a second mitosis. A later, more gradual decrease in volume is observed in those cultures which begin to produce hemoglobin. It occurs after approximately five doubling times and coincides with the first appearance of hemoglobin-containing cells. Volume distribution parameters indicate that only a proportion of the population becomes smaller in size.
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College students rated protagonists of vignettes involved in extra-marital affairs in two separate studies. In the first study, where the affair resulted in the errant spouse falling in love, both the husband and wife were perceived more favorably when they cheated than when they were being cheated. The results of the second study, where the affair did not involve love, were opposite from those of the first. The cheating spouse was viewed negatively. No significant differences were found between married and unmarried subjects' perceptions. Results indicated that the motivation for an extramarital affair may be crucial in evaluation. Implications of perceived competence of the spouse were considered.
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A new fetal parameter, the arterial pulse time, is described. It is the time from the onset of the fetal electrocardiographic recording to the arrival of the arterial pulse wave recorded at the fetal head. Since arterial pulse time differs from the pre-ejection period by only an apparently constant value, it is proposed as a potential method for obtaining the pre-ejection period during labor.
A patient is presented who was found to have invasive squamous cell carcinoma arising in the epithelial lining of a lateral cervical cyst which had been present for more than 40 years. Radical neck dissection was performed, and metastases were found in a single cervical lymph node. A critical review of cases of branchiogenic carcinoma reported over the past quarter-century yielded no more than three others which meet the criteria for diagnosis of this entity established by Martin, Morfit, and Ehrlich in 1950.
A chromosomally stable mouse-Chinese hamster hybrid cell line was subjected to five rounds of selection with cytotoxic antisera raised in rabbits against either the parental mouse 3T3 cells or the parental Chinese hamster Wg-1 cells. Routine karyological analysis of clones isolated at each stage of serum selection revealed that treatment with either serum resulted in a limited loss of chromosomes (compared to the untreated hybrid cell cultured in parallel) and that the pattern of chromosome loss could not be correlated with the particular antiserum used for selection. However, more detailed analysis with the SSC-formamide C-banding technique, which identifies chromosomes containing a mouse centromere region, demonstrated that while large-scale chromosome loss was not achieved as a result of antiserum selection, the limited loss of chromosomes did, in fact, reflect a specific depletion of chromosomes in response to treatment with cytotoxic antiserum. Specific chromosomal elimination was shown to occur as early as the first round of antiserum treatment. Antigenic analysis of the serum-selected clones revealed a quantitative decrease in the expression of the species-specific surface antigens selected against, but no qualitative loss of antigens was detected. The results suggest that treatment with cytotoxic antiserum may select for clones that have lost specific chromosomes bearing genes regulating the expression of species-specific surface antigens, rather than for those demonstrating large-scale depletion of chromosomes bearing the corresponding structural genes. Some of these chromosomally depleted hybrid cell clones have been used (along with pseudotype viruses containing the genome of vesicular stomatitis virus within the envelope of murine leukemia virus, VSV [MuLV]), to study the mechanisms regulating MuLV replication in Chinese hamster cells. The results indicate that the restriction of MuLV replication in Chinese hamster cells operates at two levels: (a) an inability to adsorb to or penetrate Chinese hamster cells; and (b) an additional intracellular block which is dominant in the mouse-Chinese hamster hybrid cell clones examined. This latter block is presently under study.
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