Biomedical subjects
Publications and source records attributed to P Warren.
From dengue to herpes and influenza to AIDS, the phytoestrogens that are present in many fruits and vegetables have been shown to exert anti-viral properties. Here we review the various different anti-viral mechanisms employed by phytoestrogens.
A prospective clinical trial was performed to assess the suitability of a new type of sterilisable, user-friendly radiation protection glove. In a preliminary trial, we showed that the dominant hand of the primary operating orthopaedic surgeon receives the highest dose of radiation. During a 4-month period, 98 procedures were done requiring the use of an image intensifier. The doses of radiation to the dominant hand of the operating surgeon were reduced to less than the doses of radiation to the non-dominant hand. The glove was sterilisable, user-friendly and accepted by the majority of surgeons. It offers greater than 90% attenuation of X-rays and is superior to all other scatter gloves on the market.
Explore the source record for details and available documents.
This paper describes some of the difficulties of hospital management and staff in meeting the UK National Health Service (NHS) Infection Control Standards designed to protect staff and patients against bacterial and viral infections. The majority of older hospitals and clinics in the NHS do not have the financial resources to provide sterilizing equipment that will meet new acceptable standards.
Human endogenous retrovirus HERV-K like-sequences have been implicated in certain cancers. We developed a novel multiplex RT-PCR system for HERV-K that yielded a 533 bp product together with a smaller sized product (319 bp) of the house keeping gene, histidyl tRNA synthetase (HtRNAS). The latter spanned an intron that also served to validate target cDNA. PCR amplicons of HERV-K and HtRNAS were visualised using a gel documentation system and the pixel intensity used to derive semi-quantitative levels of viral expression. Our data showed that HERV-K10 was significantly elevated in MCF-7 cells treated with estrogen. Interestingly, HERV-K expression was higher in MCF-7 cells selected with adriamycin. RT-PCR combined with Southern blotting also detected HERV-K from breast cancer tissue using laser capture microscopy. This study highlights the presence of HERV-K in the breast cancer cell lines MCF-7 and MCF-7 ADR and confirms HERV-K10 transcripts in the cell line T47D. We believe this study to be a novel approach in determining levels of HERV-K expression and for detecting this virus in cancer cell lines and tissues.
All modern computers are designed using the 'von Neumann' architecture and built using silicon transistor technology. Both architecture and technology have been remarkably successful. Yet there are a range of problems for which this conventional architecture is not particularly well adapted, and new architectures are being proposed to solve these problems, in particular based on insight from nature. Transistor technology has enjoyed 50 years of continuing progress. However, the laws of physics dictate that within a relatively short time period this progress will come to an end. New technologies, based on molecular and biological sciences as well as quantum physics, are vying to replace silicon, or at least coexist with it and extend its capability. The paper describes these novel architectures and technologies, places them in the context of the kinds of problems they might help to solve, and predicts their possible manner and time of adoption. Finally it describes some key questions and research problems associated with their use.
Human endogenous retroviruses (HERVs) are a significant component of a wider family of retroelements that constitute part of the human genome. These viruses, perhaps representative of previous exogenous retroviral infection, have been integrated and passed through successive generations within the germ line. The retention of HERVs and isolated elements, such as long-terminal repeats, could have the potential to harm. In this review we describe HERVs within the context of the family of known transposable elements and survey these viruses in terms of superantigens and molecular mimics. It is entirely possible that these mechanisms provide the potential for undesired immune responses.
Recombinant antibodies are important tools for biomedical research and are increasingly being used as clinical diagnostic/therapeutic reagents. In this article, a background to humanized antibodies is given, together with details of the generation of antibody fragments--for example, single chain Fv fragments. Phage antibody fragments are fast becoming popular and can be generated by simple established methods of affinity enrichment from libraries derived from immune cells. Phage display methodology can also be used for the affinity enrichment of existing antibody fragments to provide a reagent with a higher affinity. Here, phage antibodies are demystified to provide a greater understanding of the potential of these reagents and to engage clinicians and biomedical scientists alike to think about potential applications in pathology and clinical settings.
Human endogenous retroviruses (HERVs) are a family of viruses within our genome with similarities to present day exogenous retroviruses. HERVs have been inherited by successive generations and it is possible that some have conferred biological benefits. However, several HERVs have been implicated in certain cancers and autoimmune diseases. This article demystifies these retroviruses by providing an insight into HERVs, their means of classification, and a synopsis of HERVs implicated in cancer and autoimmunity. Furthermore, the biological roles of HERVs are explored.
Comprehensive genomic analysis of the important human pathogen Staphylococcus aureus was achieved by a strategy involving antisense technology in a regulatable gene expression system. In addition to known essential genes, many genes of unknown or poorly defined biological function were identified. This methodology allowed gene function to be characterized in a comprehensive, defined set of conditionally growth-defective/lethal isogenic strains. Quantitative titration of the conditional growth effect was performed either in bacterial culture or in an animal model of infection. This genomic strategy offers an approach to the identification of staphylococcal gene products that could serve as targets for antibiotic discovery.
Prostate-specific membrane antigen (PSMA) is a trans-membrane protein specifically expressed in LNCaP cells, malignant human prostate tissues, and the surrounding neovasculature. PSMA is a unique exopeptidase with reactivity toward poly-gamma-glutamated folates. It can sequentially remove the poly-gamma-glutamyl termini. To target prostate tumor cells, a novel procytolytic peptide was designed with a backbone consisting of an amoebapore H3 domain modified by two gamma-linked glutamate residues at the epsilon-amino group of the COOH-terminal lysine residue. The strategy behind the design of this prolytic peptide was to inactivate the lytic amoebapore H3 peptide by replacing its functionally important COOH-terminal positive charge with negatively charged groups, which in turn might be selectively removed by the PSMA exopeptidase. This peptide exhibited little cytolytic activity toward PSMA-negative cells, such as PC-3 cells. On the other hand, this peptide exhibited strong cytolytic activity toward PSMA-positive LNCaP cells in a concentration-dependent manner. The carboxypeptidase inhibitor 4,4'-phosphonicobis (butane-1,3-dicarboxylic acid) can inhibit this activity. Moreover, this peptide also exhibited cytolytic activity toward PSMA cDNA-transfected PC-3 cells.
In the bacterial type II fatty acid synthase system, beta-ketoacyl-acyl carrier protein (ACP) synthase III (FabH) catalyzes the condensation of acetyl-CoA with malonyl-ACP. We have identified, expressed, and characterized the Streptococcus pneumoniae homologue of Escherichia coli FabH. S. pneumoniae FabH is approximately 41, 39, and 38% identical in amino acid sequence to Bacillus subtilis, E. coli, and Hemophilus influenzae FabH, respectively. The His-Asn-Cys catalytic triad present in other FabH molecules is conserved in S. pneumoniae FabH. The apparent K(m) values for acetyl-CoA and malonyl-ACP were determined to be 40.3 and 18.6 microm, respectively. Purified S. pneumoniae FabH preferentially utilized straight short-chain CoA primers. Similar to E. coli FabH, S. pneumoniae FabH was weakly inhibited by thiolactomycin. In contrast, inhibition of S. pneumoniae FabH by the newly developed compound SB418011 was very potent, with an IC(50) value of 0.016 microm. SB418011 also inhibited E. coli and H. influenzae FabH with IC(50) values of 1.2 and 0.59 microm, respectively. The availability of purified and characterized S. pneumoniae FabH will greatly aid in structural studies of this class of essential bacterial enzymes and facilitate the identification of small molecule inhibitors of type II fatty acid synthase with the potential to be novel and potent antibacterial agents active against pathogenic bacteria.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Although tibial periprosthetic fractures are uncommon, they are likely to be encountered more frequently with the increased use of total knee arthroplasty, and they present a challenging management problem. Here we present our solution to this problem, which provided a safe, effective means of fracture management, while maintaining the prosthesis.
Speakers' prosodic marking of syntactic constituency is often measured in sentence reading tasks that lack realistic situational constraints on speaking. Results from such studies can be criticized because the pragmatic goals of readers differ dramatically from those of speakers in typical conversation. On the other hand, recordings of unscripted speech do not readily yield the carefully controlled contrasts required for many research purposes. Our research employs a cooperative game task, in which two speakers use utterances from a predetermined set to negotiate moves around gameboards. Results from a set of early versus late closure ambiguities suggest that speakers signal this syntactic difference with prosody even when the utterance context fully disambiguates the structure. Phonetic and phonological analyses show reliable prosodic disambiguation in speakers' productions; results of a comprehension task indicate that listeners can successfully use prosodic cues to categorize syntactically ambiguous fragments as portions of early or late closure utterances.
Explore the source record for details and available documents.