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Biomedical subjects

E J Smith

Publications and source records attributed to E J Smith.

At least 109 records · Page 6Linked to original sources
PubMed1988

Genetic cellular resistance to subgroup E avian leukosis virus in slow-feathering dams reduces congenital transmission of an endogenous retrovirus encoded at locus ev21.

The gene ev21, which encodes an infectious endogenous subgroup E avian leukosis virus (ALV-E), designated EV21, is closely linked to the sex-linked, slow-feathering (SF) gene K. To address the relationship between congenital transmission of EV21 and host susceptibility to ALV-E infection, SF roosters that were heterozygous for the dominant gene for susceptibility to ALV-E were mated with ev-negative rapid-feathering (RF), subgroup E-resistant dams to produce SF and RF progeny. The SF female progeny that were heterozygous ALV-E susceptible were viremic at hatch and, when mature, consistently shed the ALV group-specific antigen, p27, in the egg albumen they produced. In contrast, SF females that were homozygous ALV-E resistant were neither viremic at hatch nor shedders of ALV p27. Infectious ALV-E assays of progeny from susceptible and resistant SF dams confirmed that maternal cellular resistance to ALV-E limited congenital transmission of EV21. It is proposed that, in progeny, immunologic tolerance toward exogenous ALV infection due to congenital transmission of antigenically related endogenous viruses may be abrogated by selection for cellular resistance to ALV-E in SF lines used as female parents of feather-sexed crosses.

Animals↗
PubMed1988

Influence of congenital transmission of endogenous virus-21 on the immune response to avian leukosis virus infection and the incidence of tumors in chickens.

After contact exposure to Strain RPL-40 avian leukosis virus-infected hatchmates, a dilatory neutralizing antibody response and prolonged RPL-40 viremia was found among most pullets that were congenitally infected with endogenous virus 21 (EV21). Conversely, most of the hatchmates that were not congenitally infected seroconverted within 10 wk after exposure to Strain RPL-40 virus. Compared with noncongenitally infected hatchmates, EV-21 infection-induced tolerance to pathogenic avian leukosis viruses was reflected in a significantly higher incidence of lymphomas in congenitally infected hens. The rate of seroconversion and the incidence of RPL-40 virus-induced tumors among noncongenitally infected daughters from slow-feathering dams homozygous resistant to EV were similar to those found among daughters of rapid-feathering dams that lacked genetic locus ev21. Results suggest that selection for resistance to EV may eliminate tolerance toward oncogenic field strains of avian leukosis viruses and may improve the performance of progeny from a feather-sex cross.

Animals↗
PubMed1987

Effect of dopamine antagonism on carotid chemoreceptor interspike intervals.

As a means of examining the role of dopamine in chemotransduction, we examined the spike interval pattern from single carotid body chemoreceptors before and following dopamine antagonism. Before dopamine antagonism, chemoreceptor joint interval variability was less than the variability of the same spike interval series placed in shuffled order. This lower variability was abolished by dopamine antagonism with haloperidol. These data suggest that dopamine release reduces chemoreceptor interspike variability in vivo and that endogenous, local dopamine release is related to the activity level of a single chemoreceptor afferent.

Action Potentials↗
PubMed1987

Transgenic chickens: insertion of retroviral genes into the chicken germ line.

We infected early chicken embryos by injection of wild-type and recombinant avian leukosis viruses into the yolk of unincubated, fertile eggs. The viremic males (designated generation 0 (G-0] were tested for transmission of proviral DNA to their G-1 progeny. Nine of 37 G-0 viremic males were mosiac and proviral DNA was transmitted to their progeny at frequencies varying from 1 to 11%. All of the G-1 progeny examined by restriction enzyme analysis for clonality of proviral junction fragments had one to three simple but different fragments. The proviral DNA was transmitted from G-1 to the G-2 progeny in a Mendelian fashion thus proving that retroviral genes have been inserted into the chicken germ line. One of the viruses is a candidate vector for insertion of foreign genes into the chicken germ line.

Animals↗
PubMed1987

The organization of mesodermal pattern in Xenopus laevis: experiments using a Xenopus mesoderm-inducing factor.

In this paper, we study the mechanism by which a Xenopus cell line-derived mesoderm-inducing factor (MIF) might establish the spatial pattern of cellular differentiation in the mesoderm. The effects of the factor on competent animal pole tissue are consistent with it being identical to the natural mesoderm-inducing factor. The signal can only act on those membrane domains of the animal pole that face the blastocoel, but it can be stably recorded there, such that axial mesoderm is formed, after 15 min exposure or less. This exposure can end some hours, or several cell cycles, before the onset of RNA synthesis yet nevertheless be fully effective, although competence to respond also extends well after the onset of transcription. Exposure of the entire blastocoel lining of intact embryos to MIF causes a synchronous and sudden transformation of the behaviour and adhesive properties of all inner animal cap cells. This transformation mimics and is contemporaneous with the involution behaviour of normal mesoderm in the early gastrula marginal zone. Although high concentrations of MIF totally disorganize gastrulation, lower concentrations permit gastrulation to proceed. However, the pattern of mesoderm in these embryos is disrupted and ectopic mesoderm is formed around the blastocoel remnant. When MIF is injected directly into blastomeres, rather than into the blastocoel, it has no effect. This suggests that the molecule is secreted from source cells and affects target cells through an extracellular receptor. Finally, we show that small pieces of animal pole tissue recently exposed to MIF go on to produce morphogenetic signals perhaps distinct from MIF. We discuss the role of these signals in establishing and modifying the spatial pattern of cellular differentiation in the mesoderm of Xenopus.

Animals↗
PubMed1987

Systemic salmonellosis in patients with disseminated histoplasmosis. Case for 'macrophage blockade' caused by Histoplasma capsulatum.

Five patients are described with disseminated histoplasmosis and systemic salmonellosis. Four of these patients were also immunocompromised because of the acquired immunodeficiency syndrome in two patients and renal transplantation in another two patients. Histologic studies in two patients showed histiocytes that were heavily laden with Histoplasma capsulatum yeast-phase organisms. We postulate that diffuse parasitization of the reticuloendothelial system (RES) by Histoplasma organisms may cause "RES blockade," which then predisposes to systemic salmonellosis, as reported in certain other infections and in sickle cell anemia.

Adult↗
PubMed1986

Selective shedding and congenital transmission of endogenous avian leukosis viruses.

Shedding and congenital transmission of endogenous avian leukosis viruses were studied in viremic White Leghorn hens exogenously infected with viruses with endogenous long terminal repeats (LTRs) and in four semicongenic lines of hens that naturally express infectious endogenous viruses (EVs). Relatively high titers of infectious virus EV7 (encoded at locus ev7), Rous-associated virus-0 (RAV-0), and recombinant 882/-16 RAV-0 were detected in blood cells and sera from exogenously infected hens, but marked differences were noted in the incidence of congenitally infected progeny. In enzyme immunoassays that detect viral group-specific antigen, little or no p27 was detected in albumens from dams infected with RAV-0. However, hatchmates infected with either EV7 or recombinant 882/-16 RAV-0, which was constructed with an RAV-0 LTR, shed high titers of p27. Similarly, semicongenic hens that expressed RAV-0 (EV2) (encoded at locus ev2) shed little or no p27 into albumens, but hens that harbored ev10, ev11, and ev12 shed high titers of p27. A slower electrophoretic mobility of p27, considered to be characteristic of EVs that are restricted in congenital transmission, was not associated with low levels of shedding or congenital transmission; p27 from other EVs and p27 from an avian leukosis virus field strain, all of which are shed at high levels, had mobilities identical to that of p27 from RAV-0. Although shedding and congenital transmission appear to be controlled by the viral genome, there was no correlation between low efficiency of shedding or congenital transmission and endogenous LTR or p27 sequences.

Animals↗
PubMed1986

The dendritic origins of penicillin-induced epileptogenesis in CA3 hippocampal pyramidal cells.

Experiments were performed in order to identify the sites of epileptiform burst generation in rat hippocampal CA3 pyramidal cells. A subsequent slow field potential was studied, which is associated with afterdischarge generation. Laminar field potential and current source-density (CSD) methods were employed in hippocampal slices exposed to penicillin. Simultaneous intracellular and extracellular field recordings from the CA3 pyramidal cell body layer showed that whenever an epileptiform burst was recorded extracellularly, individual CA3 neurons underwent an intense depolarization shift. In extracellular records a slow negative field potential invariably followed epileptiform burst generation. In approximately 10% of slices, synchronous afterdischarges rode on the envelope of this negative field potential. Intracellularly a depolarizing afterpotential followed the depolarization shift and was coincident with the extracellular slow negative field potential. A one-dimensional CSD analysis performed perpendicular to the CA3 cell body layer showed that during epileptiform burst generation large current sinks occur simultaneously in the central portions of both the apical and basilar dendrites. The average distance of the peak amplitude for these sinks from the center of the cell body layer was 175 +/- 46.8 microns and 158 +/- 25.0 microns, respectively. A large current source was recorded in the cell body layer. Smaller current sources were observed in the distal portions of the dendritic layers. During the postburst slow field potential a current sink was recorded at the edge of the cell body layer in stratum oriens--a region referred to as the infrapyramidal zone. Simultaneous with the current sink recorded there, smaller sinks were often observed in the dendritic layers that appeared to be "tails" or prolongations of the currents underlying burst generation. Two-dimensional analyses of these field potentials were performed on planes parallel and perpendicular to the exposed surface of the slice. Isopotential contours showed that the direction of extracellular current is mainly orthogonal to the CA3 laminae. Correction of CSD estimates made perpendicular to the cell body layer for current flowing in the other direction did not alter the location of computed current sources and sinks. In order to show that the dendritic currents associated with epileptiform burst generation were active sinks, tetrodotoxin (TTX) was applied locally to the dendrites where the current sinks were recorded.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

Gene insertion into the chicken germ line by retroviruses.

We injected chick syncytial strain of reticuloendotheliosis virus (CS-REV) and wild type and recombinant avian leukosis virus (ALV) near the blastoderm of unincubated fertilized embryos and CS-REV intra-abdominally at day of hatch, and we progeny tested the surviving ALV viremic males and REV viremic males and females for transmitted viral genetic material. A number of positive progeny were identified and their deoxyribonucleic acid (DNA) analyzed for restriction enzyme fragments that hybridized with viral genetic material. Most of the progeny had simple restriction enzyme patterns unlike the viremic parents or congenitally infected progeny. This is suggestive evidence that retroviral genetic information has been inserted into the germ line of chickens.

Animals↗
PubMed1985

Time course of glomerular endothelial injury related to pulsatile perfusion preservation.

To elucidate the time course of glomerular and arterial endothelial injury resulting from pulsatile perfusion preservation of human kidneys, we examined two kidneys, one at 16 and the other at 42 hr, for which no suitable recipient could be found. The scanning electron microscope revealed subtle changes at 16 hr in the filtration barrier. These included mild endothelial swelling with an increase in the appearance of bulbous processes, and elongated fenestrae. The visceral epithelial surface was normal as was the arterial endothelial surface. By 42 hr the glomerular endothelial surface displayed very prominent cytoplasmic ridges and clearly distorted fenestrae. The arterial endothelium exhibited a tendency to separate from the vessel wall. The proximal tubular epithelium revealed scattered loss of microvilli. These changes are similar in kind to, albeit less severe than, those described after 60 hr of perfusion. They may represent cell swelling following ischemia, or be the result of altered cell permeability engendered by low temperature. The possibility remains that such changes could be minimized by modifying the perfusate. Scanning electron microscopy provides a versatile tool in the study of vascular and other surfaces of tissues stored with perfusion preservation.

Endothelium↗
PubMed1985

Haloperidol-induced suppression of carotid chemoreception in vitro.

Effects of antagonism of endogenous dopamine with haloperidol on single-unit frequency, interspike interval distribution, and interval serial dependency of the cat sinus nerve were tested using an in vitro carotid body-sinus nerve superfusion technique. A dose dependency of inhibition by haloperidol (0.05-2.0 microgram/ml) was observed. Superfusion with 1-2 microgram/ml haloperidol significantly reduced frequency within 5 min (P less than 0.05) and caused a complete cessation of firing within 25 min in 5 of 10 chemoreceptor units. Frequency recovered to control during drug washout. Acetylcholine (10-micrograms/ml superfusion or 500-micrograms bolus) increased sinus nerve activity under control conditions but not during superfusion with haloperidol. No effect of haloperidol on impulse serial dependency was detected. However, interval distribution was significantly altered by haloperidol in five of six chemoreceptor units. Our results suggest an excitatory role for dopamine in carotid chemoreception.

Action Potentials↗
PubMed1985

Interspike interval dependency from arterial chemoreceptors.

The carotid body impulse generator has been previously characterized as a Poisson-type random process. We examined the validity of this characterization by analyzing sinus nerve spike trains for interspike interval dependency. Fifteen single chemoreceptive afferents were recorded in vivo under hypoxic-hypercapnic conditions, and approximately 1,000 consecutive interspike intervals for each fiber were timed and analyzed for serial dependence. The same set of intervals placed in shuffled order served as a control series without serial dependence. The original spike interval trains showed significantly negative first-order serial correlation coefficients and less variability in joint interval distributions than did the shuffled interval trains. These results suggest that the chemoreceptor afferent train is not random and may reflect a negative feedback system operating within the carotid body that limits variation about a mean frequency.

Action Potentials↗
PubMed1984

beta-Adrenoceptor blockade spares chemoreceptor responsiveness to hypoxia.

The effect of beta-adrenoceptor blockade on the carotid body chemoreceptor response to hypoxia was assessed in anesthetized and paralyzed cats. Propranolol, atenolol and ICI 118,551 each abolished the enhancement of chemoreceptor activity produced by i.v. infusion of exogenous isoproterenol; however, the blocking drugs did not significantly diminish the increase in chemoreceptor neural discharge induced by hypoxia. These results do not support the hypothesis that beta-adrenergic receptors play an essential role in the chemoreceptor response to oxygen deprivation.

Animals↗
PubMed1984

Characterization of a solitary long terminal repeat of avian endogenous virus origin.

A recombinant lambda phage library constructed with a partial EcoR1 digest of DNA from a normal RPRL line 15B chicken was screened using 32P-labeled plasmid containing Rous-associated virus (pRAV-2). Nucleotide sequence analyses of a fragment of one subclone revealed the presence of a solitary long terminal repeat (LTR) that is similar to the LTRs of avian endogenous retroviruses ev1 and ev2. This LTR is flanked by unique 6 bp direct repeats characteristic of the target site for duplication of avian leukosis viruses.

Animals↗
PubMed1984

Non-random chemoreceptor activity during superfusion in vitro.

As a means of probing the chemotransducer, impulse sequences from in vitro, superfused sinus nerve-carotid body preparations were analyzed for departures from randomness. Twelve of 17 spike trains showed interval histograms that did not differ significantly from exponential. Thus these sequences resembled a Poisson (random) process with respect to time-independence of probability of occurrence of an event. However, 5 spike trains departed significantly from the exponential distribution forcing rejection of the Poisson model in these cases. Furthermore, mean interval vs standard deviation analysis revealed a significant positive correlation among intervals. These data suggest that the carotid body impulse generator possesses an intrinsic regularity and that the Poisson model does not accurately describe the in vitro sinus nerve interspike interval sequence.

Action Potentials↗