PubMed Health⌕ Search

Biomedical subjects

J E Shaw

Publications and source records attributed to J E Shaw.

At least 19 recordsLinked to original sources
PubMed1992

Analysis of the Caenorhabditis elegans axonal guidance and outgrowth gene unc-33.

Mutations in the unc-33 gene of the nematode Caenorhabditis elegans lead to severely uncoordinated movement, abnormalities in the guidance and outgrowth of the axons of many neurons, and a superabundance of microtubules in neuronal processes. We have cloned unc-33 by tagging the gene with the transposable element Tc4. Three unc-33 messages, which are transcribed from a genomic region of at least 10 kb, were identified and characterized. The three messages have common 3' ends and identical reading frames. The largest (3.8-kb) message consists of the 22-nucleotide trans-spliced leader SL1 and 10 exons (I-X); the intermediate-size (3.3-kb) message begins with SL1 spliced to the 5' end of exon V and includes exons V-X; and the smallest (2.8-kb) message begins within exon VII and also includes exons VIII-X. A gamma-ray-induced deletion mutation situated within exon VIII reduces the sizes of all three messages by 0.5 kb. The three putative polypeptides encoded by the three messages overlap in C-terminal sequence but differ by the positions at which their N termini begin; none has significant similarity to any other known protein. A Tc4 insertion in exon VII leads to alterations in splicing that result in three approximately wild-type-size messages: the Tc4 sequence and 28 additional nucleotides are spliced out of the two larger messages; the Tc4 sequence is trans-spliced off the smallest message such that SL1 is added 13 nucleotides upstream of the normal 5' end of the smallest message.

Amino Acid Sequence↗
PubMed1979

Determination of submicrogram quantities of clonidine in biological fluids.

A sensitive and specific GLC method using electron-capture detection was developed for clonidine in plasma and urine. Di-perfluoroacyl derivatives of both clonidine and the 4-methyl analog of clonidine (used as an internal standard) were formed, and an extraction process was developed for the removal of excess derivatization reagent and endogenous biological compounds; the assay permitted quantification of 25 pg of clonidine/ml in a 4-ml plasma sample. The assay was used to elucidate the time course of plasma concentrations in a normotensive subject following oral administration of 50, 100, and 200 microgram of clonidine hydrochloride and also to determine unchanged drug excreted in the urine.

Chromatography, Gas↗
PubMed1979

Lambda encodes an outer membrane protein: the lom gene.

lambda infected minicells synthesize a polypeptide (M(r) = 20,500) which is incorporated almost exclusively into the outer membrane of the minicell envelope. The gene (lom = lambda outer membrane) encoding this polypeptide has been mapped in the non-essential region of the lambda genome between coordinates 39.4% and 40.7% of lambda.

Bacterial Outer Membrane Proteins↗
PubMed1979

Nucleosomal structure of Epstein-Barr virus DNA in transformed cell lines.

Micrococcal nuclease digestion was used to analyze Epstein-Barr virus (EBV) DNA structure in nuclei of transformed cells. Digests of virus-producing (P3HR-1), non-virus-producing (Raji), and superinfected Rajii cell nuclei were fractionated by electrophoresis on agarose gels, transferred to nitrocellulose, and hybridized to 32P-labeled EBV DNA. The viral DNA of Raji nuclei produced a series of bands on electrophoresis whose lengths were integral multiples of a unit size, which was the same as the repeat length of host DNA. Viral DNA in nuclei of P3HR-1 and superinfected Raji cells produced faintly visible bands superimposed on a smear of viral DNA which dominated the hybridization pattern. No differences were detected in the patterns when total DNA digests from Raji, P3HR-1, and an EBV DNA-negative cell line (U-698M) were analyzed by ethidium bromide staining or by hybridization with the use of 32P-labeled lymphoblastoid cell DNA as probe. We conclude that the EBV episomal DNA of Raji cells is folded into nucleosomes, whereas most of the viral DNA of P3HR-1 and superinfected Raji cells is not. This pattern of DNA organization differs signficantly from that in papova group viruses.

Burkitt Lymphoma↗
PubMed1979

Effect of transdermally administered scopolamine in preventing motion sickness.

The efficacy of transdermally administered scopolamine was compared with the efficacy of oral dimenhydrinate and placebo therapy in the prevention of motion-induced mausea in a vertical oscillator; medications were administered on a double-blind cross-over basis, with the order of treatments counterbalanced. Thirty-five subjects known to be susceptible to the stimulus were utilized. A placebo effect reduced the motion sickness incidence (MSI) from 100% to 59%. Administration of dimenhydrinate reduced the MSI to 32%, and use of the transdermal therapeutic system scopolamine (TTS-scopolamine) further reduced the MSI TO 16%. TTS-scopolamine afforded 73% protection against motion-induced nausea, compared to 46% protection with dimenhydrinate. The TTS-scopolamine is designed to remain in the body for 72 hours, providing advantages over intramuscular or oral administration of scopolamine, which include reduced daily dosage, and an effective alternate to the gastrointestinal tract for administrating medication at times of gastrointestinal distress.

Administration, Topical↗
PubMed1978

Pharmacokinetics of drug permeation through human skin.

Based on sorption and permeation characteristics of scopolamine in human skin in vitro and drug elimination kinetics obtained from pharmacokinetic studies, a mathematical model was developed for estimating and optimizing the temporal pattern of scopolamine delivery from a transdermal therapeutic system through human skin in vivo. Experimentally measured scopolamine delivery in vivo conformed to this model.

Administration, Oral↗
PubMed1978

Identification of the N gene protein of bacteriophage lambda.

The N gene protein, pN, of bacteriophage lambda stimulates early gene transcription by allowing mRNA chain elongation to proceed into genes distal to transcription termination sites normally recognized by the Escherichia coli transcription termination protein rho. pN has previously eluded detection on sodium dodecyl sulfate/polyacrylamide gels because of its small size, its instability, and the difficulty of distinguishing pN itself both from host proteins and from other early lambda proteins whose synthesis depends on pN action. These problems have now been overcome and we find that the major form of pN present in crude cell extracts of infected cells has an apparent molecular weight of 13,500. lambdabio256, a deletion-substitution mutant terminating in N, codes for a shorter pN of molecular weight 12,500. A nonsense fragment of 10,500 molecular weight coded by lambdaN(am7) has also been identified. These conclusions are based on examination of the electrophoretic profiles of the proteins synthesized after infection of UV-irradiated E. coli by various lambdaN(-) temperature-sensitive, nonsense, and deletion-substitution mutants. It has also been possible to distinguish pN itself from other early lambda polypeptides by infecting ron(-) cells with either lambdaN(mar) phage allowing pN synthesis but not pN action or lambdaN(am) phage defective in pN synthesis and pN action. Our results together with previous data are discussed with respect to the possible existence of multiple molecular weight forms of pN and the location of the coding sequences in the N gene region.

Coliphages↗
PubMed1978

Factors influencing the percutaneous absorption of drugs.

The skin is the most readily accessible organ of the human body; only a fraction of a millimeter separates its surface from the underlying capillary network. Yet, skin protects superbly against damage by micro- and macro-molecular entities, as well as against uncontrolled loss of vital biological substances, by virtue of its astonishingly low permeability to such substances. We have reexamined and attempted to reconcile the barrier characteristics of skin in terms not only of its composition and microstructure, but also of present understanding of membrane permeability and permselectivity. The principal barrier to percutaneous transport is localized within the stratum corneum. We have developed a mathematical model of this tissue as a two-phase protein-lipid heterogeneous membrane, which correlates the permeability of the membrane to a specific penetrant with the water solubility of the penetrant and with its lipid-protein partition coefficient. We have also found that a simplistic model of the sorption process, which invokes the coexistence of dissolved and mobile sorbed molecules in equilibrium with site-bound and immobile molecules within the membrane, accurately correlates experimental sorption data and transient transport measurements. The interstitial lipid phase of the stratum corneum is the cause of the exceedingly low, apparent diffusivity of drugs (e.g. scopolamine) and, in this regard, acts as the principal permeation barrier, whereas the drug sorbed by the stratum corneum is localized predominantly within the protein phase of the tissue. We have also found that the effects of the permeation adjuvant, dimethyl sulfoxide, on skin permeability are entirely consistent with accepted sorption-diffusion models of membrane transport, when changes in penetrant activity with changes in solvent composition and tissue microstructure induced by osmotic shock are properly allowed for.

Dimethyl Sulfoxide↗
PubMed1978

Replication of Epstein-Barr virus DNA in epithelial cells in vivo.

Epstein-Barr virus (EBV)-specific complementary RNA (cRNA) was hybridized in situ to oropharyngeal epithelial cells taken from patients with infectious mononucleosis. Cells from patients shedding virus in the throat hybridized signifnicant quantities of cRNA, whereas cells from EBV-negative sources did not. The degree of hybridization indicated a large EBV genome number per infected epithelial cell and suggested that these cells were the source of virus found in the throat. This finding may explain the presence of the EBV genome in the malignant epithelial cells of nasopharyngeal carcinoma.

Autoradiography↗
PubMed1977

Synthesis of Epstein-Barr virus DNA in vitro: effects of phosphonoacetic acid, N-ethylmaleimide, and ATP.

Nuclei from superinfected Raji cells synthesized Epstein-Barr Virus (EBV) DNA in vitro in the absence of cell DNA synthesis. The synthesis of EBV DNA in vitro was inhibited by phosphonoacetic acid and N-ethylmaleimide, and maximum synthesis was achieved in the absence of an ATP-regenerating system. Nuclei from mock-infected cells required an ATP-regenerating system for maximum DNA synthesis.

Acetates↗
PubMed1975

Transformation of cells by herpes simplex virus--fact or fantasy?

The replication of herpes simplex virus types 1 and 2 is defective in XC cells. One lesion is the failure of viral proteins to be transported to the cell nucleus. The resistance of XC cells to the toxic effects of herpes simplex virus is apparently not due directly to the presence of RNA tumor virus in these cells. Other cell lines transformed by RNA tumor viruses exhibited no comparable resistance. The nature of the association between HSV and cell for a number of generations after first selecting "transformants" is not yet established; on prolonged subculture, much of the original HSV information fails to be expressed. Not more than approximately to 0.1 viral genomes per cell remains permanently associated with the host DNA. The "transformants" retain the capacity to synthesize HSV-specific polypeptides, as determined by radioimmunoprecipitation. The "transformants" have a number of characteristics which distinguish them from parental cells, and such characteristics in the light of the immunological data suggest that XC cells exposed to HSV can permanently retain HSV-specific information.

Antigens, Viral↗