Biomedical subjects

C Yeates

Publications and source records attributed to C Yeates.

9 recordsLinked to original sources

PubMed2006

Construction and analysis of a metagenomic library from an enhanced biological phosphorus removal biomass.

The enhanced biological phosphorus removal (EBPR) process is regularly used for the treatment of wastewater, but suffers from erratic performance. Successful EBPR relies on the growth of bacteria called polyphosphate-accumulating organisms (PAOs), which store phosphorus intracellularly as polyphosphate, thus removing it from wastewater. Metabolic models have been proposed which describe the measured chemical transformations, however genetic evidence is lacking to confirm these hypotheses. The aim of this research was to generate a metagenomic library from biomass enriched in PAOs as determined by phenotypic data and fluorescence in situ hybridisation (FISH) using probes specific for the only described PAO to date, "Candidatus Accumulibacter phosphatis". DNA extraction methods were optimised and two fosmid libraries were constructed which contained 93 million base pairs of metagenomic data. Initial screening of the library for 16S rRNA genes revealed fosmids originating from a range of nonpure-cultured wastewater bacteria. The metagenomic libraries constructed will provide the ability to link phylogenetic and metabolic data for bacteria involved in nutrient removal from wastewater.

Base Sequence↗

PubMed2004

A survey of chronic renal failure in Jamaica.

The prevalence of chronic renal failure (CRF)/end stage renal disease and the accessibility of long term renal replacement therapy in Jamaica were evaluated. The study was conducted at six Jamaican healthcare facilities between July 1998 and December 1999 and included 605 patients with CRF. Men with CRF (57% of patients, mean age of 56.7 years) were significantly older than women (mean age 53.2 years). Hypertension was the most commonly associated medical condition (60.8% of patients) followed by diabetes mellitus (31.4% of patients). The estimated crude point prevalence of CRF in persons 20 years and over at the end of 1999 was 327 per million population. More than one-third of patients with CRF (39%) were receiving renal replacement therapy, the most common modality being haemodialysis, and only 1.8% of patients had received kidney transplantation. The prevalence of chronic renal failure was not increased in areas known to have high soil cadmium levels. Chronic renal failure is a significant public health problem in Jamaica and is placing an increasing financial burden on the healthcare sector.

Adult↗

PubMed2001

Synthesis of N-alkyl substituted indolocarbazoles as potent inhibitors of human cytomegalovirus replication.

The synthesis and antiviral evaluation of unsymmetrical indolocarbazole derivatives of Arcyriaflavin A, substituted with a range of alkyl groups at the indole nitrogen, is described. Structure-activity relationships in this series against human cytomegalovirus (HCMV) replication in cell culture are reported. Compound 4b was identified as potent inhibitor of HCMV (IC(50)=19 nM), which retained activity against a range of HCMV strains including ganciclovir resistant isolates.

Antiviral Agents↗

PubMed2000

Novel forms of ring-hydroxylating dioxygenases are widespread in pristine and contaminated soils.

Ring-hydroxylating dioxygenases (RHDs) are of central importance to bacterial recycling of aromatic hydrocarbons, including anthropogenic pollutants. The database of presently characterized RHDs is biased towards those from organisms readily isolated on anthropogenic substrates. To investigate the extent to which RHDs from extant organisms reflect the natural diversity of these enzymes, we developed a polymerase chain reaction (PCR) method for retrieval of RHD gene fragments from environmental samples. Gene libraries from two contaminated and two pristine soil samples were constructed. None of the inferred peptides from clones examined were identical to previously described RHDs; however, all showed significant sequence homology and contained key catalytic residues. On the basis of sequence identity, the environmental clones clustered into six distinct groups, only one of which included known RHDs. One of the new sequence groupings was particularly widespread, being recovered from all soil samples tested. Comparison of inferred peptide sequences of the environmental clones and known RHDs showed the former to have greater sequence variation at sites thought to influence accessibility of the active site than that seen between currently known RHDs. We conclude that presently characterized RHDs do not adequately represent the diversity of function found in in situ forms.

Amino Acid Sequence↗

PubMed1998

Methods for microbial DNA extraction from soil for PCR amplification.

Amplification of DNA from soil is often inhibited by co-purified contaminants. A rapid, inexpensive, large-scale DNA extraction method involving minimal purification has been developed that is applicable to various soil types (1). DNA is also suitable for PCR amplification using various DNA targets. DNA was extracted from 100g of soil using direct lysis with glass beads and SDS followed by potassium acetate precipitation, polyethylene glycol precipitation, phenol extraction and isopropanol precipitation. This method was compared to other DNA extraction methods with regard to DNA purity and size.

Journal Article↗

PubMed1998

Characterization of a truncated progesterone receptor protein in breast tumors.

The progesterone receptor (PR) mediates the actions of progesterone in the normal and malignant breast. PR is expressed as two proteins, PR B and PR A, which are expressed in normal progesterone target tissues and in breast cancers. A significant proportion of breast cancers contain, in addition, a smaller PR protein of molecular mass 78 kDa (PR78 kDa). The significance of PR78 kDa expression is unknown, and in particular, there are no data on whether PR78 kDa is able to bind ligand and therefore potentially exhibit transcriptional activity. If this smaller PR species exhibits similar differences in function as have been evidenced in vitro for PR A relative to PR B, it is possible that this PR species may be an important component in determination of progesterone response in breast cancer. The purpose of this study was to determine whether the PR78 kDa protein in breast tumors is able to bind ligand and to determine whether posttranscriptional mechanisms contribute to its formation in breast cancers. There was no evidence that PR78 kDa was derived from proteolytic activity of either PR B or PR A. Similarly, although exon-deleted PR transcripts were detected (which could, if translated, give rise to a PR protein similar in size to PR78 kDa), neither the abundance of such transcripts nor their relationship to levels of expressed PR78 kDa protein supported a role for exon deletion in formation of this truncated PR protein. PR78 kDa was not recognized by an antibody specific for PR B, indicating that, like PR A, it lacks the N-terminal portion of PR. PR78 kDa was able to bind the progestin ligand, indicating that it may have transcriptional activity. In summary, this study has shown that a truncated PR protein, found in breast cancers, is ligand-binding and seems to be derived from PR A, indicating that it may have a role in progesterone signaling, although a deeper understanding of its role, if any, in breast cancer remains to be established.

Breast Neoplasms↗

PubMed1997

PCR amplification of crude microbial DNA extracted from soil.

A rapid, inexpensive, large-scale DNA extraction method involving minimal purification has been developed that is applicable to various soil types. DNA was extracted from 100 g of soil using direct lysis with glass beads and sodium dodecyl sulphate (SDS) followed by polyethylene glycol precipitation, potassium acetate precipitation, phenol extraction and isopropanol precipitation. The crude extract could be used in PCR directed at high-copy number (bacterial small subunit rRNA) and single-copy (fungal beta-tubulin) genes.

Base Sequence↗

PubMed1996

Progesterone receptor A and B protein expression in human breast cancer.

The human progesterone receptor (PR) is a ligand-activated nuclear transcription factor which mediates progesterone action in target tissues. Two PR proteins, PR A (81-83 kDa) and PR B (116-120 kDa), have been described and different physiological activities ascribed to each on the basis of in vitro studies, suggesting that their ratio of expression may control progesterone responsiveness in target cells. Presence of PR in breast tumors is an important indicator of likely responsiveness to endocrine agents. However, the relative expression of PR A and B in breast cancer has not been described and its clinical significance has not been addressed. We have examined the expression of PR A and B in PR-positive breast tumors and found that while in most tumors PR A and B were expressed in similar amounts there was a broad overall distribution of PR A:B ratio which deviated significantly from a normal log distribution with tumors containing a PR A:B ration greater than 4 being over-represented in the group. Linear regression analysis revealed that high PR A:B ratios, in general, derived from a low concentration of PR B rather than high expression of PR A. PR A:B protein ratios were not correlated with the age of the patient or with total PR concentration. A third PR protein band (PR 78 kDa) was detected which comprised greater than 20% of total PR protein in a quarter of the tumor samples examined. The characteristics of tumors containing PR 78 kDa were not different from the overall group. In summary, in PR-positive breast tumors the ratio of expression of PR A and B proteins is close to unity as is seen in a number of other progestin target tissues. However, a significant proportion of tumors expressed very low levels of PR B and a consequently high PR A:B ration. Although the clinical consequence of this observation is not known, the in vitro findings that PR A may act as a repressor for PR B suggests that tumors containing primarily PR A may identify a subset of patients with low or aberrant response to endocrine agents.

Adolescent↗

PubMed1995

Characterization of progesterone receptor A and B expression in human breast cancer.

The human progesterone receptor (PR) is a ligand-activated nuclear transcription factor that mediates progesterone action in target tissues. Two PR proteins, PR-A (M(r) 81,000-83,000) and PR-B (M(r) 116,000-120,000), have been described and different physiological activities ascribed to each on the basis of in vitro studies, suggesting that their ratio of expression may control progesterone responsiveness in target cells. Presence of PR in breast tumors is an important indicator of likely responsiveness to endocrine agents. However, the relative expression of PR-A and B in breast cancer has not been described, and its clinical significance has not been addressed. Expression of PR-A and B was measured by immunoblot analysis of 202 PR-positive human breast tumor cytosols. The ratio of expression of the two PR proteins (PR-A/B) ranged from 0.04 to 179.3. The median PR-A/B ratio was 1.26, and 61.4% of samples had PR-A/B ratios between 0 and 2. PR-A/B ratios deviated significantly from a normal log distribution; tumors containing a PR-A/B ratio greater than 4 were overrepresented in the group. Linear regression analysis revealed that high PR-A/B ratios, in general, derived from a low concentration of PR-B rather than high expression of PR-A. PR-A/B protein ratios were not correlated with the age of the patient or with total PR concentration. A third PR protein band (PR78kDa) was detected in a number of samples and comprised greater than 20% of total PR protein in 52 (25.7%) of the 202 tumor samples examined. The range or frequency distribution of PR-A/B ratios in samples containing PR78kDa was not different to the overall group. In summary, in PR-positive breast tumors, the ratio of expression of PR-A and B proteins is close to unity, as is seen in a number of other progestin target tissues. However, a significant proportion of tumors expressed very low levels of PR-B and a consequently high PR-A/B ratio. Although the clinical consequence of this observation is not known, the in vitro findings that PR-A may act as a repressor of PR-B suggest that tumors containing primarily PR-A may identify a subset of patients with low or aberrant response to endocrine agents.

Biopsy↗