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Biomedical subjects

J Chambers

Publications and source records attributed to J Chambers.

At least 55 records · Page 3Linked to original sources
PubMed1999

Identification, molecular cloning, expression, and characterization of a cysteinyl leukotriene receptor.

The cysteinyl leukotrienes (CysLTs) have been implicated in the pathophysiology of inflammatory disorders, in particular asthma, for which the CysLT receptor antagonists pranlukast, zafirlukast, and montelukast, have been introduced recently as novel therapeutics. Here we report on the molecular cloning, expression, localization, and pharmacological characterization of a CysLT receptor (CysLTR), which was identified by ligand fishing of orphan seven-transmembrane-spanning, G protein-coupled receptors. This receptor, expressed in human embryonic kidney (HEK)-293 cells responded selectively to the individual CysLTs, LTC(4), LTD(4), or LTE(4), with a calcium mobilization response; the rank order potency was LTD(4) (EC(50) = 2.5 nM) > LTC(4) (EC(50) = 24 nM) > LTE(4) (EC(50) = 240 nM). Evidence was provided that LTE(4) is a partial agonist at this receptor. [(3)H]LTD(4) binding and LTD(4)-induced calcium mobilization in HEK-293 cells expressing the CysLT receptor were potently inhibited by the structurally distinct CysLTR antagonists pranlukast, montelukast, zafirlukast, and pobilukast; the rank order potency was pranlukast = zafirlukast > montelukast > pobilukast. LTD(4)-induced calcium mobilization in HEK-293 cells expressing the CysLT receptor was not affected by pertussis toxin, and the signal appears to be the result of the release from intracellular stores. Localization studies indicate the expression of this receptor in several tissues, including human lung, human bronchus, and human peripheral blood leukocytes. The discovery of this receptor, which has characteristics of the purported CysLT(1) receptor subtype, should assist in the elucidation of the pathophysiological roles of the CysLTs and in the identification of additional receptor subtypes.

Amino Acid Sequence↗
PubMed1999

DNA microarrays of the complex human cytomegalovirus genome: profiling kinetic class with drug sensitivity of viral gene expression.

We describe, for the first time, the generation of a viral DNA chip for simultaneous expression measurements of nearly all known open reading frames (ORFs) in the largest member of the herpesvirus family, human cytomegalovirus (HCMV). In this study, an HCMV chip was fabricated and used to characterize the temporal class of viral gene expression. The viral chip is composed of microarrays of viral DNA prepared by robotic deposition of oligonucleotides on glass for ORFs in the HCMV genome. Viral gene expression was monitored by hybridization to the oligonucleotide microarrays with fluorescently labelled cDNAs prepared from mock-infected or infected human foreskin fibroblast cells. By using cycloheximide and ganciclovir to block de novo viral protein synthesis and viral DNA replication, respectively, the kinetic classes of array elements were classified. The expression profiles of known ORFs and many previously uncharacterized ORFs provided a temporal map of immediate-early (alpha), early (beta), early-late (gamma1), and late (gamma2) genes in the entire genome of HCMV. Sequence compositional analysis of the 5' noncoding DNA sequences of the temporal classes, performed by using algorithms that automatically search for defined and recurring motifs in unaligned sequences, indicated the presence of potential regulatory motifs for beta, gamma1, and gamma2 genes. In summary, these fabricated microarrays of viral DNA allow rapid and parallel analysis of gene expression at the whole viral genome level. The viral chip approach coupled with global biochemical and genetic strategies should greatly speed the functional analysis of established as well as newly discovered large viral genomes.

Base Sequence↗
PubMed1999

The relation between transaortic pressure difference and flow during dobutamine stress echocardiography in patients with aortic stenosis.

OBJECTIVE: To investigate the relation between transaortic pressure difference and flow in patients with aortic stenosis. METHODS: 50 asymptomatic patients with all grades of aortic stenosis were studied using dobutamine stress echocardiography. Individual plots of mean pressure drop against flow were drawn. Comparisons were made between grades of aortic stenosis as defined by the continuity equation. RESULTS: A significant linear relation between pressure difference and flow was found in 34 patients (68%). There was a significant curvilinear relation in four (8%), while no significant regression line could be fitted in 12 (24%). In the 34 patients with linear fits, the slopes (mean (SD)) were 0.08 (0.07) in mild, 0.10 (0.04) in moderate, and 0.22 (0.16) in severe aortic stenosis (p = 0. 0055). CONCLUSIONS: Transaortic pressure difference can be related directly to flow in many patients with all grades of aortic stenosis. However, there are individual differences in slope and intercept suggesting that resistance calculated at rest may not always be representative. Raw pressure drop/flow plots may be an alternative method of describing valve function.

Adult↗
PubMed1998

Effect of omeprazole in patients with chest pain and normal coronary anatomy: initial experience.

Gastroesophageal reflux is frequently found in patients with chest pain despite normal coronary anatomy, but little data on the effect of specific medication exist. After performing 24 h ambulatory pH monitoring and the Bernstein test on 23 patients with normal coronary anatomy, we gave omeprazole, 40 mg nocte, for six weeks to these and to a control group of ten patients with coronary disease. Pain episodes per fortnight fell from 16.2 to 12.0 (P=0.02) in the patients with normal anatomy and from 19.6 to 17.1 (nonsignificant) in the patients with coronary disease. Improvement occurred in seven (30%) of the patients with normal coronary anatomy compared with one (10%) of those with coronary disease, while complete resolution occurred in four (17%) and none, respectively. Improvement or complete resolution were not predicted by the results of 24 h pH monitoring, although there was a trend towards the prediction of efficacy by the Bernstein test. Omeprazole shows promise as a treatment for patients with chest pain despite normal coronary anatomy and larger placebo-controlled trials should now be undertaken.

Adult↗
PubMed1998

Is it safe to cardiovert atrial fibrillation without anticoagulation if the transoesophageal echocardiogram is normal?

The risk of thromboembolism after unprotected DC cardioversion for chronic atrial fibrillation is 5%. The use of transoesophageal echocardiographic guidance probably reduces this risk to around 1.3%. However, after conventional courses of anticoagulation, the risk is only 0.3 to 0.8%. Until there is further information from large randomised trials, the routine use of transoesophageal echocardiography cannot be recommended. However it should be considered in acute onset atrial fibrillation of less than 2 days duration in the presence of underlying structural heart disease or in individual patients who have previously suffered an embolic event.

Anticoagulants↗