Engineering Orthogonal Methyltransferases to Create Alternative Bioalkylation Pathways.

S-adenosyl-l-methionine (SAM)-dependent methyltransferases (MTs) catalyse the methylation of a vast array of small metabolites and biomacromolecules. Recently, rare carboxymethylation pathways have been discovered, including carboxymethyltransferase enzymes that utilise a carboxy-SAM (cxSAM) cofactor generated from SAM by a cxSAM synthase (CmoA). We show how MT enzymes can utilise cxSAM to catalyse carboxymethylation of tetrahydroisoquinoline (THIQ) and catechol substrates.

Structure and Biocatalytic Scope of Coclaurine N-Methyltransferase.

Benzylisoquinoline alkaloids (BIAs) are a structurally diverse family of plant secondary metabolites, which have been exploited to develop analgesics, antibiotics, antitumor agents, and other therapeutic agents. Biosynthesis of BIAs proceeds via a common pathway from tyrosine to (S)-reticulene at which point the pathway diverges. Coclaurine N-methyltransferase (CNMT) is a key enzyme in the pathway to (S)-reticulene, installing the N-methyl substituent that is essential for the bioactivity of many BIAs.

Reproducibility of carotid-femoral pulse wave velocity in end-stage renal disease patients: methodological considerations.

Background: In end-stage renal disease (ESRD) patients, increased arterial stiffness detected by carotid-femoral pulse wave velocity (cf-PWV) is associated with fatal cardiovascular events and all-cause mortality. Since cf-PWV is an operator-dependent technique, poor reproducibility may be a source of bias in the estimation of arterial stiffness.

Objectives: We assessed the week-to-week reproducibility of cf-PWV and radial artery pulse wave analysis in healthy subjects and ESRD patients.

Ramipril versus placebo in kidney transplant patients with proteinuria: a multicentre, double-blind, randomised controlled trial.

Background: Angiotensin-converting enzyme inhibitors have been shown to reduce the risk of end-stage renal disease and death in non-transplant patients with proteinuria. We examined whether ramipril would have a similar beneficial effect on important clinical outcomes in kidney transplant recipients with proteinuria.

Methods: In this double-blind, placebo-controlled, randomised trial, conducted at 14 centres in Canada and New Zealand, we enrolled adult renal transplant recipients at least 3-months post-transplant with an estimated glomerular filtration rate (GFR) of 20 mL/min/1·73m(2) or greater and proteinuria 0·2 g per day or greater and randomly assigned them to receive either ramipril (5 mg orally twice daily) or placebo for up to 4 years.

Regional Variation in Analytical Techniques used in the Diagnosis and Monitoring of Porphyria: a Case for Harmonisation?

Background: The Royal College of Pathologists of Australasia (RCPA) Porphyrin Quality Assurance Program assesses the measurement of urine, faecal, plasma and whole blood porphyrins and their components plus urinary porphobilinogen and delta aminolaevulinic acid and has laboratories enrolled from around the world. It was observed that there was a wide scatter in results submitted to some subsections of the program.

Methods: A detailed questionnaire covering the analytical techniques used in the diagnosis of porphyria was sent to all laboratories enrolled in the RCPA Porphyrin Quality Assurance Program.

RAN and double-deficit theory.

Lervag and Hulme's neuro-developmental theory and Wolf and Bowers's double-deficit hypothesis were examined in this longitudinal study. A total of 130 children were tested in preschool and followed through fifth grade, when 84 remained in the study. During preschool and kindergarten the participants were given tests of end-sound discrimination (phonological awareness; PA) and the rapid naming of objects (rapid automatic naming; RAN) and were placed into the four groupings of the double-deficit hypothesis.

Male erectile dysfunction following spinal cord injury: a systematic review.

Study Design: Systematic review.

Objective: To review sexuality in persons with spinal cord injuries (SCIs), and to report the effectiveness of erectile interventions.

Methods: Reports from six databases (1966-2003), selected annual proceedings (1997-2002) and manufacturer's information were screened against eligibility criteria.

Fertility following spinal cord injury: a systematic review.

Study Design: Systematic review.

Objectives: To review systematically fertility of persons with spinal cord injuries (SCI) and their partners.

Methods: Reports from six databases (1966-2003), selected annual proceedings (1997-2002) and manufacturer's information were screened against eligibility criteria.

The syntagmatic-paradigmatic shift and reading development.

This study examined developmental change in the word association task as reading acquisition occurred. Syntagmatic responses follow the stimulus world in discourse, 'cold'--'outside', while paradigmatic associates are of the same form class, 'cold'--'hot'. Some 59 children were tested three times during the school year.

Effect of hepatobiliary disease, chronic hepatitis C and hepatitis B virus infections and interferon-alpha on porphyrin profiles in plasma, urine and faeces.

Background: Documentation of the profiles of porphyrins in hepatobiliary disease is limited. Strong associations of hepatitis B and C virus infections with porphyria cutanea tarda have suggested causal relationships. This study aimed to determine the nature of porphyrin abnormalities in hepatobiliary disease and the effect of interferon-alpha on porphyrin profiles.

Staging of primary colorectal carcinomas with fluorine-18 fluorodeoxyglucose whole-body PET: correlation with histopathologic and CT findings.

Purpose: To evaluate the diagnostic usefulness of positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose (FDG) in patients with primary colorectal carcinomas.

Materials And Methods: Forty-eight patients with biopsy-proved (n = 44) or high clinical suspicion for (n = 4) colorectal cancer underwent whole-body PET after intravenous administration of 10 mCi (370 MBq) of FDG. FDG PET results were correlated with computed tomographic (CT), surgical, and histopathologic findings.

Development of oncology protocol using fluorine-18-FDG: one center's experience.

The major types of cancer studied at the authors' facility were colorectal (107 patients), head and neck (122 patients), gastric/esophageal (57 patients), lung (59 patients) and lymphoma (26 patients). This article presents guidelines and techniques for obtaining optimal PET studies. The authors devised these guidelines through trial and error and hope that by sharing them other facilities can avoid unnecessary mistakes and achieve better quality studies more efficiently.

Superiority of SPET to planar imaging in the detection of colorectal carcinomas with 111In monoclonal antibodies.

The aim of this study was to assess the contribution of single photon emission tomography (SPET) to planar imaging of colorectal carcinoma in patients being evaluated with 111In-labelled monoclonal antibodies CYT-103 (OncoScint CR/OV) or IVP ZCE 025. Planar and SPET scans from 110 colorectal carcinoma patients were scored individually as follows: 1=negative, 2=equivocal, 3=positive. The planar and SPET images identified 67 and 93 of 113 documented lesions, respectively.

Fecal coproporphyrin isomers in hereditary coproporphyria.

To see whether the fecal coproporphyrin III:coproporphyrin I (CIII:CI) ratio (determined by HPLC) would be suitable for screening patients at risk of hereditary coproporphyria (HC), we compared such ratios with the lymphocyte coproporphyrinogen oxidase (EC 1.3.3.

The amino acid sequence of the aspartate aminotransferase from baker's yeast (Saccharomyces cerevisiae).

1. The single (cytosolic) aspartate aminotransferase was purified in high yield from baker's yeast (Saccharomyces cerevisiae). 2.