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Biomedical subjects

S French

Publications and source records attributed to S French.

At least 19 recordsLinked to original sources

Consequences of replication fork movement through transcription units in vivo.

To examine the basis for the evolutionary selection for codirectionality of replication and transcription in Escherichia coli, electron microscopy was used to visualize replication from an inducible ColE1 replication origin inserted into the Escherichia coli chromosome upstream (5') or downstream (3') of rrnB, a ribosomal RNA operon. Active rrnB operons were replicated either in the same direction in which they were transcribed or in the opposite direction. In either direction, RNA polymerases were dislodged during replication. When replication and transcription were codirectional, the rate of replication fork movement was similar to that observed in nontranscribed regions. When replication and transcription occurred in opposite directions, replication fork movement was reduced.

DNA Replication

Phase II trial of fludarabine phosphate for adenocarcinoma of the pancreas. An Illinois Cancer Center study.

We have conducted a phase II trial of fludarabine phosphate for advanced measurable adenocarcinoma of the pancreas. The drug was administered every 4 weeks by a daily-times-5 bolus schedule beginning at 20 mg/m2/day. No responses were observed in 20 evaluable patients, 18 of whom were previously untreated. Dose-limiting toxicity was leukopenia, and gastroenterologic side effects were frequent. Life-threatening or fatal renal dysfunction occurred in 3 patients. In this schedule fludarabine phosphate is ineffective against adenocarcinoma of the pancreas and appears to have unpredictable severe renal toxicity.

Adenocarcinoma

Definition of an advanced nursing practice role in the NICU: the clinical nurse specialist/neonatal practitioner.

We surveyed 655 health professionals affiliated with tertiary level neonatal intensive care units in Canada and the United States to define an expanded role for nurses in neonatology and to determine the educational requirements for the role. The role, comprising advanced clinical practice, educational, research, and administrative responsibilities, is a blend of nurse practitioner and clinical nurse specialist activities. Based on survey findings, a neonatal stream within the existing Master of Health Sciences program at McMaster University was developed. To date, 15 clinical nurse specialists/neonatal practitioners (CNS/NPs) are employed in five neonatal intensive care units in Ontario and other related institutions. A randomized trial to evaluate these individuals is in progress.

Humans

Conventional and right precordial ECGs, creatine kinase, and radionuclide angiography in post-traumatic ventricular dysfunction.

Right ventricular infarction due to ischemic heart disease can be diagnosed by a right precordial electrogram or by first-pass radionuclide angiography (FPRNA). Prior FPRNA studies have shown that cardiac dysfunction after blunt chest trauma (myocardial contusion) is most often due to right ventricular dysfunction. We hypothesized that right ventricular dysfunction due to ischemic heart disease and myocardial contusion should produce similar ECG changes due to myocyte disruption. The purpose of our study was to evaluate the diagnostic value of the right precordial electrogram in suspected cardiac contusion. Thirty-five patients with suspected myocardial contusion based on mechanism of injury/clinical findings and no history of clinical heart disease were enrolled prospectively. All patients had conventional ECG, right precordial electrogram, and FPRNA studies. Twenty patients had normal cardiac scans (group 1); percentage of myocardial creatine kinase (CK-MB) was measured in 12 of these patients and was less than 5% in 11. Fifteen patients had abnormal cardiac scans (wall motion abnormality and/or decreased right ventricular ejection fraction) (mean, 34% +/- 7% [SD]; normal, greater than 40%) (group 2); percentage of CK-MB was measured in 13 of 15 patients and was less than 5% in all 13. Conventional ECGs and right precordial electrograms in all patients were analyzed for differences in heart rate, PR interval, QRS duration, corrected QT interval, and the axis of the frontal and horizontal plane QRS complex and ST segment. There were no significant differences between group 1 and group 2 patients. No patient with myocardial contusion diagnosed by FPRNA had elevated ST segments in V4R through V6R or a percentage CK-MB of more than 5%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

The role of ductal obstruction on the course of hemorrhagic pancreatitis in the pig.

The effect of relieving pancreatic duct obstruction after the onset of hemorrhagic pancreatitis was investigated. Hemorrhagic pancreatitis was produced in 20 pigs by a bile salt-trypsin retrograde injection technique. In half the pigs the pancreatic duct was permanently ligated, and in the other half the ductal obstruction was relieved 2 h after the onset of hemorrhagic pancreatitis. The overall mortality rate was the same in both groups by 24 h. No difference was found between the groups in the gross and microscopic appearance of histological samples taken from the pancreas immediately after death. The biochemical parameters measured to assess the severity of pancreatitis such as calcium, BUN, creatinine, glucose, proteins, and hematocrit did not show any difference between the two groups. The serum amylase level, a measure of ductal obstruction, was less at 24 h and even lower at 48 h in the release group as compared to the non-release group. This difference suggests that the ductal obstruction was relieved, as the amylase levels declined at 24 and 48 h. Hemodynamic variables, including cardiac output, pulmonary artery pressure, pulmonary wedge pressure, central venous pressure, and aortic pressure were followed. No significant difference was found in any of these parameters between the two groups. The absence of any significant differences in hemodynamic status, histopathological findings, and biochemical analysis in our pigs, if translatable to man, does not lend support to early operative intervention in gallstone pancreatitis in the hope that those patients who already have hemorrhagic pancreatitis will benefit from early pancreatic ductal decompression.

Animals

Electron microscopic visualization of trp operon expression in Salmonella typhimurium.

Transcriptional activity of plasmids carrying wild-type and mutant trp operons was visualized in cell lysates of Salmonella typhimurium. Plasmid and transcription-unit sizes varied with the size of the cloned operon. Following 3-(3-indolyl)acrylic acid derepression, all operons of a particular type exhibited the same high level of transcriptional activity. An estimated 11-14 transcripts must be initiated each minute to maintain the 190-base-pair spacing of RNA polymerases observed on the promoter-proximal half of the wild-type trp operon. A decline in RNA polymerase density was observed on promoter-distal portions of cloned trp operons, which may be attributable to premature transcription termination accompanying translation inhibition due to indolylacrylic acid's interference with normal tryptophanyl-tRNA synthetase activity.

Chromosome Deletion

Modulation of in vitro cellular immune response by histamine agonists or antagonists in murine species.

The generation of secondary cytotoxic T-lymphocyte (CTL) responses in vitro toward allogeneic P815 mastocytoma cells were suppressed 60-80% when 10(-4) mol/l histamine, 10(-5) mol/l dimaprit (S-[3-(N,N-dimethylamino) propyl]isothiourea dihydrochloride) or 10(-5) mol/l impromidine were present in the culture. Three lines of evidence suggest this observation was a result of an active suppression mechanism and not a result of drug toxicity: Control level activity was obtained when Interleukin-2/T-cell growth factor (IL-2) containing supernatants were added to suppressed cultures. Removal of drug after incubation resulted in control level responses upon reculture. The addition of these H2 agonists to spleen cells from nonimmune animals did not affect the primary CTL response to P815. The effects of H1 and H2 antagonists were also tested in this model. The observed suppression was abrogated by the H2 antagonists cimetidine and mifentidine but not by the H2 antagonist ranitidine nor H1 antagonists, chlorpheniramine, pyrilamine or diphenhydramine. These results suggest regulation of CTL differentiation to alloantigens can be modulated by H2 reactive entities.

Animals

Researching disability: the way forward.

This paper critically examines the individualistic and medicalized assumptions underlying much research on disability. The OPCS surveys of disability, in particular, are examined. Based on the perceptions of disabled people and their organizations, and drawing on a series of seminars on disability research which took place in 1991, an alternative social view of disability is presented and applied to research. It is concluded that the assumptions underlying much disability research, especially when they are translated into practice, are oppressive to disabled people, and that participatory and emancipatory research needs to be developed in order to assist disabled people in their struggle for empowerment.

Persons with Disabilities