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Biomedical subjects

R Bartlett

Publications and source records attributed to R Bartlett.

At least 55 records · Page 3Linked to original sources

Effect of blocking TNF-alpha on intracellular BCG (Bacillus Calmette Guerin) growth in human monocyte-derived macrophages.

Four agents, thalidomide, oxpentifylline, dexamethasone and a polyclonal anti-TNF-alpha antibody, were all shown by specific Elisa to block endogenous TNF-alpha production by Bacillus Calmette Guerin (BCG)-infected human monocyte-derived macrophages in in vitro culture. There was however no significant enhancement of intracellular BCG growth, over a 7-day incubation, in human monocyte-derived macrophages in the presence of any of the TNF-alpha-blocking agents, as determined by both radiometric and CFU counting methods of assessing bacterial viability and growth. The result suggests that the action of TNF-alpha alone is unlikely to be an important effector mechanism in antimycobacterial immunity within human cells.

Antibodies↗

A comparison of the different methods available for determining BCG-macrophage interactions in vitro, including a new method of colony counting in broth.

Different methods of determining BCG viability based on colony forming unit (CFU) counting and radio-isotope labelling were comparatively assessed. These included radio-isotope labelling with [3H]uracil, [3H]uridine, [3H]glycerol, and CFU counting, by both agar plate dilution, and microcolony counting in broth. The sensitivity ranges of the different techniques were determined in both macrophage-free and macrophage-treated systems and used to assess the anti-mycobacterial potential of human monocyte-derived macrophages following BCG infection.

Colony Count, Microbial↗

Involvement of p34cdc2 in establishing the dependency of S phase on mitosis.

Mutants of cdc2+ can disrupt the dependency of S phase on completion of the previous mitosis. By changing the state of p34cdc2 it is possible to reprogramme a cell from entering mitosis to undergoing S phase. This leads to the proposal that the cell cycle can be considered a p34cdc2 cycle, and has implications for the evolution of life cycles.

CDC2 Protein Kinase↗

Yeast as a model system for understanding the control of DNA replication in Eukaryotes.

In the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe, the initiation of DNA replication is controlled at a point called START. At this point, the cellular environment is assessed; only if conditions are appropriate do cells traverse START, thus becoming committed to initiate DNA replication and complete the remainder of the cell cycle. The cdc2+/CDC28+ gene, encoding the protein kinase p34, is a key element in this complex control. The identification of structural and functional homologues of p34 suggests that it has a role in the control of DNA replication in all eukaryotes. The WHI1+, CLN1+ and CLN2+ gene products, identified in S. cerevisiae, are positive regulators that function at START and may interact with p34. Determining how passing the START control point leads to the initiation of DNA replication is a major outstanding challenge in cell cycle studies.

CDC2 Protein Kinase↗

Duration of antagonistic effects of nalmefene and naloxone in opiate-induced sedation for emergency department procedures.

Naloxone is an effective opiate antagonist, but its short half-life limits its usefulness. For outpatient procedures, a longer acting opiate antagonist could eliminate two to four hours of nursing observation in patients postoperatively. A controlled, randomized, double-blind trial comparing the effects of nalmefene, naloxone, and placebo in reversing opiate-induced sedation was carried out to determine efficacy, duration of action, and adverse effects in patients undergoing outpatient procedures. Each patient received 1.5 to 3.0 mg/kg meperidine intravenously before the procedure. After the procedure, each patient received either nalmefene, 1.0 mg; naloxone, 1.0 mg; or saline, 1.0 mL intravenously. Vital signs and assessments for alertness were performed for four hours. Naloxone significantly reversed sedation for only 15 minutes, whereas nalmefene was significantly effective (P less than .05) for up to 210 minutes. Nalmefene was significantly more effective than naloxone in reversing sedation at 60, 90, and 120 minutes. Nalmefene is an effective agent for the reversal of opiate-induced sedation after outpatient procedures.

Adolescent↗

Duchenne muscular dystrophy: detection of deletion carriers by spectrophotometric densitometry.

DNA isolated from a family segregating a deletion in the Duchenne muscular dystrophy gene and control families was digested with restriction enzymes, Southern transferred, and probed with a radioactive dystrophin cDNA probe. The resulting autoradiographs were analyzed with a densitometric spectrophotometer to detect carriers of the deletion. The carrier status of females in the deletion pedigree was independently determined by genomic probes and confirmed by densitometry. In many Duchenne families, deletions will only be observed using cDNA probes which show few restriction fragment length polymorphisms (RFLPs). Such deletions would normally have to be detected using dosage gels. The spectrophotometric densitometry technique used by us does not require dosage gels, and avoids problems arising from non-informative meioses and cross-overs. It should be possible to screen every family with an exon deletion by spectrophotometric densitometry provided the presently available cDNA is suitably reduced to produce fewer bands on autoradiographs.

Autoradiography↗

Segregation of linked probes to myotonic dystrophy in a family demonstrating that 152 and APOC2 are on the same side of DM on 19q.

The two markers most closely linked to the myotonic dystrophy (DM) locus on chromosome 19 are the gene that codes for apolipoprotein CII (APOC2) and the anonymous probe D19S19 (LDR152). Both of these markers show tight linkage to DM, with maximum lod scores of greater than 20 at recombination fractions of less than 0.05. We have identified, in a family in which DM segregates, an affected individual where a meiotic recombination event has occurred in which both of these linked markers have crossed over with the gene defect. This demonstrates that APOC2 and D19S19 are probably on the same side of DM.

Chromosome Mapping↗

Measuring infant metabolism: design and testing of a miniature gas exchange monitor.

A compact closed-circuit gas exchange monitor (GEM) was built for measurement of oxygen consumption (VO2) in ventilated infants. The GEM includes a ventilator-driven slave bellows, a CO2 scrubber, one-way valves to ensure unidirectional flow, and tubing to complete the small-volume low-compliance system, which fits easily between the ventilator (VENT) and the endotracheal tube (ETT). Oxygen consumption is measured by volume loss from a spirometer attached by a one-way valve. Pressure is monitored at the airway, and the VENT is adjusted to attain the desired pressure pattern. The system was leak tested by placing a 3-kg weight on the spirometer bell (continuous positive airway pressure = 20 cm H2O) and then ventilating with peak inspiratory pressures (PIP) of 60 cm H2O without leak. Bench testing for accuracy of volume loss was checked by ventilating the device into another calibrated spirometer and achieving equal volumes. First, four rabbits were studied to determine the range of ventilator backup rates (BUR = 0 to 60), inspiratory times (IT = .2 to .6 seconds), and airway pressures (up to 40/8 cm H2O) attainable by this device. Then six fasted rabbits weighing 2.2 to 4.0 kg were anesthetized with a ketamine-rompun mixture, underwent tracheostomy, and were placed on a pressure VENT. The BUR was set at 20/min and the IT at .5 seconds. The GEM was placed between the VENT and the ETT, and the PIP was adjusted to maintain PaCO2 between 30 and 40 torr, eliminating spontaneous respiration. Oxygen consumption was measured at five-minute intervals for one hour.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Update on the molecular genetics of Duchenne muscular dystrophy.

Three separate lines of evidence led to the assignment of the Duchenne muscular dystrophy (DMD) gene to the 21.2 band on the short arm of the X chromosome. A portion of the putative gene, thought to extend over 1-2 million base pairs has been recently cloned. DNA probes from the Xp21.2 region detect large deletions in 5-20% DMD boys and are presumed to lead to the DMD phenotype in those individuals. Deletions have also been noted in the DNA of patients with Becker muscular dystrophy. These exciting developments have a direct bearing on carrier detection and prenatal diagnosis. Prenatal diagnosis in deletion families approaches greater than 99% accuracy and can be utilized to save 50% of normal male fetuses carried by carrier mothers who would otherwise choose to abort all male fetuses.

Cloning, Molecular↗

Ventricular coupling in constrictive pericarditis.

Because of the close anatomic association, the volume or pressure in one ventricle can directly influence the volume and pressure in the other ventricle. Disease states that reduce pericardial compliance should accentuate this coupling between the ventricles. We examined this hypothesis in six dogs. Constrictive pericarditis was induced by injecting an irritant mixture into the pericardial cavity. Three to 4 weeks after this injection, the hearts were removed and placed in cool cardioplegic solution. Balloons were inserted into each ventricle and the pressure and volume changes caused by increasing the contralateral ventricular volume were measured. Compared with that in a control group of four dogs, the coupling between the ventricles was significantly augmented in the group with constrictive pericarditis. All the measured changes in ventricular pressure or volume caused by increasing contralateral ventricular pressure or volume were significantly greater (p less than .05) in the group with constrictive pericarditis. The results of these experiments show increased coupling between the ventricles with constrictive pericarditis, which helps to explain some of the signs and symptoms of constrictive pericarditis.

Animals↗

A prospective comparison of iotrolan, iohexol and iopamidol for lumbar myelography.

The provisional results are presented of a comparative blind trial of iotrolan, iohexol and iopamidol for lumbar myelography. The aim of the trial was to assess the relative safety, tolerance and radiologic efficacy of the media. From the data available to date the incidence of side effects is similar for all three substances. Iotrolan does not provide specific imaging advantages.

Contrast Media↗