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Biomedical subjects

C Colby

Publications and source records attributed to C Colby.

At least 37 records · Page 2Linked to original sources
PubMed1995

The effect of adaptive mutagenesis on genetic variation at a linked, neutral locus.

Based on recent studies in single-celled organisms, it has been argued that a fitness benefit associated with a mutation will increase the probability of that mutation occurring. This increase is independent of mutation rates at other loci and is called adaptive mutagenesis. We modeled the effect of adaptive mutagenesis on populations of haploid organisms with adaptive mutation rates ranging from 0 to 1 x 10(-5). Allele frequencies at the selected locus and a neutral linked locus were tracked. We also observed the amount of linkage disequilibrium during the selective sweep and the final heterozygosity after the sweep. The presence of adaptive mutagenesis increases the number of genetic backgrounds carrying the new fitter allele, making the outcomes more representative of the population before the selection. Therefore, more neutral genetic variation is preserved in simulations with adaptive mutagenesis than in those without it due to hitchhiking. Since adaptive mutagenesis is time-dependent, it can generate mutants when other mechanisms of mutation cannot. In addition, adaptive mutagenesis has the potential to confound both phylogeny construction and the detection of natural selection from patterns of nucleotide variation.

Adaptation, Physiological↗
PubMed1993

The distribution and spreading of rare variants in the histone multigene family of Drosophila melanogaster.

We surveyed the distribution of rare variant restriction sites within and among histone gene arrays of Drosophila melanogaster using restriction fragment length polymorphism (RFLP) analysis. Seventy-three naturally occurring arrays were digested with restriction enzymes that had no recognition sites in the published histone sequence. Of the arrays surveyed, 68.5% had at least two nonconsensus restriction sites present as indicated by the presence of a small band or bands on the autoradiographs. These bands were almost always the length of a single repeat in the histone multigene family or a multiple of this length. In arrays with more than one band, intensity of the bands almost always decreased with increasing size. This shows that within these arrays variant restriction sites were predominantly located on adjacent repeats. If these bands are caused by spreading of variant sites, as is most likely, then variants spread along the array as an inverse function of distance. Overall, if a sequence spread it had a 92% probability of ending up in its nearest neighbor. This pattern may result from the noncontiguous nature of the histone family.

Animals↗
PubMed1992

Chemosensitivity and breathing pattern regulation of the coatimundi and woodchuck.

An analysis of breathing pattern regulation was carried out on the coatimundi and woodchuck who represent two different volume-time patterns. It was found that the coati, with a short expiratory time as a fraction of total breath time, TE/TTOT, has a greater sensitivity to CO2 as represented by the slope and threshold of its ventilatory response. Breathing air the coati maintains post-inspiratory inspiratory activity (PIIA) of the posterior cricoarytenoid (PCA) through 51% of expiration, while the woodchuck, who is less sensitive to CO2 and has a long TE/TTOT, exhibits no PIIA of the PCA. The woodchuck also has a greater incidence and duration of end-expiratory pauses (or delayed inspiratory onset). The woodchuck does not demonstrate the usual inverse relationship between VT and TE in response to 5% CO2 and does not recruit PIIA of the PCA at this level of CO2. These data confirm the importance of CO2 chemosensitivity in regulation of TE. It is further demonstrated that interspecific differences in chemosensitivity among three mammals of the same size are reflected in regulation of TE but not in inspiratory 'drive' (as indicated by mean inspiratory flow, VT/TI).

Animals↗
PubMed1987

Effects of hypoxia and hypercapnia on VT, f, and VI of nestling and adult bank swallows.

The effects of hypoxia, hypercapnia, and hypoxic hypercapnia on ventilation, and breathing pattern in adult and nestling bank swallows (Riparia riparia) were assessed. The CO2 threshold above which inhaled minute volume (VI) increased significantly in adults and nestlings was 0.045. At each level of fractional concentration of inspired CO2 (FICO2), ventilation in nestlings was lower than that in adults. At a FICO2 of 0.09, VI of adults increased by 284%, whereas VI in nestlings changed 238%. Adult bank swallows also showed a blunted ventilatory response to hypoxia, and the nestling's response was similar to other birds. Adults exhibited greater changes in VI at all levels of hypoxic hypercapnia compared with nestlings. Combined hypoxic and hypercapnic stimuli had an additive effect on ventilation in both groups. Chronic exposure of nestlings to the hypercapnia and hypoxia within burrows seems to significantly alter their ventilatory response to these respiratory stimuli.

Animals↗
PubMed1981

Synthesis of human interferon beta 1 in Escherichia coli infected by a lambda phage recombinant containing a human genomic fragment.

DNA from a human adult was fragmented by partial digestion with restriction endonuclease EcoRI and cloned in lambda Charon 4A. Clone C15, with a human DNA insert of 17 X 10(3) bases, was identified as containing a gene for the fibroblast interferon, interferon beta 1. Restriction mapping shows that this gene, located on a 1840-base EcoRI fragment, is not interrupted by introns. Moreover, we show that this human genomic DNA fragment is able to direct the synthesis of active human interferon beta 1 in Escherichia coli. Interferon activity of up to 7 X 10(6) U/l was recovered from phage lysates by chromatography on Cibacron blue--Sepharose, and had the same immunological properties and species specificity as interferon produced by human fibroblasts.

Adult↗
PubMed1978

A murine cell possessing a dominant mutation affecting the regulation of interferon production: characterization by intraspecific hybrids.

Using intraspecific hybrids, we have demonstrated the dominant nature of two phenotypic markers present in a mutant mouse 3T6 cell line, designated 3T6-VrB2. These are, resistance to virus infection (Vr) and semiconstitutive synthesis of interferon (IFsc). Hybrids were formed by polyethylene glycol-mediated fusion between 3T6-VrB2, or its parent 3T6, and 2TG0-13, a triply marked derivative of mouse 3T3 cells. When tested for the Vr marker, 3T6-VrB2 X 2TG0-13 hybrid clones displayed a level of resistance to virus infection which was equal to or greater than that of 3T6-VrB2. Similarly, when tested for the IFsc marker, these hybrid clones were found to possess the capacity to confer an interferon-induced antiviral state in mouse L929 cells upon cocultivation. By comparison, clones derived from 3T6 X 2TG0-13 fusions produced high levels of virus and failed to confer an interferon-induced antiviral state in L929 cells.

Animals↗
PubMed1978

Murine interferon system regulation: isolation and characterization of a mutant 3T6 cell engaged in the semiconstitutive synthesis of interferon.

We describe the isolation and characterization of a virus-resistant mutant of murine 3T6 cells. The mutant, designated 3T6-VrB2, displays a high degree of resistance to infection by members of the toga-, rhabdo- and picornavirus classes. The level of this resistance to infection is similar to the parent 3T6 pretreated with approximately 100 lU/ml of interferon. Upon co-cultivation of 3T6-VrB2 cells with interferon-sensitive mouse cells, an antiviral state is induced in the latter cells as measured by a reduction of virus yield following infection. The nature of the induction is defined by a series of experiments using anti-mouse interferon antiserum. In the presence of this antiserum, the ability of the mutant to induce an antiviral state in interferon-sensitive mouse cells upon co-cultivation is eliminated. Additionally, growth of the mutant cells in the presence of this antiserum causes a reversal of the virus-resistant phenotype. Our results indicate that 3T6-VrB2 contains a mutation affecting the regulation of the murine interferon system such that the cell is engaged in the semiconstitutive synthesis of interferon.

Cell Line↗
PubMed1978

Interferon-associated, dsRNA-dependent enzyme activities in a mutant 3T6 cell engaged in the semiconstitutive synthesis of interferon.

Cytoplasmic extracts of untreated cultures of a virus-resistant mutant of mouse 3T6 cells, designated 3T6-VrB2, contain two double-stranded, RNA-activated enzyme activities associated with interferon action. These are the synthesis of a low molecular weight oligonucleotide inhibitor of cell-free protein synthesis from ATP, and the phosphorylation of a 67,000 dalton polypeptide by transfer of the gamma phosphate of ATP. Basal levels of both enzyme activities are detectable in extracts of untreated parental 3T6 cells, and are greatly enhanced upon interferon pretreatment. A procedure was developed, using a nonionic detergent to effect cell lysis, which allowed the analysis of the protein kinase activity from as few as 2 x 10(7) cells. Using this procedure, direct proportionalities were demonstrated between the concentration of interferon to which 3T6 cells were exposed, and both the level of protein kinase activity and the magnitude of the antiviral state were established in these cells. Furthermore, untreated cultures of 3T6-VrB2 exhibited both an antiviral state and an intracellular protein kinase activity equal to that of cultures of the parental 3T6 cells pretreated with a single concentration of mouse interferon.

Cell Line↗
PubMed1977

Monitoring of intraoperative heparinization and blood loss following cardiopulmonary bypass surgery.

Two protocols of heparin management during cardiopulmonary bypass were compared to assess the role of the activated clotting time (ACT) in relation to postoperative blood loss. The study was divided into two groups: Group I, the control group, in which 3 mg. of heparin per kilogram was given as the initial dose and maintained at a dose of 1.5 mg. per kilogram every 45 minutes during cardiopulmonary bypass, and Group II, in which the initail dose of heparin was 2 mg. per kilogram and additional dosage were based upon the ACT. We found a striking decrease in postoperative blood loss as well as a decrease in the amount of heparin administered during cardiopulmonary during cardiopulmonary bypass in Group II patients. In addition, less protamine was required to neutralize the heparin in the second group after bypass. Thus, when patients are given too much heparin, as in our control group, the effectiveness of protamine is decreased. We would like to stress the value of the ACT in controlling heparin administration as well as postoperative blood loss in cardiopulmonary bypass surgery.

Blood Coagulation↗
PubMed1975

Phosphorylation but not transport of sugars is enhanced in virus-transformed mouse 3T3 cells.

The transport and phosphorylation of 2-deoxy-D-glucose are separate and sequential events in both normal and virus-transformed 3T3 cells. The apparent enhancement of 2-dOG uptake by 3T3 cells accompanying virus transformation is not due to an effect on the transport process but to enhanced phosphorylation by intracellular kinases. Phosphorylation of 3-O-methyl-D-glucose does not occur in these cells. Both the rate and extent of transport of this glucose analog is the same in normal cells, SV40 virus-transformed cells and sarcoma virus-transformed cells. The appropriateness of using 3-O-MeG for studies of the glucose transport system of animal cells is examined and discussed.

Animals↗
PubMed1975

The effect of serum on the transport and phosphorylation of 2-deoxyglucose by untransformed and transformed mouse 3T3 cells.

Serum starvation of growing and nongrowing (density-inhibited) mouse 3T3 cells resulted in decreased phosphorylation of 2-deoxy--D-glucose, while the time course of transport of this sugar remained unchanged. Serum starvation of SV40 transformed 3T3 cells (SV101) and spontaneously transformed 3T6 cells did not alter either the time course of transport, or phosphorylation of the sugar. Treatment of SV101 cells with 10(-4) M dibutyryl adenosine cyclic 3':5' monophosphate and 10(-3) M theophylline did not restore the capacity to regulate 2-deoxy-D-glucose phosphorylation when these cells were serum deprived. We conclude that serum factors are involved in the modulation of phosphorylation of 2-deoxy-D-glucose in 3T3 cells rather than its transport. This regulation is operative both in growing as well as nongrowing 3T3 cells. In contrast, transformed cells do not respond to this regulation of 2-deoxy-D-glucose phosphorylation.

Biological Transport, Active↗
PubMed1974

Establishment and maintenance of the interferon-induced antiviral state: studies in enucleated cells.

Requirements for the physical presence of the cell's nucleus for the establishment and maintenance of the interferon-induced antiviral state were investigated. Enucleated chicken embryo fibroblasts were obtained by cytochalasin B treatment during centrifugation. The inhibition of vaccinia virus cytoplasmic DNA synthesis, monitored by autoradiography, was used to measure the antiviral activity resulting from interferon treatment. The antiviral state is not established in cells treated with interferon after removal of their nuclei. On the other hand, cells first treated with interferon for 6 or 12 h and then enucleated express the antiviral state. Furthermore, the antiviral state is maintained in enucleated cells for 16 h after enucleation. The antiviral state appears to be more stable in enucleates than in the residual nucleated cells found in the same cultures. Single cells of antiviral populations are found to be either fully permissive or fully restrictive to vaccinia DNA synthesis. The effect of an increasing intracellular multiplicity of infectious virus is to overcome the antiviral cell's block against viral DNA synthesis.

Animals↗
PubMed1973

SV40 virus transformation of mouse 3T3 cells does not specifically enhance sugar transport.

The apparent enhancement of 2-deoxy-D-glucose uptake by mouse 3T3 cells accompanying transformation by SV40 virus is not due primarily to an effect on the transport process but to enhanced phosphorylation of the sugar by intracellular kinases. Moreover, the effect is not specifically a function of the presence of the viral genome, but is a reflection of the overall growth rate and physiological state of the cell.

Animals↗
PubMed1972

Inhibition of early vaccinia virus ribonucleic acid synthesis in interferon-treated chicken embryo fibroblasts.

Pretreatment of chicken embryo cells with homologous but not heterologous interferon inhibits the synthesis of vaccinia virus early messenger ribonucleic acid (mRNA). This inhibition is seen in the presence of cycloheximide, i.e., in the absence of protein synthesis, suggesting that the virion-bound transcriptase may be the target of the antiviral activity associated with interferon treatment. The inhibition of viral mRNA synthesis is dependent on the amount of chicken interferon used. The nonviral interferon inducer, polyriboinosine.polyribocytidine, similarly inhibits viral early mRNA synthesis in a dose-specific manner. The helical polynucleotide polydeoxyinosine.polyribocytidine, which is not an effective interferon inducer in chicken embryo cells, has no effect on viral ribonucleic acid synthesis.

Animals↗