Elevation of XPA protein level in testis tumor cells without increasing resistance to cisplatin or UV radiation.

Most testicular germ cell tumors are curable using cisplatin-based chemotherapy, and cell lines from these tumors are unusually sensitive to cisplatin and other DNA-damaging agents. It has been suggested that this might be caused by a lower-than normal nucleotide excision repair (NER) activity. Previous studies found that cell lines from testicular germ cell tumors have on average about one-third the level of the NER protein XPA in comparison to cell lines from other tumors.

Interferon-gamma reduces cell surface expression of annexin 2 and suppresses the invasive capacity of prostate cancer cells.

The effect of interferon-gamma (IFNgamma) treatment on cell surface protein expression was studied in the human prostate cancer cell line 1542CP3TX. IFNgamma increased both the number and abundance of proteins in membrane fractions. In contrast, the expression of annexin 2 and its binding partner p11 decreased by 4-fold after 24 h of exposure, with the remaining anx2(t) complexes localized to lipid rafts.

The candidate genes TAF5L, TCF7, PDCD1, IL6 and ICAM1 cannot be excluded from having effects in type 1 diabetes.

Background: As genes associated with immune-mediated diseases have an increased prior probability of being associated with other immune-mediated diseases, we tested three such genes, IL23R, IRF5 and CD40, for an association with type 1 diabetes. In addition, we tested seven genes, TAF5L, PDCD1, TCF7, IL12B, IL6, ICAM1 and TBX21, with published marginal or inconsistent evidence of an association with type 1 diabetes.

Methods: We genotyped reported polymorphisms of the ten genes, nonsynonymous SNPs (nsSNPs) and, for the IL12B and IL6 regions, tag SNPs in up to 7,888 case, 8,858 control and 3,142 parent-child trio samples.

Allelic imbalance at 13q14.2 approximately q14.3 in localized prostate cancer is associated with early biochemical relapse.

Allelic imbalance (AI), particularly at chromosomes 8p, 10q, and 13q, is the most frequently observed genetic change in sporadic prostate cancer. AI at these sites may inactivate tumor suppressor genes that regulate normal cell growth. To establish the relationship between AI and progression, we analyzed loci on 8p, 10q, and 13q14 in archival prostate tumors matched for Gleason grade, pre-operative prostate-specific antigen levels, and pathologic stage, and they were paired on the basis of relapse status after 3 years.

Plexin-B1 mutations in prostate cancer.

Semaphorins are a large class of secreted or membrane-associated proteins that act as chemotactic cues for cell movement via their transmembrane receptors, plexins. We hypothesized that the function of the semaphorin signaling pathway in the control of cell migration could be harnessed by cancer cells during invasion and metastasis. We now report 13 somatic missense mutations in the cytoplasmic domain of the Plexin-B1 gene.

Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A.

The major histocompatibility complex (MHC) on chromosome 6 is associated with susceptibility to more common diseases than any other region of the human genome, including almost all disorders classified as autoimmune. In type 1 diabetes the major genetic susceptibility determinants have been mapped to the MHC class II genes HLA-DQB1 and HLA-DRB1 (refs 1-3), but these genes cannot completely explain the association between type 1 diabetes and the MHC region. Owing to the region's extreme gene density, the multiplicity of disease-associated alleles, strong associations between alleles, limited genotyping capability, and inadequate statistical approaches and sample sizes, which, and how many, loci within the MHC determine susceptibility remains unclear.

Investigation of the terminal P4 domain in a series of D-phenylglycinamide-based factor Xa inhibitors.

Several P4 domain derivatives of the general d-phenylglycinamide-based scaffold (2) were synthesized and evaluated for their ability to bind to the serine protease factor Xa. Some of the more potent compounds were evaluated for their anticoagulant effects in vitro. A select subset containing various P1 indole constructs was further evaluated for their pharmacokinetic properties after oral administration to rats.

Systematic literature review of oral hygiene practices for intensive care patients receiving mechanical ventilation.

Background: Oropharyngeal colonization with pathogenic organisms contributes to the development of ventilator-associated pneumonia in intensive care units. Although considered basic and potentially nonessential nursing care, oral hygiene has been proposed as a key intervention for reducing ventilator-associated pneumonia. Nevertheless, evidence from randomized controlled trials that could inform best practice is limited.

Changing medium and passaging cell lines.

Cell lines are widely used in biomedical research. This protocol describes the methods used routinely to change the medium and passage the cells. Medium changes keep the cells healthy by providing fresh nutrients, while cell passage or splitting is required to maintain cells in exponential growth.

Oral ciprofloxacin or trimethoprim reduces bacteriuria after flexible cystoscopy.

Objective: To report a large prospective, pragmatic, double-blind randomized controlled trial to determine whether oral prophylactic antibiotics reduce the risk of bacteriuria after flexible cystoscopy (FC), as up to 10% of patients develop urinary infection afterwards, with significant morbidity and costs for health services.

Patients And Methods: In all, 2481 patients were recruited into a three-arm placebo controlled trial and 2083 completed it. Patients were randomly assigned to one of three treatments; (i) placebo; (ii) one oral dose of trimethoprim (200 mg); or (iii) one oral dose of ciprofloxacin (500 mg), each administered 1 h before a FC under local anaesthetic.

Morbidity, mortality, and response to treatment by children in the United Kingdom and Ireland with perinatally acquired HIV infection during 1996-2006: planning for teenage and adult care.

Background: Recent evidence suggests that decreases in morbidity and mortality in cohorts of adults infected with human immunodeficiency virus (HIV) are showing signs of reversal. We describe changes over time in these characteristics and in the response to treatment among children in the United Kingdom and Ireland with perinatally acquired HIV infection, many of whom are now adolescents.

Methods: We analyzed prospective cohort data reported to the National Study of HIV in Pregnancy and Childhood (NSHPC) and the Collaborative HIV Paediatric Study.

Taking the sting out of examination review.

Since using this method, examination reviews have focused less on arguing for points and more on comprehending the material. Examination reviews are already stressful for students and faculty; posting the examination on the walls is a quick and easy way to facilitate a difficult task.

Anthranilamide inhibitors of factor Xa.

SAR about the B-ring of a series of N(2)-aroyl anthranilamide factor Xa (fXa) inhibitors is described. B-ring o-aminoalkylether and B-ring p-amine probes of the S1' and S4 sites, respectively, afforded picomolar fXa inhibitors that performed well in in vitro anticoagulation assays.

Clinical applications of expression profiling and proteomics in prostate cancer.

Expression profiling and proteomics have the potential to transform the management of prostate cancer, identifying new markers for screening, diagnosis, prognosis, monitoring and targets for therapy. Expression profiling has revealed that the majority of prostate cancers contain fusion genes resulting in the upregulation of ETS family transcription factors. New diagnostic markers to replace PSA are being actively sought using a variety of proteomic platforms.

Sequencing and association analysis of the type 1 diabetes-linked region on chromosome 10p12-q11.

Background: In an effort to locate susceptibility genes for type 1 diabetes (T1D) several genome-wide linkage scans have been undertaken. A chromosomal region designated IDDM10 retained genome-wide significance in a combined analysis of the main linkage scans. Here, we studied sequence polymorphisms in 23 Mb on chromosome 10p12-q11, including the putative IDDM10 region, to identify genes associated with T1D.

Hypomethylation of WNT5A, CRIP1 and S100P in prostate cancer.

Oligoarray analysis of a matched pair of prostate cancer and normal cell lines derived from the same radical prostatectomy specimen identified 113 candidate hypomethylated genes that were overexpressed in the cancer cells and contained CpG islands. Hypomethylation of wingless-related MMTV integration site 5A (WNT5A), S100 calcium-binding protein P (S100P) and cysteine-rich protein 1(CRIP1) was confirmed in the cancer cells by bisulfite sequencing. Treatment of the corresponding normal prostate epithelial cells 1542-NPTX with the DNA methyltransferase inhibitor 5-Aza-2'-deoxycytidine (5-aza-CdR) induced higher levels of mRNA expression and partial loss of methylation on these genes.

Taking phylogenetics beyond pattern analysis: can models of genome dynamics guide predictions about homoplasy in morphological and behavioral data sets?

Despite the considerable amount of interest in phylogeny reconstruction, patterns of homoplasy in morphological and behavioral data have received only limited attention to date, whereas the patterns of homoplasy in molecular data are relatively well understood. First, because the number of alternative molecular character states is strictly limited (particularly for nucleotide sequence data), higher rates of substitution generate higher levels of homoplasy. Second, depending on the relative proportions of constrained and unconstrained sites, each molecular data set has a time frame of applicability outside of which resolution becomes ambiguous.

A conditionally immortalized cell line model for the study of human prostatic epithelial cell differentiation.

In the normal human prostate, undifferentiated proliferative cells reside in the basal layer and give rise to luminal secretory cells. There are, however, few epithelial cell lines that have a basal cell phenotype and are able to differentiate. We set out to develop a cell line with these characteristics that would be suitable for the study of the early stages of prostate epithelial cell differentiation.

Phylogenetic relationships among the Lorisoidea as indicated by craniodental morphology and mitochondrial sequence data.

The phylogeny of the Afro-Asian Lorisoidea is controversial. While postcranial data attest strongly to the monophyly of the Lorisidae, most molecular analyses portray them as paraphyletic and group the Galagidae alternately with the Asian or African lorisids. One of the problems that has bedevilled phylogenetic analysis of the group in the past is the limited number of taxa sampled for both ingroup families.

Lack of torpor in free-ranging southern lesser galagos, Galago moholi: ecological and physiological considerations.

Studies investigating heterothermy under natural conditions are particularly scarce for tropical species. However, heterothermy patterns in tropical and subtropical environments often differ markedly from those observed in arctic and temperate species. The investigation of heterothermy in strepsirhine primates has focussed largely on the Malagasy cheirogaleids.

A composite molecular phylogeny of living lemuroid primates.

Lemuroid phylogeny is a source of lively debate among primatologists. Reconstructions based on morphological, physiological, behavioural and molecular data have yielded a diverse array of tree topologies with few nodes in common. In the last decade, molecular phylogenetic studies have grown in popularity, and a wide range of sequences has been brought to bear on the problem, but consensus has remained elusive.

Reconciling the origins of Africa, India and Madagascar with vertebrate dispersal scenarios.

Africa, India and Madagascar were once part of the supercontinent of Gondwana. This land mass began to fragment approx. 170 million years ago, and by 83 million years, all of the major components we recognize today were separated by tracts of water.

Changes in blood trihalomethane concentrations resulting from differences in water quality and water use activities.

Water disinfection is extremely important for the protection of public health; however, it also forms by-products, including trihalomethanes (THMs). Previous studies of health effects from disinfection by-products have lacked accurate methods to quantify exposure over time. As a first step in establishing a better system for exposure assessment, the authors investigated which household water use activities cause a significant increase in internal dose concentrations of THMs.

Human CD4+ CD25hi Foxp3+ regulatory T cells are derived by rapid turnover of memory populations in vivo.

While memory T cells are maintained by continuous turnover, it is not clear how human regulatory CD4+ CD45RO+ CD25hi Foxp3+ T lymphocyte populations persist throughout life. We therefore used deuterium labeling of cycling cells in vivo to determine whether these cells could be replenished by proliferation. We found that CD4+ CD45RO+ Foxp3+ CD25hi T lymphocytes were highly proliferative, with a doubling time of 8 days, compared with memory CD4+ CD45RO+ Foxp3- CD25- (24 days) or naive CD4+ CD45RA+ Foxp3- CD25- populations (199 days).