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Biomedical subjects

G Butler

Publications and source records attributed to G Butler.

30 records · Page 2Linked to original sources

Identification, purification, and characterization of a mast cell-associated cytolytic factor related to tumor necrosis factor.

The role of mast cells and mast-cell-derived factors in natural cytotoxic reactions was investigated. Cultured and freshly isolated murine mast cells are shown to be cytotoxic to WEHI-164 and YAC-1 targets in 18-hr viability assays but not in 4-hr assays. Here, we describe a cytotoxic factor in murine mast cells that is immunologically related to tumor necrosis factor (TNF). This TNF-like factor lyses WEHI-164 cells with a slow time course requiring 16-20 hr for the lytic reaction to complete. Antibodies specific for human and murine TNF and human lymphotoxin partially block mast cell lysis of WEHI-164 cells. These antibodies react on immunoblots with one major mast cell protein band of 50 kDa. Immunoblot analysis shows this factor in cloned and uncloned cultured mouse mast cells and in mature "connective tissue-type" mast cells freshly purified from rat or mouse peritoneal cavities. The amount of this factor is greatly enhanced in cells that have been stimulated with a combination of phorbol ester/concanavalin A or bacterial lipopolysaccharide. Subcellular fractionation analysis of mast cells with Percoll gradients reveals two pools of TNF-related cytotoxic activity that are associated with free cytosolic material and granule fractions. In contrast to cytotoxic T lymphocytes and natural killer cells, granule-enriched fractions of mast cells do not contain any hemolytic activity. The localization of the TNF-like molecule in mast cell granules may play a strategical role in the rapid delivery of this mediator to the target cell membrane following cell surface stimulation and degranulation.

Animals

GAL1-GAL10 divergent promoter region of Saccharomyces cerevisiae contains negative control elements in addition to functionally separate and possibly overlapping upstream activating sequences.

The upstream activating sequence (UASG) of the adjacent and divergently transcribed GAL1 and GAL10 promoters of Saccharomyces cerevisiae regulates the induction of the corresponding genes in response to the presence of galactose. We constructed chimeric yeast promoters in which a different UAS, UASC from the iso-1-cytochrome c (CYC1) gene of S. cerevisiae, was fused at different locations upstream of GAL1 (UASC-GAL1 promoters) or GAL10 (UASC-GAL10 promoters) and used to monitor the activity of UASG in cells grown in the presence or absence of galactose. Though the CYC1 promoter is fully induced in yeast grown in glycerol medium, UASC-GAL chimeric promoters containing UASG were repressed as much as 400-fold (UASC-GAL1) or 1350-fold (UASC-GAL10) in this growth medium. Several distinct portions of the GAL1-GAL10 divergent promoter region blocked the UASC-induced expression of the GAL1 and GAL10 promoters, whereas others did not, suggesting that several distinct negative control elements are present that may repress transcription of GAL1 and GAL10 in the absence of galactose. The approximate locations of these negative control elements were delimited to sites adjacent to or possibly overlapping the sites at which the positive control protein GAL4 binds in UASG. Deletion derivatives of GAL4 that fail to induce transcription from the wild-type GAL promoters but retain the DNA binding domain significantly derepressed the expression of the UASC-GAL chimeric promoters. These results, combined with those of earlier studies, suggest the possibility that GAL4 normally induces transcription of GAL1 and GAL10 by blocking the activity of these negative control elements, in addition to stimulating transcription by a mechanism of positive control.

Chromosome Mapping

Anxiety management for persistent generalised anxiety.

A preliminary controlled investigation of the effectiveness of Anxiety Management as a treatment for generalised anxiety disorder (GAD) is described. Patients with a primary diagnosis of GAD, in which the current episode had lasted for at least 6 months but not more than 2 years, were included. Anxiety Management, a self-help treatment including procedures for managing somatic and cognitive symptoms, and for dealing with avoidance and low self-confidence, was given either immediately or after a 12-week waiting period. The average length of treatment was 8.7 sessions. Highly significant changes in anxiety, depression, and problem ratings were shown after treatment. These changes were replicated when the waiting list group had also received treatment, and gains were maintained by both groups for 6 months. Similar degrees of improvement and maintenance of change were shown in subgroups with and without minor depressive disorder or recurrent panic attacks.

Adult

A novel approach for obtaining and identifying monoclonal antibodies that react with differentiation-specific antigens using human hybrid cells.

HeLa X keratinocyte hybrid cells have been used as immunogens to generate monoclonal antibodies against differentiation-specific antigens. A key feature of the experimental system is that the hybrid cells are undifferentiated in culture and yet terminally differentiate in the mouse. The properties of these cells allow one a facile approach to obtaining and characterizing monoclonal antibodies against differentiation-specific antigens. Use of hybrid cells derived from HeLa X differentiated cell fusions as immunogens should prove to be a general method for identifying differentiation-specific antigens from a variety of differentiated cell types.

Animals

Ischemic oculopathy.

A 58-year-old woman had unilateral visual loss, anterior uveitis, rubeosis, and glaucoma. She subsequently was found to have a complete occlusion of the internal carotid on the same side. The clinician is reminded to consider a diagnosis of carotid insufficiency in elderly patients with anterior uveitis or rubeosis of obscure origin.

Arterial Occlusive Diseases

An outbreak of Pseudomonas mastitis in dairy cows.

An outbreak of mastitis in a dairy herd is described in which the causative organism was Pseudomonas aeruginosa. Cases occurred either in dry cows or in animals which had very recently calved. The fact that all four quarters were involved is a very strong indication that the bacteria had been introduced in the dry cow therapy.

Animals

The mechanical properties of bone tissue in children.

Specimens of femoral cortical bone from eighteen subjects between two and forty-eight years old were loaded in bending. Compared with the bone of adults, that of children had a lower modulus of elasticity, a lower bending strength, and a lower ash content. However, the children's bone deflected more and absorbed more energy before breaking. It also tended to absorb more energy after fracture had started. The typical greenstick fracture surface of many specimens of children's bone requires more energy for its production than the relatively smooth surface of adult specimens.

Adolescent