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Biomedical subjects

E M Johnson

Publications and source records attributed to E M Johnson.

At least 361 records · Page 20Linked to original sources
PubMed1979

Different nucleosome structures on transcribing and nontranscribing ribosomal gene sequences.

Monomeric DNA lengths from Physarum nuclear chromatin occur in two subunit forms which differ from each other and from higher oligomers of nucleosomes in content of transcribed ribosomal DNA sequences. Labeled DNA restriction fragments from ribosomal RNA coding regions reanneal most rapidly with DNA from a monomeric subunit fraction. A particles, isolated from growing plasmodia and containing 144 base pairs of DNA in an extended conformation. Higher oligomers of nucleosomes are depleted in sequences from transcribing gene regions but are enriched in sequences from the nontranscribed central spacer of the ribosomal DNA palindrome. Nucleosome configuration on two 26S gene intervening sequences resembles that on adjacent coding regions.

Cell Nucleolus↗
PubMed1979

Phosphorlyation of H1 and H5 histones by cyclic AMP-dependent protein kinase reduces DNA binding.

Phosphorylation of H1 histones by cyclic AMP-dependent protein kinase may be an important transcriptional control mechanism. We have used affinity chromatography to examine the effect of phosphorylation by this enzyme on the DNA-binding properties of calf thymus H1 histones and two highly basic H1 homologues from condensed and transcriptionally silent nuclei: duck erythrocyte H5 and Strongylocentrotus purpuratus sperm H1. Without in vitro phosphorylation, all three histones were eluted from native DNA-Sephadex G-25 columns at salt concentrations which closely resembled those required to extract these histones from nuclei or chromatin. When a small portion of radioactively phosphorylated histone was chromatographed with untreated carrier histone, the phosphorylated species was consistently eluted from the DNA column at slightly lower salt concentrations than the main histone peak. Rechromatography experiments showed that in vitro phosphorylation of H1 can shift its elution position to lower salt concentrations.

Amino Acids↗
PubMed1979

The effects of drug which destroy the sympathetic nervous system on the retrograde transport of nerve growth factor.

It has been proposed that the drugs (6-hydroxydopamine, guanethidine, vinblastine) which are known to destroy sympathetic neurons in neonatal animals do so by preventing the accumulation of retrogradely transported nerve growth factor (NGF). It was found, consistent with the proposal, that administration of 6-hydroxydopamine (100 mg/kg s.c.) or vinblastine (0.4 mg/kg s.c.) 16 h prior to the administration of [125I]NGF complete prevented the accumulation of retrogradely transported [125I]NGF in superior cervical ganglia of neonatal rats. Administration of 6-hydroxydopamine or vinblastine to adult rats (where it does not cause sympathetic neuron cell death) did not completely prevent the retrograde transport of NGF, although 6-hydroxydopamine produced an alteration of the time course of accumulation (early times unaffected, later times depressed). The administration of guanethidine to adult rats (50 mg/kg/day) produced a modest decrease in the accumulation of NGF (40-60%). It would appear, however, that this decrease cannot account for the cytotoxic effects of guanethidine since: (1) sub-cytotoxic doses of guanethidine and non-cytotoxic guanidinium blocking agents also produce modest decreases in the retrograde transport in NGF; and (2) the retrograde transport of [125I]NGF is not affected in neonatal animals until after the neurons are clearly damaged. Hence, the data are entirely consistent with the hypothesis that NGF deprivation caused by 6-hydroxydopamine and vinblastine is the mechanism of the cytotoxic effects of these drugs on sympathetic neurons in neonatal animals. Guanethidine destroys sympathetic neurons by some other mechanism.

Animals↗
PubMed1979

Morphological alterations in the developing fetal rat limb due to maternal injection of chlorambucil.

On day 14 of pregnancy, rats were injected i.p. with 9.5 mg/kg of chlorambucil. At term, all the fetuses were stunted and had obvious skeletal malformations. From days 15-20 of gestation there was a steady progression of cell death and histologic derangement in long bone formation. This began on day 15, the day following exposure to chlorambucil, with extensive cell death of chondroblasts in the long bone primordia. By day 16, dead or dying cells were located in the cartilage model and became associated with a higher than normal matrix to cell ratio. In day 17 limbs, many cells of the cartilage model were irregular in size and shape so that the normally precise cellular arrangement was lacking. On day 18, periosteal and enchondrial calcification was delayed and scanty. The fibular hemimelia observed in all drug-treated term fetuses stained with alizarin appeared to result from lack of development of the proximal half of the cartilage model. The observed alterations, particularly bowing of the ulna, in the teratogen-treated fetuses appeared to result primarily from specific cell death and formation of aberrant cell types but abnormal cell products may also play a role.

Animals↗
PubMed1979

Experimental autoimmune model of nerve growth factor deprivation: effects on developing peripheral sympathetic and sensory neurons.

An experimental autoimmune model of nerve growth factor (NGF) deprivation has been used to assess the role of NGF in the development of various cell types in the nervous system. Adult rats immunized with 2.5S mouse NGF in complete Freund's adjuvant produced antibodies that crossreacted with their own NGF and that were transferred in utero to the fetus and in milk to the neonate. Cross-fostering experiments were carried out to separate the effects of exposure to anti-NGF in utero from those due to exposure through the milk. Anti-NGF transferred in utero and in milk resulted in the destruction of peripheral sympathetic neurons assessed by morphological methods (light microscopy) and biochemical methods (tyrosine hydroxylase activity, choline acetyltransferase activity, and protein content). No effects were observed on the adrenal medulla. Offspring of NGF-immunized females exposed to anti-NGF in utero had a decreased protein content in the dorsal root ganglia and were unable to transport (125)I-labeled NGF injected in the forepaw to the dorsal root ganglia. These results suggest that a subpopulation of sensory neurons is dependent on NGF for survival during some period of fetal development. This model offers the potential for determining the degree and time of dependence of various cell types on NGF.

Animals↗
PubMed1979

Unique sequence arrangement of ribosomal genes in the palindromic rDNA molecule of Physarum polycephalum.

R-loop and restriction mapping procedures reveal the organization of coding regions at each end of the giant rDNA palindrome of Physarum polycephalum. A 19S coding region of 2.10 +/- 0.21 kb is located at each end of a very long central spacer (35.64 +/- 2.08 kb). An internal spacer of 1.66 +/- 0.12 kb lies distal to the 19S gene. The 5.8S rRNA coding region is located in this spacer. The 26S gene lies distal to the internal spacer. The 26S gene is unusual among those of eukaryotes in that it consists of 3 coding regions (alpha, beta and gamma) interrupted by 2 intervening sequences. The 26S alpha (most central) coding segment of 2.41 +/- 0.33 kb is separated from the 26S beta segment by an intervening sequence of 0.68 +/- 0.13 kb. The 26S beta segment (0.70 +/- 0.11 kb) is separated from the most distal 26S gamma segment (0.59 +/- 0.14 kb) by an intervening sequence of 1.21 +/- 0.14 kb. The 2 intervening sequences are present in at least 88% of ribsomal genes from active plasmodia, indicating that genes containing these sequences are transcribed. The rDNA termini contain a heterogeneous region which varies in length by +/- 300 base pairs.

Base Sequence↗
PubMed1979

Mouse protective capabilities of Escherichia coli hybrids expressing Salmonella typhi antigens.

An Escherichia coli hybrid, F1061, expressing Salmonella typhi somatic antigens 9 and 12, and a derivative of this hybrid, E. coli hybrid WR3078, expressing the S. typhi Vi antigen in addition to somatic antigens 9 and 12, were compared with S. typhi Ty2 in experiments to test their ability, as live vaccines, to protect Swiss white mice against death from challenge with a mouse-virulent Salmonella typhimurium hybrid expressing the S. typhi antigens 9, 12, Vi, and d. When the live, vaccinating organisms were administered intraperitoneally, 87.5% of the mice immunized with S. typhi Ty2 survived challenge, as compared with 62.5% of those immunized with E. coli hybrid F1061 and 55% of those inoculated with E. coli hybrid WR3078. When live organisms were administered orally at a dose of 10(9), 67.5% of the mice immunized with S. typhi Ty2 survived challenge as compared with 47.5% of those immunized with E. coli hybrid F1061 and 40% of those administered E. coli hybrid WR3078. Thus, the protection conferred by E. coli hybrid F1061 expressing only the S. typhi somatic antigens, although significant in this system, was inferior to that conferred by S. typhi Ty2 and the addition of the S. typhi Vi antigen to this hybrid (creating E. coli hybrid WR3078) did not enhance that protection.

Administration, Oral↗
PubMed1979

Effects of maternal hypervitaminosis A on perinatal rat lung histology.

Retinyl acetate (160,000 USP/day in corn oil) was administered orally to pregnant Long-Evans rats during the last third of gestation. Postnatal evaluation of this treatment was assessed by examination of histologic sections of lung taken from stillborns and from pups that survived several hours. In all sections from treated litters, expansion of lung either did not appear to have occurred, or was not uniform. Control lung sections were uniformly expanded in all cases. It appears that hypervitaminosis A during the fetal period alters normal lung maturation. These data provide additional supporting evidence that the fetal period is susceptible to teratogens.

Administration, Oral↗
PubMed1979

Unique resistance to guanethidine-induced chemical sympathectomy of spontaneously hypertensive rats: a resistance overcome by treatment with antibody to nerve growth factor.

The chronic administration of high doses of guanethidine to rats produces complete destruction of the peripheral sympathetic nervous system. In a study of the effect of guanethidine-induced sympathectomy on the development of hypertension is spontaneous hypertensive rats (SHR, Okomoto strain), only a partial sympathectomy could be produced as assessed by biochemical parameters (tyrosine hydroxylase activity in ganglia and tissue norepinephrine concentrations) and by evaluation of response to stimulation of vasomotor outflow in pithed rat preparations. Other strains of rats (Sprague-Dawley, American Wistar, Kyoto Wistar) were uniformly sensitive to guanethidine sympathectomy. The resistance to guanethidine was not due to a lower accumulation of guanethidine in the neurons of SHR. Addition to the guanethidine treatment of low doses of antibody to nerve growth factor (NGF), which itself produced only a modest sympathectomy, resulted in an almost complete sympathectomy. SHR did not become hypertensive when sympathectomized by combined guanethidine-anti NGF. These results show that the sympathetic neurons of SHR differ from those of other strains with respect to sensitivity to guanethidine cytotoxicity and suggest the possibility of a role for NGF in that altered responsiveness.

Animals↗
PubMed1978

Effect of chronic clonidine treatment and withdrawal on tyrosine hydroxylase activity in peripheral ganglia and the locus coeruleus.

As is observed clinically, cessation of chronic clonidine treatment in the rat results in a syndrome characterized by sympathetic hyperactivity. After three weeks of chronic oral administration of clonidine, tyrosine hydroxylase (TOH) activity was unchanged in superior cervical ganglia and locus coeruleus, but was reduced (45%) in the celiac ganglia. Abrupt cessation of treatment resulted in increases in TOH activity in superior cervical and celiac ganglia (to 135 and 250% of controls) and in the locus coeruleus (170% of control). These data suggest a selective effect of clonidine treatment and withdrawal on vasomotor fibers. A mechanism explaining physical dependence on clonidine is proposed.

Animals↗
PubMed1978

Characterization of the retrograde transport of nerve growth factor (NGF) using high specific activity [125I] NGF.

The process of the retrograde transport of nerve growth factor (NGF) has been recharacterized using a high specific activity preparation of[125I]NGF. Most of the general conclusions reached in the previous studies of Hendry, Thoenen and co-workers have been confirmed. However, significant quantitative differences were noted. Intraocular (anterior eye chamber) administration of[125I]NGF (less than 10 ng) resulted in accumulation in the superior cervical ganglia beginning at about 4 h. The ratio of radioactivity in the ipsilateral contralateral ganglia was 15--30:1. Maximal accumulation was seen at about 12h in the hamster and 16 h in rats. This pattern was quite different from that seen in other tissues. The uptake system from the eye of the rat was saturable (half-maximal at 15 ng) with maximal accumulation of 35--40 pg/ganglion. Systemic administration of[125I]NGF (200 ng) to adult rats resulted in no accumulation in SGG or celiac ganglion prior to 3 h, with subsequent rapid accumulation by 6 h and a rapid fall in radioactivity after 12 h. A similar time course was seen in 5-day-old rats, although the time curve was shifted slightly toward shorter time. The radioactivity in ganglia co-migrated with native NGF by SDS gell electrophoresis. Cytochrome c of comparable specific activity was not transported, and NGF did not stimulate the uptake and transport of cytochrome c. The retrograde transport of[125I]NGF was inhibited by the co-administration of biologically active, but not inactive, oxidized derivatives of NGF. By any route of administration, a significant percentage of the transported[125I]NGF was found in a purified nuclear fraction of the ganglia. Coupled with previous observations of specific nuclear NGF receptors in embryonic chick and sympathetic ganglia, this suggests that, after internalization and retrograde transport, NGF may directly act on the nucleus to produce at least some of its effects on the responsive cell.

Age Factors↗
PubMed1978

The use of netropsin with CsCl gradients for the analysis of DNA and its application to restriction nuclease fragments of ribosomal DNA from Physarum polycephalum.

Netropsin binds to DNA in caesium chloride density gradients and reduces the density of the DNA. The DNA is saturated at a netropsin/DNA weight ratio of about 6 and the change in density, deltarho, at saturation is given by deltarho = -109 (dA + dT content)1.87 mg/ml for the six DNAs tested covering dA + dT contents from 0.28 to 0.69. At lower netropsin/DNA ratios the observed density shifts are consistent with a two-site model for netropsin binding to DNA. Netropsin approximately doubles the resolution of Physarum polycephalum nucleolar satellite DNA from main-band DNA. The fragments of P. polycephalum nucleolar satellite DNA obtained with the restriction endonuclease HindIII do not separate on CsCl gradients, even in the presence of netropsin, which shows that the transcribed and non-transcribed sequences in this DNA have similar nucleotide compositions.

Centrifugation, Density Gradient↗