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Biomedical subjects

J Gall

Publications and source records attributed to J Gall.

At least 19 recordsLinked to original sources

Adenovirus type 5 and 7 capsid chimera: fiber replacement alters receptor tropism without affecting primary immune neutralization epitopes.

The efficient uptake of adenovirus into a target cell is a function of adenovirus capsid proteins and their interaction with the host cell. The capsid protein fiber mediates high-affinity attachment of adenovirus to the target cell. Although the cellular receptor(s) for adenovirus is unknown, evidence indicates that a single receptor does not function as the attachment site for each of the 49 different serotypes of adenovirus. Sequence variation of the fiber ligand, particularly in the C- terminal knob domain, is associated with serotype-specific binding specificity. Additionally, this domain of fiber functions as a major serotype determinant. Fiber involvement in cell targeting and its function as a target of the host immune response make the fiber gene an attractive target for manipulation, both from the perspective of adenovirus biology and from the perspective of using adenovirus vectors for gene transfer experiments. We have constructed a defective chimeric adenovirus type 5 (Ad5) reporter virus by replacing the Ad5 fiber gene with the fiber gene from Ad7A. Using the chloramphenicol acetyltransferase reporter gene, we have characterized this virus with respect to infectivity both in vitro and in vivo. We have also characterized the role of antifiber antibody in the host neutralizing immune response to adenovirus infection. Our studies demonstrate that exchange of fiber is a strategy that will be useful in characterizing receptor tropism for different serotypes of adenovirus. Additionally, the neutralizing immune response to Ad5 and Ad7 does not differentiate between two viruses that differ only in their fiber proteins. Therefore, following a primary adenovirus inoculation, antibodies generated against fiber do not constitute a significant fraction of the neutralizing antibody population.

Adenoviridae↗

[Spheres from the oocyte nuclei of the house cricket and the damselfly contain pre-mRNA splicing and pre-rRNA processing factors].

By the method of immunocytochemistry it has been shown that spheres from cricket and damselfly oocyte nuclei contain small nuclear RNA (snRNA) and fibrillarin, a protein involved in pre-rRNA processing. Besides, in cricket oocyte spheres coilin has been revealed, a protein which is part of intranuclear structures in somatic cells called coiled bodies. By the method of nucleic acid hybridization in situ, U1, U2 and U6 snRNAs were identified in spheres of cricket oocytes. Concentration of U2 snRNA was much higher compared to U1 and U6 snRNA. After a longtime (24h) incubation of cricket's ovary in the medium containing 3H-uridin, spheres remained unlabelled by contrast with a heavily labelled karyoplasm. Thus, the data obtained show a homology between spheres from the studied insects and coiled bodies of somatic cells, spheres from amphibian oocytes, and prenucleolar bodies in nuclei formed in vitro in Xenopus laevis egg extracts after adding DNA.

Animals↗

Circumventing the immune response to adenovirus-mediated gene therapy.

Adenovirus-mediated gene transfer experiments have demonstrated an exceptional efficiency of virus uptake and gene expression in a variety of in vivo models. Unfortunately, the efficiency of gene delivery is not accompanied by long-term gene expression. Maximal gene expression peaks during the first week of infection followed by a rapid decline to near baseline levels within several weeks. Data from several laboratories implicate host cellular and humoral immune responses as being responsible for the limited duration of expression and for the inability to successfully readminister a gene using adenovirus vectors. In this study we have examined two strategies which, independently or in combination, circumvent aspects of the host immune response against adenovirus-mediated gene therapy. The first strategy explores induction of immune tolerance in the experimental host as a method to increase the duration of gene expression and as a method to allow readministration of adenovirus expression vectors. Our second strategy is directed at the need to readminister adenoviral vectors to immune competent adult animals. We have demonstrated that a sequential exposure of rats to at least two other adenovirus serotypes does not compromise our ability to successfully administer an Ad5-based CAT expression vector. The characterization of serotype-specific neutralizing response indicates that the construction and use of Ad expression vectors from different serotypes will facilitate a useful adenovirus-based strategy allowing multiple administrations of a target gene.

Adenoviruses, Human↗

Recurrent erythema multiforme: a possible role of foodstuffs.

Seven patients are described, who presented with a history of recurrent episodes of erythema multiforme and who were subsequently found to be sensitive, by patch testing, to benzoic acid. Advice on avoidance of benzoic acid resulted in resolution of attacks in four patients, but three patients who were not able to adhere to an exclusion diet continued to have symptoms. These findings implicate benzoic acid, a food preservative, as an aetiological factor in erythema multiforme. It is proposed that patch testing to food substances should be carried out on patients who present with recurrent erythema multiforme, since avoidance of potential allergens may lead to resolution of symptoms.

Adolescent↗

Relationship between neurosis and personality disorder.

316 psychiatric patients--predominantly out-patients--with a clinical diagnosis of neurosis (International Classification of Disease), were given an interview schedule for assessing personality disorders. Nearly two fifths were rated as having personality disorder, the anankastic type being the most common and sociopathic personality disorder the least. Patients with anxiety, phobic and obsessional neurosis were all significantly more likely to show personality disorder than those with depressive neurosis. Broadly, passive-dependent personalities were linked to anxiety neurosis, anankastic personality disorder to obsessional neurosis, and both anankastic and passive-dependent personalities to phobic neurosis. In a clinical trial of the efficacy of two dosage regimes of phenelzine in 60 patients the presence of personality disorder significantly impaired clinical outcome. The results suggest strongly that the assessment of personality in neurotic disorders is necessary to make an adequate diagnosis and predict the outcome of treatment.

Clinical Trials as Topic↗

Tandemly repeated C-C-C-C-A-A hexanucleotide of Tetrahymena rDNA is present elsewhere in the genome and may be related to the alteration of the somatic genome.

The ribosomal RNA genes of the Tetrahymena macronucleus exist as extrachromosomal, linear molecules. The termini of these molecules have been shown to contain the tandemly repeated hexanucleotide (C-C-C-C-A-A)n. In this study the same or related sequences were found in other locations of the genome. Using the depurination method, we showed that macronuclear DNA contained this sequence even after rDNA had been removed. The sequence was found mainly in the repetitive fraction of the DNA. The presence of this sequence in both the macronucleus and the micronucleus was also shown by Southern hybridization using C-C-C-C-A-A repeat as a probe. Comparison between the hybridization patterns of macronuclei and micronuclei reveals interesting differences. Whereas the two nuclei share the same genetic origin, the majority of the restriction enzyme digestion sites flanking the C-C-C-C-A-A repeat appear to be different. Such a difference was found to be specific for this sequence, because it was not detected when other sequences were used for hybridization. These results suggest that some kind of alteration has occurred in the genome during the formation of the macronucleus, and that the C-C-C-C-A-A repeat may be related to this process.

Animals↗