Pharmacodynamic response and inhibition of growth of human tumor xenografts by the novel histone deacetylase inhibitor PXD101.

Histone acetylation has a central role in the control of gene expression, influencing transcriptional control of many genes, including tumor suppressor genes. PXD101 is a novel hydroxamate-type inhibitor of histone deacetylase activity that inhibits histone deacetylase activity in HeLa cell extracts with an IC(50) of 27 nM and induces a concentration-dependent (0.2-5 micro M) increase in acetylation of histone H4 in tumor cell lines.

Alchemix: a novel alkylating anthraquinone with potent activity against anthracycline- and cisplatin-resistant ovarian cancer.

Chloroethylaminoanthraquinones are described with intercalating and alkylating capacity that potentially covalently cross-link topoisomerase II (topo II) to DNA. These compounds have potent cytotoxic activity (IC(50) = 0.9-7.

CD83-positive dendritic cells are present in occasional perivascular cuffs in multiple sclerosis lesions.

Multiple sclerosis (MS) has a wide spectrum of clinical courses, characterized by multifocal central nervous system (CNS) damage, postulated to be mediated by CNS antigen-specific T cells. Dendritic cells (DC), the most potent antigen-presenting cell, play a pivotal role in the decision between T-cell activation or anergy. Monoclonal antibodies to CD1a (immature DC) and CD83 (mature DC) were used to screen lesions with evidence of recent demyelinating activity and chronic plaque and normal appearing white matter (NAWM) tissue sections from 12 MS cases by immunocytochemistry.

The isolation and use of iron-oxidizing, moderately thermophilic acidophiles from the Collie coal mine for the generation of ferric iron leaching solution.

Moderately thermophilic, iron-oxidizing acidophiles were enriched from coal collected from an open-cut mine in Collie, Western Australia. Iron-oxidizers were enriched in fluidized-bed reactors (FBR) at 60 degrees C and 70 degrees C; and iron-oxidation rates were determined. Ferrous iron oxidation by the microbiota in the original coal material was inhibited above 63;C.

Kinetic and phylogenetic characterization of an anaerobic dechlorinating microbial community.

The reductive dechlorination (RD) of tetrachloroethene (PCE) to vinyl chloride (VC) and, to a lesser extent, to ethene (ETH) by an anaerobic microbial community has been investigated by studying the processes and kinetics of the main physiological components of the consortium. Molecular hydrogen, produced by methanol-utilizing acetogens, was the electron donor for the PCE RD to VC and ETH without forming any appreciable amount of other chlorinated intermediates and in the near absence of methanogenic activity. The microbial community structure of the consortium was investigated by preparing a 16S rDNA clone library and by fluorescence in situ hybridization (FISH).

Experience with hospice: reflections from third-year medical students.

Nationally, there is a growing emphasis on experiential education and an interest in palliative care for health professionals. Hospice visits were added to the family medicine community rotation for third-year medical students to provide them with first-hand exposure to the hospice experience. Seven significant themes emerged from the students' reflection papers: (1) the value of hospice and the supportive role of the hospice team, (2) the value of empathy, (3) the distinction between acceptance and resignation, (4) the changing face of hope, (5) an understanding of death as a natural event, (6) the quality of family caregiving, and (7) the role of the physician in caring for the dying.

Cultural factors in preventive care: African-Americans.

In summary, the implications for healthcare practitioners in caring for African American patients in a culturally sensitive manner include: Gaining trust, and understanding the historical distrust of the health care system Understanding and employing the kinship web in decisions regarding screening and treatment Involving the church in developing and delivering prevention and care messages Asking patients about the meaning of words or phrases Asking patients about the use of alternative medicines and herbs Tailoring messages about prevention to depictions of real life situations Paying attention to body language and other nonverbal communication.

Transfection of lung cells in vitro and in vivo: effect of antioxidants and intraliposomal bFGF.

We hypothesized that constitutive formation of reactive oxygen species by respiratory cells is a barrier to gene transfer when liposome-DNA complexes are used, by contributing to rapid degradation of plasmid DNA. When plasmid DNA is complexed to liposomes it is protected against H(2)O(2)-mediated degradation but not that mediated by the hydroxyl radical. Treatment of distal rat fetal lung epithelial cells (RFL(19)Ep) with the vitamin E analog Trolox (50 microM) reduced intracellular plasmid degradation.

The syndromic approach to treatment of sexually transmitted diseases in low-income countries: issues, challenges, and future directions.

Background: Sexually transmitted diseases (STDs) are a major cause of adult morbidity worldwide. In 1991, the World Health Organization (WHO) introduced the concept of the "syndromic approach" to managing sexually transmitted diseases in low-income countries, however, there has been some controversy regarding the ongoing use of this approach.

Objectives: (1) To understand the use of the syndromic approach to managing sexually transmitted diseases in low-income countries, and to determine if evidence supports its continued use.

Cost-effectiveness of eformoterol Turbohaler versus salmeterol Accuhaler in children with symptomatic asthma.

We conducted an economic evaluation in a UK setting based on a 12-week prospective randomized open-label parallel-group comparison of eformoterol Turbohaler 12 microg b. i.d.

Abnormal endothelial tight junctions in active lesions and normal-appearing white matter in multiple sclerosis.

Blood-brain barrier (BBB) breakdown, demonstrable in vivo by enhanced MRI is characteristic of new and expanding inflammatory lesions in relapsing-remitting and chronic progressive multiple sclerosis (MS). Subtle leakage may also occur in primary progressive MS. However, the anatomical route(s) of BBB leakage have not been demonstrated.

Cutaneous melanin density of Caucasians measured by spectrophotometry and risk of malignant melanoma, basal cell carcinoma, and squamous cell carcinoma of the skin.

Recent advances have enabled quite accurate estimation by spectrophotometry of the density of cutaneous melanin. The relation between skin cancers and this objective measure of skin phenotype is examined here. For this purpose, a population-based case-control study of subjects aged 20-59 years of northern European ancestry was conducted in Tasmania, Australia.

Infection of human oligodendroglioma cells by a recombinant measles virus expressing enhanced green fluorescent protein.

One of the hallmarks of the human CNS disease subacute sclerosing panencephalitis (SSPE) is a high level of measles virus (MV) infection of oligodendrocytes. It is therefore surprising that there is only one previous report of MV infection of rat oligodendrocytes in culture and no reports of human oligodendrocyte infection in culture. In an attempt to develop a model system to study MV infection of oligodendrocytes, time-lapse confocal microscopy, immunocytochemistry, and electron microscopy (EM) were used to study infection of the human oligodendroglioma cell line, MO3.

Exposures and outcomes of children with urticaria seen in a pediatric practice-based research network: a case-control study.

Objectives: (1) To determine the duration, outcome, and associated findings of urticaria in children seen by general pediatricians; (2) to compare the exposure to foods, medications, insect stings or bites, and the presence of other symptoms in children with urticaria with controls; (3) to determine general pediatricians' management of urticaria.

Design: Case-control.

Participants: Children with urticaria seen by Utah Pediatric Practice Based Research Network members between August 1, 1999, and August 31, 2000.

Microbial populations associated with treatment of an industrial dye effluent in an anaerobic baffled reactor.

Fluorescent in situ hybridization (FISH) using 16S and 23S rRNA-targeted probes together with construction of an archaeal 16S ribosomal DNA (rDNA) clone library was used to characterize the microbial populations of an anaerobic baffled reactor successfully treating industrial dye waste. Wastewater produced during the manufacture of food dyes containing several different azo and other dye compounds was decolorized and degraded under sulfidogenic and methanogenic conditions. Use of molecular methods to describe microbial populations showed that a diverse group of Bacteria and Archaea was involved in this treatment process.

In vitro and in vivo reversal of P-glycoprotein-mediated multidrug resistance by a novel potent modulator, XR9576.

The overexpression of P-glycoprotein (P-gp) on the surface of tumor cells causes multidrug resistance (MDR). This protein acts as an energy-dependent drug efflux pump reducing the intracellular concentration of structurally unrelated drugs. Modulators of P-gp function can restore the sensitivity of MDR cells to such drugs.

Economic impact of tibolone compared with continuous-combined hormone replacement therapy. In the management of postmenopausal women with climacteric symptoms in the UK.

Objective: To estimate the economic impact of using tibolone 2.5 mg compared with 17 beta-estradiol 2 mg/norethisterone acetate 1 mg (E2/NETA) in postmenopausal women with climacteric symptoms.

Design And Setting: This was a modelling study performed from the perspective of the UK's National Health Service (NHS).

Reversal of drug resistance in human tumor xenografts by 2'-deoxy-5-azacytidine-induced demethylation of the hMLH1 gene promoter.

Loss of DNA mismatch repair because of hypermethylation of the hMLH1 gene promoter occurs at a high frequency in a number of human tumors. A role for loss of mismatch repair (MMR) in resistance to a number of clinically important anticancer drugs has been shown. We have investigated whether the demethylating agent 2'-deoxy-5-azacytidine (DAC) can be used in vivo to sensitize MMR-deficient, drug-resistant ovarian (A2780/cp70) and colon (SW48) tumor xenografts that are MLH1 negative because of gene promoter hypermethylation.

Targeting transgene expression to airway epithelia and submucosal glands, prominent sites of human CFTR expression.

Targeting therapeutic gene expression to disease-affected tissues is an essential component of effective and safe gene therapy. After birth, CFTR gene expression in human lungs is localized predominantly in the epithelial cells lining the upper airways, especially in the ducts and serous tubules of the submucosal glands. We have developed a K18 expression cassette, based on the DNA control elements of the human cytokeratin 18 gene.

A human epithelium-specific vector optimized in rat pneumocytes for lung gene therapy.

Gene therapy vectors based on mammalian promoters offer the potential for increased cell specificity and may be less susceptible than viral promoters to transcription attenuation by host cytokines. The human cytokeratin 18 (K18) gene is naturally expressed in the lung epithelia, a target site for gene therapies to treat certain genetic pediatric lung diseases. Our original vector based on the promoter and 5' control elements of K18 offered excellent epithelial cell specificity but relatively low expression levels compared with viral promoters.

Annual cost of erectile dysfunction to UK Society.

Objective: The objective of this study was to estimate the annual socioeconomic burden imposed by erectile dysfunction (ED) on UK society.

Design And Setting: Health service resource use attributable to ED during 1997/1998 was obtained from appropriate databases and a panel of 22 hospital specialists comprising urologists, genito-urinary physicians, diabetologists and sexual health physicians. National unit resource costs at 1996/1997 prices were applied to the resource use data to estimate the annual National Health Service (NHS) cost of managing ED.

Preliminary description of lesions in juvenile largemouth bass injected with largemouth bass virus.

Juvenile largemouth bass Micropterus salmoides were intraperitoneally injected with largemouth bass virus (LMBV), a member of the genus Ranavirus, family Iridoviridae. Moribund fish which had been injected with 10(6.2) tissue culture infectious doses, 50% endpoint (TCID50), were sampled 4 d after injection; other largemouth bass injected with this dose died between 3 and 5 d after injection.