Biomedical subjects

S C Christensen

Publications and source records attributed to S C Christensen.

At least 19 recordsLinked to original sources

PubMed1997

Identification of quantitative trait loci involved in contextual and auditory-cued fear conditioning in BXD recombinant inbred strains.

Fear conditioning shows associations formed between contextual or auditory stimuli with an unconditioned stimulus. Inbred mouse strains differ in their ability to demonstrate fear conditioning, suggesting at least a partial genetic influence. The present study identified the possible chromosomal loci regulating fear conditioning in BXD recombinant inbred strains using quantitative trait loci (QTL) analysis. Estimates of heritability for all 3 measures of conditioning were about .28. Correlational analyses between genetic markers and strain means identified multiple putative QTLs. The strongest associations were on Chromosomes 1 and 17 for freezing to the context, Chromosome 12 for freezing to an altered context, and Chromosome 1 for freezing to the auditory stimulus. Overlapping QTLs may indicate some common genes that underlie aspects of this learning task.

Animals↗

PubMed1997

Quantitative trait locus analysis of contextual fear conditioning in mice.

Family, twin and adoption studies provide evidence for a substantial genetic component underlying individual differences in general intelligence, specific cognitive abilities and susceptibility to psychopathologies related to fear-inducing events. Contextual fear conditioning, which is highly conserved across species, can serve as a model for elucidating genes that regulate individual differences in learning and emotion. In fear conditioning, an initially neutral stimulus, such as a tone or a particular environment (context), elicits a fear response after it has been paired with an aversive stimulus, such as shock. Two neural circuits have been implicated in fear conditioning. The fear component is regulated by amygdaloid pathways, while the contextual component is, at least in part, dependent on the hippocampus. C57BL/6J (B6) and DBA/2J (D2) mice differ in several types of complex learning. including contextual fear conditioning. A quantitative trait locus (QTL) analysis of contextual fear conditioning was performed in a B6/D2 F2 intercross population. Two QTLs for contextual conditioning (lod score > 4.3) were identified on chromosomes 10 and 16. QTLs for conditioning to the auditory cue (lod score > 4.3) were localized to chromosomes 1 and 10. Suggestive QTLs (lod score = 2.8-4.1) for contextual conditioning were detected on chromosomes 1, 2 and 3.

Animals↗

PubMed1996

Quantitative trait locus analyses of sleep-times induced by sedative-hypnotics in LSXSS recombinant inbred strains of mice.

The long-sleep (LS) and short-sleep (SS) selected lines of mice show highly significant differences in sleep-time for many sedative-hypnotic drugs, and the quantitative genetic nature of these differences has been well-established. Using an interval-mapping approach, quantitative trait locus (QTL) analyses of LSXSS recombinant inbred (RI) strains have been applied to sleep-time responses for various classes of sedative-hypnotic drugs: alcohols (ethanol, n-propanol, and n-butanol), the atypical anesthetic chloral hydrate, barbiturates (pentobarbital and secobarbital), and benzodiazepines (chlordiazepoxide and flurazepam). Several provisional QTLs were mapped to similar locations within and between drug classes, suggesting that some common loci are involved in sleep-times elicited by these drugs. Consistent with correlations of strain mean sleep-times between drugs tested in the LSXSS recombinant inbred strains, the number of provisional QTLs mapping to the locations of highest significance for ethanol decreases when the lipid solubility of a particular drug becomes less similar to that of ethanol. Provisional QTLs mapped for the benzodiazepines, however, revealed considerable overlap with those mapped for ethanol, although these drugs represented the most lipid-soluble category of sedative-hypnotics tested. Provisional QTLs for pentobarbital and secobarbital differed from most of those mapped for the alcohols, which supports the hypothesis that alcohols and barbiturates exert their effects mainly through different biological mechanisms in the LS and SS lines. Blood ethanol concentrations at regaining the righting reflex also mapped to several provisional QTLs corresponding to ethanol-induced sleep-times that support the contention that sleep-time is a reasonable index of the observed differences in central nervous system sensitivities to ethanol between LS and SS mice.

1-Butanol↗

PubMed1995

Protein and molecular characterization of hippocampal protein kinase C in C57BL/6 and DBA/2 mice.

Measures of protein kinase C (PKC) in C57BL/6 and DBA/2 mice using [3H]phorbol 12,13-dibutyrate binding to tissue homogenates and brain slices demonstrated that levels of activated, membrane-bound PKC were greater in C57BL hippocampus than in DBA hippocampus. Western analysis of alpha-, beta I-, beta II-, gamma-, delta-, and epsilon-PKC using isozyme-specific antibodies indicated that the increase observed in C57BL hippocampus was due primarily to the gamma-PKC protein, whose immunoreactivity was greater in the membrane-bound fraction in C57BL mice. Characterization of alpha-, beta I,II-, and gamma-PKC hippocampal mRNA using northern analysis and isozyme-specific nucleic acid probes did not reveal differences between the strains in levels of gene expression. Restriction fragment length polymorphisms (RFLP) were found in the alpha- and gamma-, but not beta-PKC genomic DNA. The RFLPs appeared to be located in noncoding, nonregulatory regions of the gene. These findings suggest that the gamma-PKC isozyme is largely responsible for the PKC activity difference in C57BL and DBA hippocampus that has been reported previously and may be closely associated with differences in learning ability observed in these strains.

Animals↗

PubMed1983

Popliteal artery puncture in the assessment of patients with severe leg ischemia.

Two-plane angiography and direct segmental pressure measurements in the femoral and popliteal arteries and indirectly on the arm and ankle were performed in 101 limbs seeking to establish a relationship between angiographic assessment of the patency of the popliteal artery and the trifurcation vessels and the popliteal ankle pressure difference. When the tiberoperoneal trunk or the trifurcation vessels were occluded or more than 50% of the lumen was stenosed, the pressure difference exceeded 10 mmHg in 30/40 limbs (75%). When three, two, or only one of the tibial vessels were patent, the pressure difference exceeded 10 mmHg in 2/58 limbs (3%). One month following above knee femoropopliteal bypass (48 limbs), patients with a popliteal-ankle difference less than 10 mmHg obtained a significantly higher ankle pressure index (PI 0.86, range 0.56-1.20) (p less than 0.01) than those with a pressure difference exceeding 10 mmHg (PI 0.66, range 0.40-0.91). The clinical state 6 months following femoropopliteal bypass did not demonstrate that patients with a low popliteal-ankle difference fared better than patients with a higher pressure difference; however, the PI appeared significantly lower in the latter group compared to the former. The graft material was correlated to the popliteal-ankle pressure difference. It appeared that prosthetic grafts failed within 6 months when the difference exceeded 10 mmHg in 10/12 limbs (83%), but autologous vein grafts only failed in 2/10 limbs (20%). Finally, it was possible to predict the postoperative ankle pressure index significantly from data derived from the pressure measurements.

Adult↗

PubMed1981