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Biomedical subjects

F Johnson

Publications and source records attributed to F Johnson.

At least 73 records · Page 4Linked to original sources

Neurotrophins suppress apoptosis induced by deafferentation of an avian motor-cortical region.

Studies of the developing nervous system led to the general view that growth factors promote neuronal survival in a "retrograde" manner. For example, release of NGF from postsynaptic peripheral targets followed by uptake and retrograde transport by presynaptic neurons provided a widely accepted conceptual framework for the action of neurotrophins. In contrast, although presynaptic or "anterograde" influences on the survival of developing neurons have been recognized for some time, the mechanisms by which afferent input regulates the survival of postsynaptic cells have received considerably less attention. In the forebrain network for learned vocal behavior in zebra finches, lesions of a cortical region for song control, the lateral magnocellular nucleus of the anterior neostriatum (lMAN), remove presynaptic input to a motor-cortical song region, the robust nucleus of the archistriatum (RA), and cause massive RA neuron death in young birds that are entering the sensitive period for song learning. Here we report that lesions of lMAN followed by infusions of neurotrophins directly into RA completely suppress neuronal apoptosis in RA. Moreover, we show that lMAN neurons are able to transport neurotrophins in the anterograde direction to RA, that neurotrophin-like immunoreactivity is present in cells in lMAN and RA, and that neurotrophin receptor-like immunoreactivity is present in RA. Expression of neurotrophins in lMAN and RA suggests that lMAN presynaptic input could regulate RA neuron survival by synthesizing, transporting, and releasing neurotrophins anterogradely or by regulating the auto/paracrine release of neurotrophins within RA, or perhaps by both. These data provide the first in vivo demonstration that neurotrophins can prevent the death of deafferented cortical neurons, and they raise the possibility that nonretrograde signaling by neurotrophins may be a common means of promoting neuronal survival in the vertebrate telencephalon. Anterograde and auto/paracrine neurotrophin signaling, along with the more established view that neurotrophins regulate neuron survival via retrograde mechanisms, suggests multidirectional neurotrophin signaling in the vertebrate telencephalon.

Animals↗

A new method for straightening DNA molecules for optical restriction mapping.

We have developed an improved method of straightening DNA molecules for use in optical restriction mapping. The DNA was straightened on 3-aminopropyltriethoxysilane-coated glass slides using surface tension generated by a moving meniscus. In our method the meniscus motion was controlled mechanically, which provides advantages of speed and uniformity of the straightened molecules. Variation in the affinity of the silanized surfaces for DNA was compensated by precoating the slide with single-stranded non-target blocking DNA. A small amount of MgCl2 added to the DNA suspension increased the DNA-surface affinity and was necessary for efficient restriction enzyme digestion of the straightened surface-bound DNA. By adjusting the amounts of blocking DNA and MgCl2, we prepared slides that contained many straight parallel DNA molecules. Straightened lambda phage DNA (48 kb) bound to a slide surface was digested by EcoRI restriction endonuclease, and the resulting restriction fragments were imaged by fluorescence microscopy using a CCD camera. The observed fragment lengths showed excellent agreement with their predicted lengths.

Bacteriophage lambda↗

Disposable gloves: research findings on use in practice.

This article reviews the research evidence for the safety and effectiveness of disposable gloves in preventing transmission of infection. The author concludes that all nurses should have a glove policy for their unit or department to ensure the correct type of gloves are worn in appropriate situations.

Communicable Disease Control↗

Circuits, hormones, and learning: vocal behavior in songbirds.

Species-typical vocal patterns subserve species identification and communication for individual organisms. Only a few groups of organisms learn the sounds used for vocal communication, including songbirds, humans, and cetaceans. Vocal learning in songbirds has come to serve as a model system for the study of brain-behavior relationships and neural mechanisms of learning and memory. Songbirds learn specific vocal patterns during a sensitive period of development via a complex assortment of neurobehavioral mechanisms. In many species of songbirds, the production of vocal behavior by adult males is used to defend territories and attract females, and both males and females must perceive vocal patterns and respond to them. In both juveniles and adults, specific types of auditory experience are necessary for initial song learning as well as the maintenance of stable song patterns. External sources of experience such as acoustic cues must be integrated with internal regulatory factors such as hormones, neurotransmitters, and cytokines for vocal patterns to be learned and produced. Thus, vocal behavior in songbirds is a culturally acquired trait that is regulated by multiple intrinsic as well as extrinsic factors. Here, we focus on functional relationships between circuitry and behavior in male songbirds. In that context, we consider in particular the influence of sex hormones on vocal behavior and its underlying circuitry, as well as the regulatory and functional mechanisms suggested by morphologic changes in the neural substrate for song control. We describe new data on the architecture of the song system that suggests strong similarities between the songbird vocal control system and neural circuits for memory, cognition, and use-dependent plasticity in the mammalian brain.

Animals↗

Recognition and conversion of single- and double-stranded oligonucleotide substrates by 8-oxoguanine-DNA glycosylase from Escherichia coli.

The substrate specificity of 8-oxoguanine-DNA glycosylase was studied. The data showed for the first time that the enzyme can cleave single-stranded deoxyoligonucleotides containing an 8-oxoG link. The values of K(m) and Vmax for a range of single-stranded and double-stranded oligonucleotides (23 bp) containing 8-oxoG at different positions of one chain. These parameters consistently depended on the position of 8-oxoG in single-stranded or double-stranded substrates. A possible mechanism responsible for substrate recognition by 8-oxoguanine-DNA glycosylase is described.

Base Sequence↗

A case of chrysiasis.

Chrysiasis and chrysoderma are terms used to describe permanent pigmentation of the skin due to the parenteral administration of gold salts. A case of chrysiasis, including a photomicrograph of the characteristic orange-red birefringence of gold in tissue when viewed under cross-polarized light, is presented. A review of the literature on the pathogenesis of the pigmentation seen in this disorder is also presented.

Aged↗

Substrate specificity of Escherichia coli MutY protein.

The MutY protein of Escherichia coli removes mismatched deoxyadenine residues from DNA. In this study, duplex oligodeoxynucleotides containing modified bases are used as model substrates for this enzyme. In contrast to a recent report [Lu, A.-L., et al. (1995) J. Biol. Chem. 270, 23582], dA:8-oxo-dG appears to be the preferred natural substrate for MutY, as evidenced by the specificity constants (kcat/Km) for dA:8-oxo-dG and dA:dG of 39 600 x 10(-6) and 383 x 10(-6) (min-1 nM-1), respectively. kcat for the duplex containing dA:dG was highest at lower pH; the rate of cleavage for the duplex containing dA:8-oxo-dG was unaffected over a pH range of 5.5-8.0. The presence of an 8-oxo function in dG increased significantly the rate of removal of dA from all substrates tested. Replacement of dA by rA reduced the specificity constant of dA:8-oxo-dG to 294 x 10(-6) (min-1 nM-1), whereas replacement of dA by 2'-O-methyladenosine virtually abolished enzymatic activity. Modifications of the dG moiety generally were better tolerated than those of dA; however, introduction of a methyl ether at the 6 position of dG produced a noncleavable substrate and replacement of dG by 2'-O-methylguanosine generated a substrate with a low specificity constant. Rates of cleavage of duplexes containing dA:dC and dA:tetrahydrofuran were three orders of magnitude lower than the reference substrate. Duplexes containing a carbocyclic analog of dA were not cleaved. A model is proposed to explain the recognition of DNA substrates by MutY and the catalytic properties of this enzyme.

DNA↗

The length of the cervix and the risk of spontaneous premature delivery. National Institute of Child Health and Human Development Maternal Fetal Medicine Unit Network.

BACKGROUND: The role of the cervix in the pathogenesis of premature delivery is controversial. In a prospective, multicenter study of pregnant women, we used vaginal ultrasonography to measure the length of the cervix; we also documented the incidence of spontaneous delivery before 35 weeks' gestation. METHODS: At 10 university-affiliated prenatal clinics, we performed vaginal ultrasonography at approximately 24 and 28 weeks of gestation in women with singleton pregnancies. We then assessed the relation between the length of the cervix and the risk of spontaneous preterm delivery. RESULTS: We examined 2915 women at approximately 24 weeks of gestation and 2531 of these women again at approximately 28 weeks. Spontaneous preterm delivery (at less than 35 weeks) occurred in 126 of the women (4.3 percent) examined at 24 weeks. The length of the cervix was normally distributed at 24 and 28 weeks (mean [+/- SD], 35.2 +/- 8.3 mm and 33.7 +/- 8.5 mm, respectively). The relative risk of preterm delivery increased as the length of the cervix decreased. When women with shorter cervixes at 24 weeks were compared with women with values above the 75th percentile, the relative risks of preterm delivery among the women with shorter cervixes were as follows: 1.98 for cervical lengths at or below the 75th percentile (40 mm), 2.35 for lengths at or below the 50th percentile (35 mm), 3.79 for lengths at or below the 25th percentile (30 mm), 6.19 for lengths at or below the 10th percentile (26 mm), 9.49 for lengths at or below the 5th percentile (22 mm), and 13.99 for lengths at or below the 1st percentile (13 mm) (P < 0.001 for values at or below the 50th percentile; P = 0.008 for values at or below the 75th percentile). For the lengths measured at 28 weeks, the corresponding relative risks were 2.80, 3.52, 5.39, 9.57, 13.88, and 24.94 (P < 0.001 for values at or below the 50th percentile; P = 0.003 for values at the 75th percentile). CONCLUSIONS: The risk of spontaneous preterm delivery is increased in women who are found to have a short cervix by vaginal ultrasonography during pregnancy.

Cervix Uteri↗

The preterm prediction study: fetal fibronectin, bacterial vaginosis, and peripartum infection. NICHD Maternal Fetal Medicine Units Network.

OBJECTIVE: To determine the relation between vaginal and upper genital tract infection and cervical-vaginal fetal fibronectin levels. METHODS: We screened 2899 women at ten centers every 2 weeks from 23-24 to 30 weeks' gestation for cervical and vaginal fetal fibronectin. A positive test was defined as a level of at least 50 ng/mL. The relation between a positive test and bacterial vaginosis at 23-24 weeks and clinical or histologic chorioamnionitis at delivery plus neonatal sepsis was determined. RESULTS: Fetal fibronectin was present in 4.0% of cervical and/or vaginal samples at 23-24 weeks and was nearly twice as common in women with bacterial vaginosis. Adjusting for the presence of bacterial vaginosis, race, and parity, women positive for fetal fibronectin were much more likely to have clinical chorioamnionitis (mean +/- standard deviation gestational age 30.6 +/- 4.1 weeks), with an odds ratio of 16.4 and 95% confidence interval of 7.1-37.8, and neonatal sepsis (6.3 and 2.0-20.0, respectively), than those who were fetal fibronectin-negative. A positive cervical fetal fibronectin test was a better predictor of clinical chorioamnionitis and neonatal sepsis than was a vaginal test or a combination of vaginal and cervical tests. Among 40 women who delivered before 32 weeks and had placental histology available for evaluation, ten had a positive cervical and/or vaginal fetal fibronectin test before delivery; all ten had histologic evidence of chorioamnionitis, compared with only 13 of 30 women (43%) who were fetal fibronectin-negative (P = .02). CONCLUSION: Women with bacterial vaginosis were more likely to have a positive fetal fibronectin test than uninfected women. Women with a positive fetal fibronectin test who delivered before 32 weeks' gestation all had evidence of histologic chorioamnionitis. Women positive for fetal fibronectin also had a 16-fold increase in clinical chorioamnionitis and a sixfold increase in neonatal sepsis. There is strong evidence that upper genital tract infection and cervical and/or vaginal fetal fibronectin are closely linked.

Adult↗

The preterm prediction study: maternal stress is associated with spontaneous preterm birth at less than thirty-five weeks' gestation. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.

OBJECTIVE: Our purpose was to determine whether various measures of poor psychosocial status in pregnancy are associated with spontaneous preterm birth, fetal growth restriction, or low birth weight. STUDY DESIGN: Anxiety, stress, self-esteem, mastery, and depression were assessed at 25 to 29 weeks in 2593 gravid women by use of a 28-item Likert scale. Scores for each psychosocial subscale were determined, and an overall psychosocial score was calculated. Scores were divided into quartiles, and the lowest quartile scores were used to define poor psychosocial status. The percent spontaneous preterm birth, low birth weight, and fetal growth restriction in women with low and high psychosocial scores were compared. Logistic regression analyses provided the odds ratios and 95% confidence intervals. RESULTS: Analyses revealed that stress was significantly associated with spontaneous preterm birth and with low birth weight with odds ratios of 1.16, p = 0.003, and 1.08, p = 0.02, respectively, for each point on the scale. A low score on the combined scale or on any subscale other than stress did not predict spontaneous preterm birth, fetal growth restriction, or low birth weight. After multivariate adjustment was performed for psychosocial status, substance use, and demographic traits, black race was the only variable significantly associated with spontaneous preterm birth, fetal growth restriction, and low birth weight; stress and low education were associated with spontaneous preterm birth and low birth weight. CONCLUSION: Stress was associated with spontaneous preterm birth and low birth weight even after adjustment for maternal demographic and behavioral characteristics. Black race continues to be a significant predictor of spontaneous preterm birth, fetal growth restriction, and low birth weight even after adjustment for stress, substance use, and other demographic factors.

Adult↗

The preterm prediction study: a clinical risk assessment system.

OBJECTIVE: Our aims were to develop a risk assessment system for the prediction of spontaneous preterm delivery using clinical information available at 23 to 24 weeks' gestation and to determine the predictive value of such a system. STUDY DESIGN: A total of 2929 women were evaluated between 23 and 24 weeks' gestation at 10 centers. Demographic factors, socioeconomic status, home and work environment, drug and alcohol use, and medical history were evaluated. Information regarding symptoms, cultures, and treatments in the current pregnancy were ascertained. Anthropomorphic and cervical examinations were performed. Univariate analysis and multivariate logistic regression were performed in a random selection, constituting 85% of the study population. The derived risk assessment system was applied to the remaining 15% of the population to evaluate its validity. RESULTS: A total of 10.4% of women were delivered of preterm infants. The multivariate models for spontaneous preterm delivery were highly associated with spontaneous preterm delivery (p < 0.0001). A low body mass index (<19.8) and increasing Bishop scores were significantly associated with spontaneous preterm delivery in nulliparous and multiparous women. Black race, poor social environment, and work during pregnancy were associated with increased risk for nulliparous women. Prior obstetric outcome overshadowed socioeconomic risk factors in multiparous women with a twofold increase in the odds of spontaneous preterm delivery for each prior spontaneous preterm delivery. Current pregnancy symptoms, including vaginal bleeding, symptomatic contractions within 2 weeks, and acute or chronic lung disease were variably associated with spontaneous preterm delivery in nulliparous and multiparous women. When the system was applied to the remainder of the population, women defined to be at high risk for spontaneous preterm delivery (> or = 20% risk) carried a 3.8-fold (nulliparous women) and 3.3-fold (multiparous women) higher risk of spontaneous preterm delivery than those predicted to be at low risk. However, the risk assessment system identified a minority of women who had spontaneous preterm deliveries. The sensitivities were 24.2% and 18.2% and positive predictive values were 28.6% and 33.3%, respectively, for nulliparous and multiparous women. CONCLUSIONS: Although it is possible to develop a graded risk assessment system that includes factors that are highly associated with spontaneous preterm delivery in nulliparous and multiparous women, such a system does not identify most women who subsequently have a spontaneous preterm delivery. This system has investigational value as the basis for evaluating new technologies designed to identify at-risk subpopulations.

Black People↗

A quantitative method for comparing and evaluating manual prosthetic socket modifications.

Manually designed prosthetic sockets are difficult to evaluate since the hand-sculpting modification process does not retain the initial shape for comparison. A quantitative method for defining and comparing manual socket modifications was developed and integrated into the CADVIEW software package. The numerical comparison procedure consisted of a) digitizing premodification and post-modification models of a prosthetic socket, b) aligning these two shapes to a common axis (calculate cross section centroids, determine line of best fit through the centroids, rotate and move the line of best fit to a common axis), and c) displaying the differences in shape both numerically and using a color-coded three dimensional image. Alignment technique testing showed a between-radial-point average error of 2.5 mm using automatic alignment and 1.4 mm after further manual alignment adjustment. The between socket difference values were used to outline individual modifications and save these outlines to disk. Modification outlines from a series of patients were averaged to determine a prosthetist's general modification style. Averaged results from two prosthetists qualitatively supported the effectiveness of this procedure. This alignment and comparison system should help transfer hand-sculpting skills to prosthetic CAD/CAM systems, clinical research, and education for new clinicians.

Amputation Stumps↗

A method for simultaneous recording and assessment of gut contractions and relaxations in vivo.

The normal gut exhibits both contractions and relaxation from a resting tonus. Pathological and pharmacological information may be gleaned from separate measurement of these activities. Methods for recording and analyzing gut contractions have been presented before. We present an extension to the methods, utilising simple foil strain gauges tested here in male Sprague-Dawley rats. Coupled with a computer-based data acquisition and analysis system, we could assess the relaxation and contraction waves recorded simultaneously and from different gut regions in vivo. In contrast with the antrum, where spontaneous motor activity consisted of low frequency relaxations and random contractions, spontaneous duodenal motility was patterned into periodic groups of intense activity interposed by periods of low amplitude, low frequency contractions and relaxations. This grouped activity was propagatory, reminiscent of migrating myoelectrical complexes. When challenged with the ulcerogen cysteamine-HCl (56 mg/100 g s.c.), only duodenal motor activity was affected. Moreover, this treatment had differential effects in the duodenum. Patterned motility was no longer distinguishable, and contraction frequency and amplitude were increased while relaxation amplitude was decreased. This method affords a particularly sensitive and more precise assessment of both contractile and relaxant motor activity in vivo, before and after drug treatment.

Animals↗

Influence of the oxidatively damaged adduct 8-oxodeoxyguanosine on the conformation, energetics, and thermodynamic stability 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 and calorimetric study on a family of DNA duplexes both with and without the oxidative lesion 2'-deoxy-7-hydro-8-oxoguanosine (8-oxodG). Specifically, we have studied a family of eight 13-mer duplexes of the form [5'-GCGTAC[G* or G]CATGCG-3'].[3'-CGCATG[C, A, T, or G]GTACGC-5'] in which G* is the 8-oxodG lesion. These eight duplexes, which we designate by the identity of the variable central base pair (e.g., G*C), reflect two subsets: four duplexes in which the modified guanine base is positioned opposite each of the four possible canonical residues (G*C, G*A, G*G, G*T) and the corresponding four "control" duplexes in which the guanine is not modified (GC, GA, GG, GT). The data derived from our spectroscopic and calorimetric measurements on these eight duplexes allow us to evaluate the influence of the 8-oxodG lesion, as well as the base opposite the lesion, on the conformation, the thermal and thermodynamic stability, and the melting thermodynamics of the host DNA duplex. We find that modification of dG to 8-oxodG (G*) does not change the global DNA duplex conformation as judged by circular dichroism spectra. Despite this structural similarity, our data reveal that the dG to dG* modification does influence duplex thermal and thermodynamic properties, some of which depend on the base opposite the lesion. Thus, apparent structural identity does not mean that two duplexes necessarily will exhibit equivalent thermal and/or thermodynamic properties. In general, we find that the thermodynamic effects induced by the lesion (e.g., GC vs G*C) or by mismatched base pairs (e.g., GC vs GG) can result in relatively large changes in enthalpy which are partially or wholly compensated entropically to produce relatively modest changes in free energy. Our data also suggest that the biologically observed differential recognition of 8-oxodG duplexes and the preferential nucleotide insertion opposite 8-oxodG residues cannot be rationalized simply in terms of large thermodynamic differences.

8-Hydroxy-2'-Deoxyguanosine↗

Azido-iodo-phenyl-analogs of 2',5'-dideoxy-adenosine as photoaffinity ligands for adenylyl cyclase.

Azidoiodophenyl-analogs of 2',5'-dideoxyadenosine were synthesized and tested as potential 'P'-site selective affinity probes for adenylyl cyclases. The 3'-substituted analogs included: 1: 3'-[(4-nitrophenyl)-acetyl]-2',5'-dideoxy-adenosine 2: 3'-[(4-nitrophenyl)-butyryl]-2',5'-dideoxyadenosine 3: 3'-[(4-azido-3-iodophenyl)-acetyl]-2',5'-dideoxyadenosine and 4: 3'-[(4-azido-3-iodophenyl)-butyryl]-2',5'-dideoxyadenosine. The azidoiodo-phenyl-analogs inactivated adenylyl cyclase irreversibly and in a light-dependent manner. This was observed with detergent-dispersed enzyme from rat brain, purified native enzyme from bovine brain, and recombinant Type I bovine adenylyl cyclase expressed in membranes from fall army worm ovarian (Sf9) cells. Inactivation of the recombinant enzyme was inversely dependent on ATP concentration and was not completely prevented by 2',5'-dideoxyadenosine. Inhibition kinetics with the recombinant enzyme in the absence of light suggested two sites of inhibition, whereas with the native Type I enzyme inhibition kinetics exhibited a straightforward noncompetitive mechanism. Occupation of either or both sites by ligand protected the enzyme against denaturation by UV-irradiation per se. The data are consistent with inactivation of the recombinant enzyme occurring both through the 'P'-site and the catalytic active site, but suggest that this is a characteristic of the recombinant enzyme and is not dependent on the probes per se. The data suggest the potential for independent interactions of such ligands with different sites on a given enzyme and also with other enzymes containing adenosine or adenine nucleotide binding domains.

Adenosine Triphosphate↗

Topographic organization of a forebrain pathway involved with vocal learning in zebra finches.

A serial pathway from a thalamic nucleus (DLM; the medial portion of the dorsolateral nucleus of the anterior thalamus) to a cortical region (lMAN; the lateral magnocellular nucleus of the anterior neostriatum) to a motor-cortical region (RA; the robust nucleus of the archistriatum) is necessary for vocal production during song learning in juvenile zebra finches but not for the recitation of a song already learned by adults. To obtain new information about the possible function of the DLM-->lMAN-->RA pathway in vocal learning, we used anterograde and retrograde tract-tracing techniques (pressure injections of DiI and DiA) to map the pattern of axonal connections between these brain regions in adult male zebra finches. Results revealed two topographically organized pathways that traverse the songbird forebrain in parallel. An oval-shaped dorsal/lateral portion of DLM projects solely to the central core of lMAN (lMANcore), whereas a crescent-shaped region, including ventral and medial DLM, projects exclusively to a parvicellular shell that encircles lMANcore (lMANshell). In turn, lMANshell neurons project solely to an arc-shaped region of dorsal archistriatum just lateral to RA (Ad; archistriatum, pars dorsalis), whereas lMANcore neurons project exclusively to RA. We also identified crossed and reciprocal pathways between lMANcore/shell and the lateral portion of the ventral archistriatum, which may contribute to interhemispheric coordination of vocal behavior. A robust topographic organization was observed in the axonal projections from dorsal/lateral-DLM-->lMANcore-->RA and from ventral/medial-DLM-->lMANshell-->Ad, raising the question of what is being mapped within these two forebrain pathways. Because RA projection neurons are organized myotopically with respect to the major vocal (syringeal) muscles (D.S. Vicario, 1991, J. Comp. Neurol. 309:486-494), one possibility is that a mapping of vocal/expiratory musculature is preserved "upstream" within these pathways. Similarly, the presence of song-selective auditory neurons in DLM, lMAN, and RA (A.J. Doupe and M. Konishi, 1991, Soc. Neurosci. Abstr. 18:527) suggests that these pathways might subserve some form of auditory or auditory-motor mapping.

Aging↗