Cytokines as potential mediators of acute allograft diastolic dysfunction in cyclosporine-treated patients: a pilot study using in situ hybridization.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
F Johnson
Publications and source records attributed to F Johnson.
Translesional synthesis on DNA templates containing 8-oxo-7,8-dihydrodeoxyadenosine.
This study was designed to establish the miscoding potential of 8-oxo-7,8-dihydrodeoxyadenosine (8-oxo-dA). Oligodeoxynucleotides modified site-specifically with 8-oxo-dA were used as templates in primer extension reactions catalyzed by DNA polymerase I (Klenow fragment), DNA polymerase alpha (pol alpha), or DNA polymerase beta (pol beta). dTMP or dGMP is incorporated opposite 8-oxo-dA when either of these dNTPs is provided as substrate for DNA polymerase. dTMP is incorporated exclusively opposite 8-oxo-dA when all four dNTPs are present in the reaction mixture at equimolar concentrations. Chain extension is catalyzed efficiently by Klenow fragment and pol beta under conditions where 8-oxo-dA is paired with dT at the 3' terminus of the primed DNA template. Chain extension catalyzed by pol alpha proceeds more slowly. As shown by steady-state kinetic experiments, incorporation of dGMP is higher in reactions catalyzed by pol beta than by Klenow fragment or pol alpha. The dG-8-oxo-dA pair is extended efficiently from the 3' terminus in the absence of dTTP. We conclude that DNA containing 8-oxo-dA is capable of miscoding; however, unlike 8-oxo-dG, the mutagenic potential of this lesion is limited.
Base Sequence↗
Hormone-induced changes in identified cell populations of the higher vocal center in male canaries.
Male canaries revise their vocal repertoire every year. Early work indicated that the volume and neuron number of the song-control nucleus HVC (Higher Vocal Center) declined in late-summer/fall as birds added and deleted syllables from their repertoire, and increased in spring as the set of song syllables stabilized to a fixed number. Seasonal variation in serum testosterone levels suggested that these changes in brain and behavior were regulated by testosterone (T). However, although initial studies describing growth and regression of HVC used Nissl-staining to define its borders, recent experiments that have measured the distribution of identified populations of HVC cells (projection neurons, hormone target cells) suggest that there are no seasonal changes in HVC volume or neuron number. In order to clarify the role of T in the regulation of HVC morphology, we castrated male canaries, maintained them on short (fall-like) days, and treated them with either T, antisteroid drugs, or nothing. After 1 month of treatment, we used a double-labeling technique to characterize HVC projection neurons and androgen target cells. The results showed that hormonal manipulation influenced HVC volume, the density and size of HVC cells, and the absolute number and percentage of androgen target cells in HVC. Hormonal manipulation did not influence the absolute number of cells in HVC. Moreover, the distribution of projection neurons, androgen target cells, and the Nissl-defined borders of HVC were closely aligned in all experimental groups, indicating that exposure to T and/or its metabolites (estradiol and dihydrotestosterone) regulates the overall size of HVC by affecting the distributions of both projection neurons and androgen target cells. Analysis of double-labeling results suggests that T specifically influences both cell size and the ability to accumulate androgen among HVC neurons that project to the robust nucleus of the archistriatum (RA). The results of this study show that steroid hormones exert potent effects on HVC morphology in male canaries, but differences between our results and studies of seasonal males suggest there may be additional factors that can regulate HVC morphology.
Animals↗
Neurogenesis in adult canary telencephalon is independent of gonadal hormone levels.
Neurons generated in adulthood are found throughout the canary telencephalon. We are interested in the factors that control the rate of proliferation of stem cells that give rise to these new neurons. The rate of incorporation of newly generated neurons into vocal-control regions varies seasonally. This difference could reflect a higher rate of neurogenesis, a lower rate of cell death, or an altered migration. We examined the incidence of thymidine-labeled cells in the telencephalic ventricular zone of adult canaries as a function of variations in gonadal hormone levels. Adult female canaries maintained on a short-day photoperiod were anesthetized and gonadectomized. Four separate groups of birds received systemic exposure to either testosterone, estradiol, a combination of an anti-androgen and an inhibitor of estrogen synthesis, or nothing. All birds were also implanted with an osmotic minipump that released 3H-thymidine for 3 d and were killed 4 or 7 d following the onset of treatment. Analysis of autoradiograms revealed no differences between groups in the incidence of labeling within the ventricular zone either at the level of the anterior commissure or directly adjacent to the vocal-control nucleus HVC (higher vocal center). These results suggest that sex steroids do not regulate the rate of cell division in the ventricular zone. Seasonal differences in the incorporation of labeled cells into HVC may therefore be due to regulation of neurogenesis by photoperiodic factors other than gonadal steroids or to some other cellular mechanism, such as differential migration or survival of neurons.
Animals↗
Induced cell death in a thalamic nucleus during a restricted period of zebra finch vocal development.
A discrete network of forebrain nuclei underlies vocal learning and production in male zebra finches. Three nuclei within this network form a neural pathway that is particularly important for vocal learning in juveniles: area X of the avian striatum projects to the medial dorsolateral nucleus of the anterior thalamus (DLM), which in turn projects to the lateral magnocellular nucleus of the anterior neostriatum (IMAN). Lesions of any of these nuclei in juvenile birds disrupt normal vocal development, whereas the same lesions in adult birds have no effect on already-learned song. Because numerous studies have shown that neuronal survival in the developing nervous system depends on access to efferent targets, we have investigated the possibility that the survival of DLM neurons is similarly regulated over the course of vocal learning. Thus, the efferent target of DLM (IMAN) was lesioned electrolytically in male birds at various stages of vocal development (20, 40, 60 d of age and adult) and birds were killed either 2, 4, or 6 d postlesion. Electrolytic lesions of IMAN removed the single identified efferent target of DLM projection neurons and axotomized the terminal arborizations of these neurons. Although DLM does not normally lose neurons during vocal development, IMAN lesions in 20-d-old birds yielded numerous pyknotic cells throughout DLM by 4 d postlesion and a two-thirds reduction in DLM neuron density by 6 d postlesion. In contrast, IMAN lesions in adult birds had little or no effect on neuronal survival in DLM. Analysis of 40-d-old birds revealed significant but less substantial cell loss than in 20-d-old birds, whereas 60-d-old birds were not different from adults. The age-related decline in the vulnerability of DLM cells to IMAN lesion-induced death suggests that factors that regulate DLM neuron survival may also be involved in the acquisition of learned vocal behavior in songbirds.
Aging↗
Growth and regression of thalamic efferents in the song-control system of male zebra finches.
A serial forebrain pathway in the songbird brain plays a critical role in vocal learning; Area X of the parolfactory lobe (X) projects to the medial portion of the dorsolateral nucleus of the anterior thalamus (DLM), which in turn projects to the lateral magnocellular nucleus of the anterior neostriatum (IMAN). Lesions of this pathway in juvenile birds disrupt vocal development, whereas identical lesions in adult birds do not influence the production of already learned song. During the course of vocal learning, IMAN undergoes a phase of massive neuronal loss, whereas the neuronal population of X more than doubles. In the present study, the development of neuron number in DLM was analyzed and found not to change during the course of vocal learning. Anterograde DiI labeling of DLM efferent fibers was then used to analyze the morphological development of this projection in relation to both the loss of neurons from lMAN and the loss of the ability of X-DLM-lMAN lesions to influence vocal production. We found that DLM axons arrive within lMAN by 15 days of age, prior to both the loss of neurons from lMAN and the onset of vocal production. The volume of anterograde DiI label over lMAN did not change between 15 and 20 days of age, but this volume more than doubled between 20 and 35 days of age. During this phase of exuberant growth, anterograde label matched the dorsal border of lMAN but extended beyond all other borders of lMAN into a surrounding "shell" of parvicellular neurons.(ABSTRACT TRUNCATED AT 250 WORDS)
Afferent Pathways↗
Influence of an exocyclic guanine adduct on the thermal stability, conformation, and melting thermodynamics of a DNA duplex.
As part of an overall program to characterize the impact of mutagenic lesions on the physiochemical properties of DNA, we report here the results of a comparative spectroscopic study on pairs of DNA duplexes both with and without an exocyclic guanine lesion. Specifically, we have studied a family of four 13-mer duplexes of the form d(CGCATGYGTACGC).d(GCGTACZCATGCG) in which Y is either the normal deoxyguanosine residue (G) or the exocyclic guanine adduct 1,N2-propanodeoxyguanosine (X), while Z is either deoxycytosine (C) or deoxyadenosine (A). Thus, the four duplexes studied, which can be designated by the identity of their central Y.Z base pair, are a Watson-Crick duplex (GC), a duplex with a central mismatch (GA), and two duplexes with exocyclic guanine lesions (X), that differ only by the base opposite the lesion (XC and XA). The data derived from our spectroscopic measurements on these four duplexes have allowed us to evaluate the influence of the exocyclic guanine lesion, as well as the base opposite the lesion, on the conformation, thermal stability, and melting energetics of the host DNA duplex. To be specific, our circular dichroism (CD) spectra show that the exocyclic guanine lesion induces alterations in the duplex structure, while our temperature-dependent optical measurements reveal that these lesion-induced structural alterations reduce the thermal stability, the transition enthalpy, and the transition free energy of the duplex.(ABSTRACT TRUNCATED AT 250 WORDS)
Base Sequence↗
Matters of life and death in the songbird forebrain.
Male zebra finches learn a specific vocal pattern during a restricted period of development. They produce that song in stereotyped form throughout adulthood, and are unable to learn new song patterns. Development of the neural substrate for song learning and behavior is delayed relative to other brain regions, and neural song-control circuits undergo dramatic changes during the period of vocal learning due to both loss of neurons as well as incorporation of newly generated neurons. In contrast, canaries do learn new song patterns in adulthood and modify their vocal repertoires each breeding season. Adult canaries also maintain a large population of dividing cells in the ependymal zone of the telencephalon, and vast numbers of newly generated neurons migrate out to become incorporated into functional circuits and replace older neurons. We review the relationships between cellular and behavioral aspects of song learning in both zebra finches and canaries, as well as the role of gonadal hormones in regulating diverse aspects of the song-control system.
Animals↗
Transcutaneous optical telemetry system for an implantable electrical ventricular heart assist device.
Explore the source record for details and available documents.
Heart-Assist Devices↗
Lipreading in patients with schizophrenia.
This study was designed to explore whether schizophrenic patients who are able to maintain their gaze with adequate persistence could competently lip-read. Four lipreading tests, designed to assess recognition of syllables, words, and overlearned sentences, were administered to 15 schizophrenic and 15 normal subjects matched for age, sex, and educational level. The patients proved to be competent lip-readers susceptible to the blend illusion and were inferior only in lipreading of overlearned sentences. The latter difficulty may tentatively be attributed to the inadequacy of the patient's premorbid social network for establishing contextual cues that aid in the recognition of overlearned sentences.
Adult↗
Acute toxic delirium in a patient using transdermal fentanyl.
Explore the source record for details and available documents.
Acute Disease↗
Local distribution and dosimetry of 226Ra in the trabecular skeleton of the beagle.
Young adult beagle dogs received a single injection of 38.1 kBq/kg body wt 226Ra and were serially sacrificed at 4 to 2955 days postinjection. Samples of sites of trabecular bone in the lumbar vertebral body, proximal ulna, and distal femoral metaphysis and epiphysis were analyzed autoradiographically. The time-dependent changes in the average 226Ra concentrations in the four regions were analyzed in terms of a compartmental model. The clearance rate from the lumbar vertebral body was about four times more rapid than for the proximal ulna and distal femoral epiphysis. Ratios of hotspot to diffuse label concentrations varied from about 10 to 23. The dose rate to the endosteum ranged between 8.7 and 39.5 mGy/day initially and 4 and 10.5 mGy/day toward the end of the observation period. Mean marrow dose rates were lower by a factor of 3 to 9.5. During their residence time the nuclei of bone lining cells receive a maximum dose of 8 Gy in the proximal ulna (2955 days after injection) and a minimum dose of 0.63 Gy in the lumbar vertebra (2955 days after injection). This corresponds on the average to 17 and 1.4 alpha-particle hits to the cell nuclei, respectively.
Animals↗
Inhibition of cellular thymidylate synthesis by cytotoxic propenal derivatives of pyrimidine bases and deoxynucleosides.
A series of cytotoxic propenal (3-oxoprop-1-enyl) derivatives of pyrimidine bases and deoxynucleosides was evaluated for their ability to block thymidylate synthesis in intact and permeabilized murine leukemia L1210 cells. Several were potent inhibitors of this process, likely contributing to their cytotoxicity. The IC50 values of thymidine-3-propenal, the prototype of this series, in intact and permeabilized L1210, L-M and L-M(TK-) cells were 21, 7.5, and 75 microM and 1.5, 1.7, and 3.5 microM, respectively. The related base analogue, thymine-1-propenal, is a product of bleomycin-induced DNA strand-scission; the results of the present study bear on the mode of action of this antibiotic.
Acrolein↗
Structural features of an exocyclic adduct positioned opposite an abasic site in a DNA duplex.
Structural studies have been extended to dual lesions where an exocyclic adduct is positioned opposite an abasic site in the center of a DNA oligomer duplex. NMR and energy minimization studies were performed on the 1,N2-propanodeoxyguanosine exocyclic adduct (X) positioned opposite a tetrahydrofuran abasic site (F) with the dual lesions located in the center of the (C1-A2-T3-G4-X5-G6-T7-A8-C9).(G10-T11-A12-C-13-F14-C15 -A16-T17-G-18) X.F 9-mer duplex. Two-dimensional NMR experiments establish that the X.F 9-mer helix is right-handed with Watson-Crick A.T and G.C base pairing on either side of the lesion site. NOEs are detected from the methylene protons of the exocyclic ring of X5 to the imino protons of G4.C15 and G6.C13 which flank the lesion site, as well as to the H1' and H1" protons of the cross strand F14 tetrahydrofuran moiety. These NMR results establish that the exocyclic adduct X5 is positioned between flanking G4.C15 and G6.C13 base pairs and directed toward the abasic lesion F14 on the partner strand. These studies establish that the exocyclic ring of the 1,N2-propanodeoxyguanosine adduct fits into the cavity generated by the abasic site.
Base Composition↗
NMR structural studies of the ionizing radiation adduct 7-hydro-8-oxodeoxyguanosine (8-oxo-7H-dG) opposite deoxyadenosine in a DNA duplex. 8-Oxo-7H-dG(syn).dA(anti) alignment at lesion site.
Proton NMR studies are reported on the complementary d(C1-C2-A3-C4-T5-A6-oxo-G7-T8-C9-A10-C11-C12).d(G13-G14-T15- G16-A17-A18-T19- A20-G21-T22-G23-G24) dodecanucleotide duplex (designated 8-oxo-7H-dG.dA 12-mer), which contains a centrally located 7-hydro-8-oxodeoxyguanosine (8-oxo-7H-dG) residue, a group commonly found in DNA that has been exposed to ionizing radiation or oxidizing free radicals. From the NMR spectra it can be deduced that this moiety exists as two tautomers, or gives rise to two DNA conformations, that are in equilibrium and that exchange slowly. The present study focuses on the major component of the equilibrium that originates in the 6,8-dioxo tautomer of 8-oxo-7H-dG. We have assigned the exchangeable NH1, NH7, and NH2-2 base protons located on the Watson-Crick and Hoogsteen edges of 8-oxo-7H-dG7 in the 8-oxo-7H-dG.dA 12-mer duplex, using an analysis of one- and two-dimensional nuclear Overhauser enhancement (NOE) data in H2O solution. The observed NOEs derived from the NH7 proton of 8-oxo-7H-dG7 to the H2 and NH2-6 protons of dA18 establish an 8-oxo-7H-dG7(syn).dA 18(anti) alignment at the lesion site in the 8-oxo-7H-dG.dA 12-mer duplex in solution. This alignment, which places the 8-oxo group in the minor groove, was further characterized by an analysis of the NOESY spectrum of the 8-oxo-7H-dG.dA 12-mer duplex in D2O solution. We were able to detect a set of intra- and interstrand NOEs between protons (exchangeable and nonexchangeable) on adjacent residues in the d(A6-oxo-G7-T8).d(A17-A18-T19) trinucleotide segment centered about the lesion site that establishes stacking of the oxo-dG7(syn).dA(anti) pair between stable Watson-Crick dA6.dT19 and dT8.dA17 base pairs with minimal perturbation of the helix. Thus, both strands of the 8-oxo-7H-dG.dA 12-mer duplex adopt right-handed conformations at and adjacent to the lesion site, the unmodified bases adopt anti glycosidic torsion angles, and the bases are stacked into the helix. The energy-minimized conformation of the central d(A6-oxo-G7-T8).d(A17-A18-T19) segment requires that the 8-oxo-7H-dG7(syn).dA18(anti) alignment be stabilized by two hydrogen bonds from NH7 and O6 of 8-oxo-7H-dG7(syn) to N1 and NH2-6 of dA18(anti), respectively, at the lesion site.(ABSTRACT TRUNCATED AT 400 WORDS)
8-Hydroxy-2'-Deoxyguanosine↗
Environmental and biological incidences over predatory aggression in rodents.
Explore the source record for details and available documents.
Aggression↗
Site-specific mutagenesis using a gapped duplex vector: a study of translesion synthesis past 8-oxodeoxyguanosine in E. coli.
We have constructed a gapped plasmid vector in which a single defined lesion is introduced, site-specifically, within a single-strand region. Efficiency of translesional synthesis is determined by the number of colonies recovered following transformation of E. coli. The nucleotide sequence of progeny plasmids in the gapped region of the vector reflects incorporation of bases opposite and near the lesion. The analysis detects non-mutagenic as well as mutagenic events. This system was used to establish the mutagenic potential of 2'-deoxy-7,8-dihydro-8-oxoguanosine (8-oxodG), a lesion produced by the action of active oxygen species on DNA. The presence of 8-oxodG did not affect the number of transformants recovered. Most transformants (greater than 99%) contained G:C pairs at the site of the lesion; however, a limited number of targeted G----T transversions were observed in the presence and absence of SOS induction. Base substitutions neighboring the lesion, reported for an in vitro system, were not observed. We conclude that the 8-oxodG lesion in DNA is weakly mutagenic in E. coli.
8-Hydroxy-2'-Deoxyguanosine↗
Rupture of arteriovenous fistula after in situ saphenous vein bypass.
Residual saphenous vein tributaries function as arteriovenous fistulas after in-situ lower extremity bypass. Whether or not all of these tributaries need to be ligated at the time of bypass is controversial since many will close spontaneously. Other consequences of retained fistulas range from local skin problems to diminished graft flow and ultimate graft thrombosis. A complication not previously reported is rupture of a retained arteriovenous fistula. This unusual and potentially catastrophic complication should be discoverable at an earlier stage by periodic graft surveillance by means of duplex sonography. The routine policy of selective ligation of saphenous vein tributaries needs to be reexamined.
Aged↗