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Biomedical subjects

G Brooke

Publications and source records attributed to G Brooke.

18 recordsLinked to original sources
PubMed2004

Gliotoxin is a dual inhibitor of farnesyltransferase and geranylgeranyltransferase I with antitumor activity against breast cancer in vivo.

Gliotoxin is a natural mycotoxin with immunosuppressive and antimicrobial activity. Inhibition of farnesyltransferase (IC50 80 microM) and geranylgeranyltransferase I (IC50 17 microM) stimulated interest in the potential antitumor activity of this epidithiodioxopiperazine. Gliotoxin inhibited proliferation of six breast cancer cell lines in culture with mean +/- SD IC50 289 +/- 328 microM (range 38-985 microM); intracellular farnesylation of Lamin B and geranylgeranylation of Rap1A were inhibited in a dose-dependent manner. In randomized controlled studies using the N-methyl-N-nitrosourea rat mammary carcinoma model, gliotoxin had pronounced antitumor activity in vitro and little systemic toxicity when administered to 10 animals at 10 mg/kg by subcutaneous injection weekly for 4 wk compared with 10 controls. Single doses up to 25 mg/kg were well tolerated. The present studies confirm that gliotoxin is a dual inhibitor of farnesyltransferase and geranylgeranyltransferase I with pronounced antitumor activity and favorable toxicity profile against breast cancer in vitro and in vivo.

Alkyl and Aryl Transferases↗
PubMed1998

Deploying a new model for clinical information delivery.

Information is a dynamic, potentially high-value resource that institutions can use to achieve superior performance. The myriad of advanced information technology projects, however, delivers to the institution's clinical and business processes unpredictable deluges of information objects, both paper and electronic, that may add little value to the processes. Also, because the information arrival is often a trigger for work steps, its illogical arrival may actually dilute productivity and quality. The article describes an information distribution engine in use at a large hospital in the southwestern United States that allows remotely located recipients to define individualized rules for controlling the subset of diverse information that they receive, select its transmission and display media, and choreograph the sequence and timing of its arrival at their desktops.

Attitude to Computers↗
PubMed1993

Operons in C. elegans: polycistronic mRNA precursors are processed by trans-splicing of SL2 to downstream coding regions.

The mRNAs of six C. elegans genes are known to be trans-spliced to SL2. We report here that a similarly oriented gene is located 100-300 bp upstream of each. We present evidence that the genes in these clusters are cotranscribed and downstream mRNAs are formed by cleavage at the polyadenylation site and trans-splicing. From one three-gene cluster we isolated cDNA clones representing both polycistronic RNAs and mRNAs polyadenylated at the free 3' end created by trans-splicing, suggesting that polycistronic RNAs can be processed by trans-splicing. Several experiments indicate that SL2 trans-splicing is a consequence of a gene's downstream location in an operon. In particular, when an SL1-accepting gene was moved to a downstream location, its mRNA was trans-spliced largely to SL2. The possible regulatory significance of cotranscription of C. elegans genes is discussed.

Animals↗
PubMed1992

Crystallization of the exo(1,3)-beta-glucanase from Candida albicans.

An exoglucanase, with specificity for beta (1,3) linkages, from the cell wall of Candida albicans has been crystallized by the hanging drop method in the presence of polyethylene glycol 8000. The crystals, which diffract to better than 1.9 A resolution, belong to the orthorhombic space group P212121 with cell constants a = 60.2 A, b = 65.2 A, c = 96.5 A and with one molecule in the asymmetric unit.

Candida albicans↗
PubMed1988

Immunization against foot-and-mouth disease with synthetic peptides representing the C-terminal region of VP1.

Foot-and-mouth disease virus challenge experiments in guinea-pigs and immunoassays with a range of peptides equivalent to either or both of the sequences 141 to 158 and 200 to 213 of VP1 showed the most effective structure, in terms of protection, to be one in which both 'sites' were present with a minimum of additional amino acids. An 80 residue peptide comprising amino acids 134 to 213 was considerably less effective than 40 or 45 residue peptides. The major site for the induction of protection was deduced to be in the region 141 to 158. Thus, protection with the 40 or 45 residue peptide did not appear to be due to the presence of antibody directed solely to the 200 to 213 sequence. Finally, induction of antibody to the latter site appeared to be dependent on both the size of the peptide and the disposition of 'sites' within it.

Animals↗
PubMed1986

Protection of cattle against foot-and-mouth disease by a synthetic peptide.

A chemically synthesized peptide consisting essentially of two separate regions (residues 141 to 158 and 200 to 213) of a virus coat protein (VP1) from the O1 Kaufbeuren strain of foot-and-mouth disease virus was prepared free of any carrier protein. It elicited high levels of neutralizing antibody and protected cattle against intradermolingual challenge by inoculation with infectious virus. Comparative evaluation of this peptide with a single-site peptide (residues 141 to 158) in guinea pigs suggests the importance of the VP1 carboxyl terminal residues in enhancing the protective response.

Animals↗
PubMed1984

The synovial response to intra-articular acrylic cement particles in guinea pigs.

The histology and cytology of the tissue response to intra-articular insertion of particles of acrylic bone cement containing barium sulphate has been studied in the guinea pig knee joint. Following insertion of the acrylic, fibrinous debris admixed with particles became adherent to the synovial membrane. Cell proliferation at the interface between the debris and the synovial tissue engulfed the debris, and a new layer of intimal lining cells formed over its surface. This process led to incorporation of the particles into vascularized subintimal tissue. The response to subintimal acrylic cement particles was by multinucleate giant cells (macrophage polykaryons), macrophages and fibroblasts, with a variable amount of intermingled fibrosis. After incorporation was complete, the long-term (3 months to 1 year) subintimal response acquired a basically stable histological appearance amongst which no zones of tissue necrosis were found. However, in some instances it did contain foci of neutrophil infiltration, and it is possible that such foci are a reaction to minor episodes of cell damage.

Animals↗
PubMed1983

The synovial response to intra-articular Co-Cr-Mo particles in guinea pigs.

The histology and cytology of the tissue response to an intra-articular insertion of Co-Cr-Mo particles has been studied in the guinea pig knee joint. Following insertion, particles became incorporated into synovial tissue in two ways: (A) by incorporation in the intimal (surface) cell layer; (B) by growth of granulation tissue into metal-containing debris initially adherent to the synovial surface, leading to its incorporation in the subintimal tissue (i.e. beneath the surface), with subintimal fibrosis. Small particles of Co-Cr-Mo were phagocytosed by intimal cells, macrophages, multinucleate giant cells (macrophage polykaryons) and fibroblasts; large particles remained extracellular. Metal particles persisted in the synovial fluid, intimal cell layer and subintimal tissue for many months after metal insertion. As an unexpected finding, no zones of tissue necrosis were observed in the long-term (3 months to 1 year) response to Co-Cr-Mo particles incorporated in subintimal tissue. Lymphatic transport of metal particles from the knee area to inguinal lymph nodes was observed.

Animals↗
PubMed1982

The tissue response to acrylic particles implanted in animal muscle.

The histology and ultrastructure of the tissue response to particles of acrylic bone cement have been studied in rat and guinea pig muscle. Initially the implant formed an avascular zone of extracellular particles which rapidly became infiltrated by neutrophils. The particle zone was then progressively incorporated into new tissue by an ingrowth of small blood vessels accompanied by macrophages, multinucleate giant cells and some fibroblasts'. Acrylic particles were phagocytosed into macrophages and giant cells. The giant cells often had a characteristic ring form. After vascularization and incorporation was complete, the macrophage and giant cell accumulation acquired a basically stable histological appearance over study periods of up to 2 yrs. A large majority of these cells appeared viable, and no zones of tissue necrosis were seen. However, occasional individual shrunken necrotic cells of unidentified origin and occasional individual tiny foci of nuclear debris were sometimes observed, sparsely distributed amongst the response, and a minor degree of neutrophil reaction was noted amongst some, but by no means all, of the long-term implants. The interpretation of morphological assessment for tissue toxicity is discussed. No evidence was obtained for the induction of cell-mediated hypersensitivity or of neoplasia by the cement particle preparations used.

Acrylic Resins↗
PubMed1980

Estate management: when reality stifles ambition.

Health service buildings and lands make up an estate which must be managed in such a way that the future does not suffer from the neglect of the present. Looking to the NHS as it is likely to be in the 1980s, Gordon Brooke, regional works officer, Mersey RHA, suggests an end to a system in which capital is a 'free good' and districts under financial pressure have little incentive to preserve the value of their estates.

Capital Financing↗