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Biomedical subjects

A Bakker

Publications and source records attributed to A Bakker.

157 records · Page 9Linked to original sources

Identification of a new lymphocyte subset surface antigen, the expression of which disappears after in vitro and in vivo stimulation. Distribution, biochemistry, and functional studies.

Two monoclonal antibodies (MoAbs) are described (MD 2.6, IgG1 and MD 4.3, IgG2a) that react with a nonlineage specific lymphocyte subset surface antigen. This antigen is expressed on B cells, a subset of both T8+ and T4+ cells, cells that exert killer and natural killer cell activity in vitro, B cells in lymph nodes, and a small percentage of thymocytes. Expression of the antigen was found to be variable on T cells but not on B cells among individuals. Following polyclonal activation, expression of the determinant detected was lost from the cell surface. Both MD+ and MD+ cells responded to PHA and in MLC. MLC resulted in the generation of cytotoxic T lymphocytes and primed T lymphocytes in both the MD+ and MD+ subpopulations. In contrast, the response to soluble antigens was found to reside almost exclusively in the MD-subset. Immunoprecipitation indicates that the MoAbs react with an antigen that has a molecular weight of 220-240 KD which can be cleaved into subunits of 70-80 kD by beta-mercaptoethanol.

Antibodies, Monoclonal↗

A region of the Herpesvirus saimiri genome required for oncogenicity.

Herpesvirus saimiri naturally infects squirrel monkeys (Saimiri sciureus) without producing signs of disease; infection of other New World primates, however, results in a rapidly progressing, malignant, T-cell lymphoma. Results described in this report identify a region of the viral genome that is required for oncogenicity in owl monkeys (Aotus trivirgatus); this region is not required for replication of the virus. This is believed to be the first such genomic region identified in a herpesvirus system.

Animals↗

Synthesis of bovine growth hormone in primates by using a herpesvirus vector.

A strain of herpesvirus saimiri containing a bovine growth hormone (bGH) gene under the control of the simian virus 40 (SV40) late-region promoter was constructed. This strain, bGH-Z20, was replication competent and stably harbored the bGH gene upon serial passage. Nonpermissive marmoset T cells persistently infected with bGH-Z20 produced a 0.9-kilobase RNA which contained all of the bGH exon sequences and appeared to initiate within the SV40 promoter region. However, in permissively infected owl monkey kidney cells, RNAs containing growth hormone sequences appeared to initiate from herpesvirus saimiri promoters positioned upstream from the SV40-growth hormone gene. Persistently infected T cells in culture secreted 500 ng of bGH protein per 10(6) cells per 24 h during the several months of testing. The secreted protein was 21 kilodaltons, the size of authentic bGH. New World primates experimentally infected with bGH-Z20 produced circulating bGH and developed immunoglobulin G antibodies directed against bGH. Because herpesviruses characteristically remain latent in the infected host, these observations suggest a means for replacing gene products missing or defective in hereditary genetic disorders.

Animals↗

Construction of replication-competent Herpesvirus saimiri deletion mutants.

DNA fragments derived from the left end of Herpesvirus saimiri 11 L-DNA were cloned in Escherichia coli by using vector pBR322. Deletions were introduced within a cloned 7.4-kilobase-pair sequence by using restriction endonucleases that cut once or twice within this sequence. Permissive owl monkey kidney-cultured cells were transfected with parental strain 11 viral DNA plus cloned DNA with specific sequences deleted. By screening the progeny of these transfections with a limiting-dilution spot hybridization assay, we isolated recombinant viruses containing deletions in this region. A contiguous 4.5-kilobase-pair sequence representing 4.1% of the coding capacity of the virus was found to be unnecessary for virus replication in cultured cells. These deletion mutants will allow us to test whether sequences in this region are required for the lymphoma-inducing capacity of H. saimiri. These same procedures should also allow us to introduce foreign DNA sequences into this region for studying their expression.

Animals↗

Mapping of RNA transcribed from a region of the Herpesvirus saimiri genome required for oncogenicity.

A region of the Herpesvirus saimiri genome that is not essential for replication of the virus has recently been shown to be required for its oncogenicity in New World primates. We have examined the RNAs derived from this region of the genome in permissively infected cells. Two polyadenylated RNAs, of 4.9 and 2.3 kilobases, were the major species coded for by this region of the genome. These two RNAs, as well as a much less abundant RNA of 6.5 kilobases, were specifically altered in two different nononcogenic deletion mutants of H. saimiri. The 4.9- and 2.3-kilobase RNAs were mapped by S1 nuclease and exonuclease VII digestion of DNA-RNA hybrids. The transcripts were found to be spliced, overlapping, and transcribed from right to left on the genetic map, with their 3' termini each ca. 150 base pairs from the left border between the unique and repetitive DNA regions. These RNAs were not detected at immediate early times after infection. The possible role of these RNAs in the origin of the malignant T-cell lymphoma caused by this virus is discussed.

Animals↗

Evaluation of the use of the Hemalog D in acute lymphoblastic leukaemia and disseminated non-Hodgkin's lymphoma in children.

In 79 children with acute lymphoblastic leukaemia and in 18 children with disseminated non-Hodgkin's lymphoma we investigated whether the automated cytochemical differential leucocyte count (Hemalog D) gives more accurate information than the manual differential count. We concluded that the manual count is superior to the Hemalog-D count with regard to the recognition of blast cells. Furthermore, Hemalog D is not helpful for the differentiation between acute lymphoblastic leukaemia and disseminated non-Hodgkin's lymphoma.

Autoanalysis↗

T-DNA organization in homogeneous and heterogeneous octopine-type crown gall tissues of Nicotiana tabacum.

Octopine-type tumor tissue was obtained both by infection of plants or isolated protoplasts with Agrobacterium tumefaciens and by somatic hybridization of normal and crown gall tobacco cells. Analysis of T-DNA by Southern blotting of clones and uncloned tissue reveals that, whereas tumors induced on plants are heterogeneous mixtures of cells differing in T-DNA organization, each tissue derived from transformed protoplasts or from somatic hybridization is homogeneous. Detailed analysis of T-DNA organization showed that TL- or "core" T-DNA was always present at one or two copies per diploid genome. However, sometimes it was present in a modified form, either deleted, extended, tandemly duplicated or probably methylated. TR-DNA was not detected. The observed variation in the organization of T-DNA in octopine crown gall tissue did not appear to be a characteristic of the way the tissue was derived.

Arginine↗

Two sides of the same coin: Wnt signaling in neurodegeneration and neuro-oncology.

Wnts function through the activation of at least three intracellular signal transduction pathways, of which the canonical beta-catenin mediated pathway is the best understood. Aberrant canonical Wnt signaling has been involved in both neurodegeneration and cancer. An impairment of Wnt signals appears to be associated with aspects of neurodegenerative pathologies while overactivation of Wnt signaling is a common theme in several types of human tumors. Therefore, although therapeutic approaches aimed at modulating Wnt signaling in neurodegenerative and hyperproliferative diseases might impinge on the same molecular mechanisms, different pharmacological outcomes are required. Here we review recent developments on the understanding of the role of Wnt signaling in Alzheimer's disease and CNS tumors, and identify possible avenues for therapeutic intervention within a complex and multi-faceted signaling pathway.

Alzheimer Disease↗

Cognitive therapy by allocation versus cognitive therapy by preference in the treatment of panic disorder.

BACKGROUND: Little is known about the influence of preference for a given therapy or preference against a modality of treatment on the outcome of that treatment. Results so far have been conflicting. The primary aim of this study was to investigate possible differences in outcome between panic disorder patients treated with preferred cognitive therapy and patients treated by randomization with the same intervention. METHODS: A 12-week study comparing 35 patients treated by allocation with 31 patients treated by preference. RESULTS: There were no differences at pretest between the two conditions on demographic or outcome measures. Outcome was assessed with measurements rating the panic frequency and severity of agoraphobia, general anxiety and depression. Both conditions improved significantly on nearly all ratings. There were no significant differences demonstrable between the two conditions on any of the outcome measures. CONCLUSION: Preference for a given therapy is not a powerful moderator of effect in the psychological treatment of panic disorder.

Antidepressive Agents, Tricyclic↗

Increased extracellular calcium concentrations in the isolated rat heart: effects on mitochondrial contact site formation.

In our previous study, mitochondrial creatine kinase (Mi-CK) activity is localised cytochemically in heart tissue. The activity was found to be exclusively localised in mitochondrial contact sites and the surface density of Mi-CK was increased upon myocardial stimulation (Biermans et al., 1989). As calcium is involved as an intracellular messenger of stimulation, we compared hearts noradrenaline-stimulated in vivo with isolated hearts perfused with buffers containing different calcium concentrations on the surface density Mi-CK.

Animals↗