Gamma-irradiation of lyophilised wound healing wafers.

Lyophilised wafers are being developed as drug delivery systems that can be applied directly to the surface of suppurating wounds. They are produced by the freeze-drying of polymer solutions and gels. This study investigates the possibility of sterilising these glassy, solid dosage forms with gamma-irradiation and determining the rheological properties of rehydrated wafers post-irradiation.

High speed detection of circulating tumor cells.

Epithelial tumor cells circulate in peripheral blood at ultra-low concentrations in cancer patients. We have developed an instrument capable of rapid and accurate detection of rare cells in circulation utilizing fiber-optic array scanning technology (FAST). The FAST cytometer can locate immunofluorescently labeled rare cells on glass substrates at scan rates 500 times faster than conventional automated digital microscopy.

TREM2, a DAP12-associated receptor, regulates osteoclast differentiation and function.

Unlabelled: Deficiency of the signaling adapter protein DAP12 or its associated receptor TREM2 is associated with abnormal OC development in humans. Here we examine the role of TREM2 in mouse OC development and function, including migration and resorption in vitro. These results provide new evidence that TREM2 regulates OC function independent of its effects on multinucleated OC differentiation.

Role of ITAM-containing adapter proteins and their receptors in the immune system and bone.

The immunoreceptor tyrosine-based activation motif (ITAM) is a highly conserved region in the cytoplasmic domain of signaling chains and receptors and is a critical mediator of intracellular signals. ITAM-mediated signals depend on the Syk or zeta-associated protein of 70 kDa tyrosine kinases, and ITAM signaling is required for the differentiation and function of B and T cells in adaptive immunity. ITAM-dependent receptors also regulate the function of innate immune cells, including natural killer cells, and myeloid-derived cells such as macrophages, neutrophils, dendritic cells, and mast cells.

A streamlined platform for high-content functional proteomics of primary human specimens.

Achieving information content of satisfactory breadth and depth remains a formidable challenge for proteomics. This problem is particularly relevant to the study of primary human specimens, such as tumor biopsies, which are heterogeneous and of finite quantity. Here we present a functional proteomics strategy that unites the activity-based protein profiling and multidimensional protein identification technologies (ABPP-MudPIT) for the streamlined analysis of human samples.

The ketogenic diet in refractory childhood epilepsy.

Objective: To report the efficacy and tolerability of the ketogenic diet (KD) in refractory paediatric epilepsy.

Methods: Twenty-six consecutive children were treated with the classical KD from 1996 to 2001. The epilepsy syndromes included symptomatic generalized epilepsy (15), idiopathic generalized epilepsy (4), symptomatic partial epilepsy (1) and unclassified epilepsy (6).

Mitochondrial mediated thimerosal-induced apoptosis in a human neuroblastoma cell line (SK-N-SH).

Environmental exposure to mercurials continues to be a public health issue due to their deleterious effects on immune, renal and neurological function. Recently the safety of thimerosal, an ethyl mercury-containing preservative used in vaccines, has been questioned due to exposure of infants during immunization. Mercurials have been reported to cause apoptosis in cultured neurons; however, the signaling pathways resulting in cell death have not been well characterized.

Mixed-metal cluster chemistry. 28. Core enlargement of tungsten-iridium clusters with alkynyl, ethyndiyl, and butadiyndiyl reagents.

Reaction of [WIr3(mu-CO)3(CO)8(eta-C5Me5)] (1c) with [W(C[triple bond]CPh)(CO)3(eta-C5H5)] afforded the edge-bridged tetrahedral cluster [W2Ir3(mu4-eta2-C2Ph)(mu-CO)(CO)9(eta-C5H5)(eta-C5Me5)] (3) and the edge-bridged trigonal-bipyramidal cluster [W3Ir3(mu4-eta2-C2Ph)(mu-eta2-C=CHPh)(Cl)(CO)8(eta-C5Me5)(eta-C5H5)2] (4) in poor to fair yield. Cluster 3 forms by insertion of [W(C[triple bond]CPh)(CO)3(eta-C5H5)] into Ir-Ir and W-Ir bonds, accompanied by a change in coordination mode from a terminally bonded alkynyl to a mu4-eta2 alkynyl ligand. Cluster 4 contains an alkynyl ligand interacting with two iridium atoms and two tungsten atoms in a mu4-eta2 fashion, as well as a vinylidene ligand bridging a W-W bond.

IGF-I and IGFBP-3 polymorphisms and risk of prostate cancer.

Background: Insulin-like growth factor-I (IGF-I) is a potent mitogen for both normal and malignant prostate epithelial cells. The majority of circulating IGF-I is bound in a complex with IGF binding protein-3 (IGFBP-3), which in turn limits IGF-I bioavailability. Multiple studies suggest that higher IGF-I and/or lower IGFBP-3 serum levels are positively associated with prostate cancer risk.

Lyophilised wafers as a drug delivery system for wound healing containing methylcellulose as a viscosity modifier.

Lyophilised wafers have potential as drug delivery systems for suppurating wounds. A dual series of wafers made from low molecular weight sodium alginate (SA) and xanthan gum (XG) respectively, modified with high molecular weight methylcellulose (MC) were produced. The swelling and flow properties of these wafers on model suppurating surfaces were both qualitatively and quantitatively investigated.

Mice lacking the integrin beta5 subunit have accelerated osteoclast maturation and increased activity in the estrogen-deficient state.

Unlabelled: Integrin alphavbeta5 is expressed on osteoclast precursors and is capable of recognizing the same amino acid motif as alphavbeta3. Three-month-old beta5(-/-) female OVX mice had increased osteoclastogenesis ex vivo, and microCT assessment of trabecular bone volume was 53% lower than WT-OVX animals. These preliminary data suggest alphavbeta5 integrin's presence on osteoclast precursors may inhibit of osteoclast formation.

Ruthenium bipyridyl compounds with two terminal alkynyl ligands.

Compounds of the form Ru(X2bipy)(PPh3)2(-C triple bond CC6H4NO2-p)2(X2bipy = 4,4'-X(2)-2,2'-bipyridine, X = Me 3a, Br 3b, I 3c) have been synthesised from the mono-alkynyl precursors Ru(X2bipy)(PPh3)2(-C triple bond CC6H4NO2-p)Cl (X = Me 2a, Br 2b, I 2c); the former are the first ruthenium bis-alkynyl compounds that also contain a bipyridyl ligand. Spectroelectrochemical investigation of 3a shows that the metal is readily oxidised to form the ruthenium(III) compound 3a+, and will also undergo a single-electron reduction at each nitro group to form 3a2-. ESR and UV/visible spectra of these redox congeners are presented.

Dispersion of the third-order nonlinear optical properties of an organometallic dendrimer(1).

The dispersion of cubic nonlinearity in the organometallic dendrimer 1,3,5-(3,5-{trans-[(dppe)2(4-O2NC6H4CC)RuCC]}2C6H3CCC6H4-4-CC)3C6H3 can be understood in terms of an interplay of two-photon absorption and absorption saturation. Simple dispersion relations reproduce the behavior of both the real and imaginary components of the hyperpolarizability.

Carcinoma and stromal enzyme activity profiles associated with breast tumor growth in vivo.

Cancer research depends on the use of human cell lines for both the in vitro (culture) and in vivo (xenograft) analysis of tumor progression and treatment. However, the extent to which cultured preparations of human cancer lines display similar properties in vivo, where important host factors may influence tumor biology, remains unclear. Here, we address this question by conducting a functional proteomic analysis of the human breast cancer line MDA-MB-231 grown in culture and as orthotopic xenograft tumors in the mammary fad pad of immunodeficient mice.

Activity-based probes for the proteomic profiling of metalloproteases.

Metalloproteases (MPs) are a large and diverse class of enzymes implicated in numerous physiological and pathological processes, including tissue remodeling, peptide hormone processing, and cancer. MPs are tightly regulated by multiple posttranslational mechanisms in vivo, hindering their functional analysis by conventional genomic and proteomic methods. Here we describe a general strategy for creating activity-based proteomic probes for MPs by coupling a zinc-chelating hydroxamate to a benzophenone photocrosslinker, which promote selective binding and modification of MP active sites, respectively.

Lack of antenatal care in far north Queensland.

Objective: To examine reasons for women not accessing antenatal care, and subsequent pregnancy outcomes for this group of women.

Design: Retrospective observational study between 1992 and 2001.

Setting: Large public provincial referral obstetric unit.

The immunomodulatory adapter proteins DAP12 and Fc receptor gamma-chain (FcRgamma) regulate development of functional osteoclasts through the Syk tyrosine kinase.

Osteoclasts, the only bone-resorbing cells, are central to the pathogenesis of osteoporosis, yet their development and regulation are incompletely understood. Multiple receptors of the immune system use a common signaling paradigm whereby phosphorylated immunoreceptor tyrosine-based activation motifs (ITAMs) within receptor-associated adapter proteins recruit the Syk tyrosine kinase. Here we demonstrate that a similar mechanism is required for development of functional osteoclasts.

The signaling adapter protein DAP12 regulates multinucleation during osteoclast development.

Unlabelled: Deficiency of the signaling adapter protein DAP12 is associated with bony abnormalities in both mice and humans. We identify specific DAP12-associated receptors expressed by osteoclasts and examine function of DAP12 in murine osteoclasts in vivo and in vitro. These data show a new role for DAP12 signaling in regulating formation of multinucleated osteoclasts.

CMRF-35-like molecule-1, a novel mouse myeloid receptor, can inhibit osteoclast formation.

By homology to triggering receptor expressed by myeloid cells-2, we screened the mouse expressed sequence tag database and isolated a new single Ig domain receptor, which we have expressed and characterized. The receptor is most similar in sequence to the human CMRF-35 receptor, and thus we have named it CMRF-35-like molecule (CLM)-1. By screening the mouse genome, we determined that CLM-1 was part of a multigene family located on a small segment of mouse chromosome 11.

Is grand multiparity an independent predictor of pregnancy risk? A retrospective observational study.

Objective: To determine whether high maternal parity has any effect on pregnancy outcome independent of other maternal characteristics.

Design And Setting: Retrospective observational study using the database of a referral obstetric unit in a 280-bed regional hospital in far north Queensland.

Participants: All 15 908 women who had singleton births between 1992 and 2001, comprising 653 women with grand multiparity (>or= 5 previous births at gestation >or= 20 weeks) and 15 255 women with lower parity.

Megestrol acetate in pediatric oncology patients may lead to severe, symptomatic adrenal suppression.

Background: Despite the widespread use of megestrol acetate (MA) among a growing number of pediatric oncology departments, there is only one published study on the use of MA in children with malignant disease. The objectives of the current study were to examine the effect of MA in improving the nutritional status of children with malignant disease and to describe and consider the implications of MA-associated adrenal suppression that was found consistently.

Methods: Medical records of 19 children with malignant disease who were treated with MA were reviewed.

Organometallic complexes for nonlinear optics. 30.1 electrochromic linear and nonlinear optical properties of alkynylbis(diphosphine)ruthenium complexes.

A combination of cyclic voltammetry, UV-vis-NIR spectroelectrochemistry, time-dependent density functional theory (TD-DFT), and Z-scan measurements employing a modified optically transparent thin-layer electrochemical (OTTLE) cell has been used to identify and assign intense transitions of metal alkynyl complexes at technologically important wavelengths in the oxidized state and to utilize these transitions to demonstrate a facile electrochromic switching of optical nonlinearity. Cyclic voltammetric data for the ruthenium(II) complexes trans-[RuXY(dppe)(2)] [dppe = 1,2-bis(diphenylphosphino)ethane, X = Cl, Y = Cl (1), Ctbd1;CPh (2), 4-Ctbd1;CC(6)H(4)Ctbd1;CPh (3); X = Ctbd1;CPh, Y = Ctbd1;CPh (4), 4-Ctbd1;CC(6)H(4)Ctbd1;CPh (5)] show a quasi-reversible oxidation at 0.50-0.