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Biomedical subjects

R Petersen

Publications and source records attributed to R Petersen.

At least 19 recordsLinked to original sources

Double-blind comparison of the clinical, hemodynamic, and electrocardiographic effects of sodium meglumine ioxaglate or iohexol during diagnostic cardiac catheterization.

The clinical effects and the maximal hemodynamic and electrocardiographic effects of two low-osmolality radiographic contrast media (ioxaglate and iohexol) were directly compared during diagnostic cardiac catheterization in a double-blind, randomized study in 80 patients. Because small changes were expected after injection of both of these agents, sensitive ECG and intracardiac-pressure-monitoring methods were used, and maximal changes, as well as mean changes in variables, were analyzed. Symptoms were absent, mild, or moderate in 67-77% of patients after left ventriculography and in 97-100% of patients after coronary arteriography. After left ventriculography, maximum and minimum left ventricular systolic pressure and end-diastolic pressure, the first derivative of left ventricular pressure (dp/dt), heart rate, were significantly altered over the two-minute observation period but were not different from the preinjection values at two minutes after both agents. Small but significant increases in mean aortic pressure, cardiac output, and pulmonary arterial wedge pressures were seen at two minutes after both agents.

Cardiac Catheterization

Cellular transcripts encoded at a locus which permits retrovirus expression in mouse embryonic cells.

Three independent recombinant retroviruses have been activated on insertion into the F2 locus of mouse F9 embryonal carcinoma cells. Each provirus has integrated downstream from the cellular F2 promoter, which is active in transient transfection assays using a chloramphenicol acetyltransferase reporter enzyme. The F2 promoter drives expression of a series of related transcripts in F9 and 3T3 cells, and a single 450-nt transcript in mouse tissues. F2 homologous sequences have been detected in the genomes of all mammalian species tested, and the 450-nucleotide (nt) F2 transcript is expressed in rat and human cells. Three pairs of differently sized F2 cDNA clones have been isolated and analyzed. The largest clones possess two 199-nt 98.5% identical repeats, one of which is present in the smaller clones, as well as the major 450-nt transcript. Activated proviral integration sites map to introns of the largest F2 cDNA clone. While none of the F2 cDNA contains a long open reading frame or homology to databank sequences, evidence suggests that the F2 locus encodes a constitutive function required at high levels, or represents an expressed but nonfunctional, single-copy element, conserved among mammals.

Animals

Irritative symptoms and exposure to mineral wool.

In a cross-sectional study undertaken in 1981 using a postal questionnaire, the prevalence of irritative symptoms was investigated among 2,654 Danish construction workers working with mineral wool. An evaluation was undertaken in a multivariate logit analysis of the relationship between exposure level (measured by hours of exposure to mineral wool per month) and prevalence of symptoms. The analysis controlled for the confounders of age, smoking habits, and exposure to organic solvents. With greater exposure to mineral wool, there was a statistically significant increase in the frequency of irritative symptoms from the eyes, the skin, and the upper respiratory tract. Among construction workers working with mineral wool 160-180 hours per month, two-thirds had these symptoms once a week or oftener. The occurrence was 2-3 times higher compared with the construction workers not working with mineral wool. The relationship between exposure to mineral wool and skin and mucous membrane symptoms may be explained by the irritative action of the fibers that are given off during insulation work.

Adolescent

A stem cell-specific silencer in the primer-binding site of a retrovirus.

Retrovirus expression in embryonal carcinoma (EC) cells is blocked at a postintegration stage of the viral life cycle, in part because of the inadequate function of the viral long terminal repeat promoter in this cell type. However, selection for retrovirus expression in EC cells has identified mutations in Moloney murine leukemia virus (M-MuLV) located in the tRNA primer-binding site (PBS) region which relieve the EC cell-specific repression. We have found that exchanging the M-MuLV proline PBS for a glutamine one in a recombinant virus permits expression in EC cells. By using the recombinant virus as a backbone, the EC cell-specific repressor-binding site (RBS) element has been mapped to M-MuLV nucleotides 147 to 174. The RBS does not require precise positioning downstream of the M-MuLV promoter and can function in either orientation and in an intron, indicating that the regulatory effect is probably at the DNA, rather than RNA, level. We also show that the RBS element can repress heterologous promoters from an upstream position. Our results indicate that the RBS acts as a silencer that its inhibitory effect is mediated by a trans-acting factor, and that the mechanism of action is probably at the level of transcription. Through in vitro binding assays we have identified a binding factor which specifically recognizes the wild-type RBS sequence (binding factor A). The binding characteristics of factor A suggest that it is a stem cell repressor which acts at the M-MuLV RBS. Our DNA-binding assays also have identified a unique binding factor (binding factor Hp) which specifically recognizes a hemimethylated form of the wild-type RBS. This factor may play a role in methylation mediated control of retrovirus expression in EC cells.

Animals

[The treatment of insertion desmopathy in the metatarsus of horses].

Metacarpal or metatarsal exostoses were diagnosed in 112 horses used for sport purposes between January 1976 to December 1987. Fourteen of these patients were treated surgically by subperiosteal removal of the exostosis. All animals which could be followed up had returned to their original use. The average time of use after discharge from the clinic was 38.4 months. Surgery was successful in completely removing the exostoses in 58.3% of these horses. The indications for anaesthesia and resection of the ulnar nerve are discussed.

Animals

Day to day reproducibility of electrically inducible ventricular arrhythmias in survivors of acute myocardial infarction.

Day to day reproducibility of the response to programmed ventricular stimulation has not been evaluated in survivors of acute myocardial infarction. Programmed ventricular stimulation was performed prospectively on 2 consecutive days in 56 patients on an average of 12 +/- 5 days (range 7 to 29) after an acute myocardial infarction. No patient had a history of documented or suspected sustained ventricular tachycardia or fibrillation occurring greater than 48 h after infarction. During initial programmed ventricular stimulation, 21 patients had induction of sustained ventricular tachycardia or fibrillation (Group I), and 35 patients had induction of either nonsustained ventricular tachycardia or no ventricular tachycardia (Group II). Repeat programmed ventricular stimulation in Group I patients induced sustained ventricular tachycardia or fibrillation in 16 of 21 patients (reproducibility 76%); the maximal induced response in the other 5 patients was nonsustained ventricular tachycardia in 2 patients and fewer than six repetitive ventricular responses in 3 patients. The day to day reproducibility was significantly higher for inducible sustained ventricular tachycardia of cycle length greater than or equal to 240 ms compared with rapid sustained ventricular tachycardia of cycle length less than 240 ms (100% versus 44%, p less than 0.009) or ventricular fibrillation (100% versus 43%, p less than 0.009). Repeat programmed ventricular stimulation in Group II patients did not induce sustained ventricular arrhythmias in 31 of 35 patients (reproducibility 89%). Thus, in survivors of acute myocardial infarction, inducible slow sustained ventricular tachycardia was a highly reproducible finding, whereas inducibility of rapid sustained ventricular tachycardia and ventricular fibrillation showed a significant day to day variability.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Prospective evaluation of parenteral magnesium sulfate in the treatment of patients with reentrant AV supraventricular tachycardia.

This study prospectively assessed the electrophysiologic effects of parenteral magnesium sulfate administration on paroxysmal atrioventricular (AV) reentrant supraventricular tachycardia and the efficacy of magnesium to terminate these arrhythmias. Eleven normomagnesemic patients, seven with orthodromic reentrant supraventricular tachycardia that used an accessory AV pathway, and four with typical AV nodal reentry were examined. All patients had a history of sustained supraventricular tachycardia requiring pharmacologic therapy or electrical cardioversion for termination of tachycardia. After baseline electrophysiologic study, including documentation of sustained supraventricular tachycardia that was reproducibly induced, parenteral magnesium sulfate (a bolus of 0.3 mEq/kg of elemental magnesium infused over a 10-minute period followed by a maintenance infusion of 0.2 mEq/kg/hr) was administered during sustained supraventricular tachycardia. The serum magnesium concentration increased from (mean +/- standard deviation) 1.9 +/- 0.2 mg/dl to 4.0 +/- 0.6 mg/dl (p = 0.0001). Except for flushing and mild diaphoresis during infusion of the magnesium sulfate bolus, and dry heaves in one patient, there were no untoward effects or significant changes in systolic blood pressure. During administration of magnesium, the tachycardia cycle length increased from 319 +/- 39 msec to 348 +/- 43 msec (p = 0.0001). Slowing of the tachycardia occurred predominantly in the antegrade limb of the circuit at the level of the AV node with the AH interval increasing from 171 +/- 66 msec to 197 +/- 68 msec (p = 0.0001), whereas there was no significant change in the HV interval (43 +/- 3 msec to 43 +/- 4 msec, p = NS) or the VA interval (106 +/- 43 msec to 110 +/- 47 msec, p = NS) during tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Effect of acute hemodynamic decompensation on electrical inducibility of ventricular arrhythmias in patients with dilated cardiomyopathy and complex nonsustained ventricular arrhythmias.

In patients with dilated cardiomyopathy, hemodynamic decompensation has been postulated to increase vulnerability to reentrant ventricular arrhythmias. To test this hypothesis, we performed programmed ventricular stimulation with three extrastimuli on nine patients with dilated cardiomyopathy and asymptomatic complex ventricular arrhythmias during a period of acute hemodynamic decompensation; programmed ventricular stimulation was then repeated following hemodynamic improvement with nitroprusside. These patients did not have a history of documented or suspected sustained ventricular tachycardia or fibrillation. The mean left ventricular ejection fraction was 0.21 +/- 0.04 (range 0.15 to 0.26). In the baseline state, mean right atrial pressure was 8 +/- 4 mm Hg, pulmonary artery wedge pressure was 20 +/- 3 mm Hg, and cardiac index was 3.2 +/- 0.5 L/min/m2. Following acute hemodynamic decompensation, mean right atrial pressure increased to 16 +/- 5 mm Hg and pulmonary artery wedge pressure to 33 +/- 8 mm Hg; cardiac index decreased to 2.1 +/- 0.5 L/min/m2. In this decompensated state, programmed ventricular stimulation failed to induce sustained or nonsustained ventricular arrhythmias in any patient. Following nitroprusside administration (mean dose 1.5 +/- 1.1 micrograms/kg/min), there were significant decreases in mean right atrial pressure (11 +/- 3 mm Hg) and pulmonary artery wedge pressure (16 +/- 3 mm Hg), and a significant increase in cardiac index (3.1 +/- 1.1 L/min/m2) (p less than 0.05 for all values versus the decompensated state). In the improved hemodynamic state, programmed ventricular stimulation induced nonsustained ventricular tachycardia (six beats) in only one patient, and sustained arrhythmias in none.(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias, Cardiac

Selective translation and degradation of heat-shock messenger RNAs in Drosophila.

The rapid and dramatic induction of heat-shock proteins is accomplished by regulatory mechanisms acting at many different levels. Here we review current knowledge of two cytoplasmic mechanisms employed during the response in the fruit fly Drosophila melanogaster. (1) Heat-shock messages are translated with high efficiency during heat shock while most normal cellular messages are inactive. Sequences in the 5'-untranslated leader of heat shock mRNAs govern their preferential translation. (2) The messages for heat-shock proteins are unstable at normal temperatures. During heat shock, however, they are very stable and accumulate in large numbers. Sequences in their 3'-untranslated regions play a major role in determining their stability.

Animals

Terms of confinement.

Through habit we have chosen words to describe antepartum, intrapartum, and postpartum events that are domineering and restricting and that are consistent with imprisonment. We must be cognizant of the potential impact of our language.

Obstetrics

Oncogenic point mutations in the human retinoblastoma gene: their application to genetic counseling.

Mutations of the retinoblastoma gene, most of which cannot be detected by conventional Southern blotting, are known to cause both the nonhereditary and hereditary forms of retinoblastoma and have been implicated in the development of other cancers. Nonhereditary retinoblastoma is caused by a somatic mutation. Hereditary retinoblastoma is caused by a germ-cell mutation, most often a new one, and thus there is usually no family history of the disease. Unlike patients with the nonhereditary disease, those with the hereditary form are at risk for additional retinoblastomas, and their progeny are at risk for the tumors. We used a sensitive technique of primer-directed enzymatic amplification, followed by DNA sequence analysis, to identify mutations as small as a single nucleotide change in tumors from seven patients with simplex retinoblastoma (with no family history of the disease). In four patients the mutation involved only the tumor cells, and in three it involved normal somatic cells as well as tumor cells but was not found in either parent; thus, these mutations appeared to be new, germ-cell mutations. In addition, we found point mutations in cells from a bladder carcinoma, a small-cell carcinoma of the lung, and another retinoblastoma. We conclude that the technique that we have described can distinguish hereditary from nonhereditary retinoblastoma and that it is useful in risk estimation and genetic counseling.

Base Sequence

Human ribosomal DNA: novel sequence organization in a 4.5-kb region upstream from the promoter.

We have investigated the molecular organization of a portion of the human ribosomal nontranscribed spacer, by determining the sequence of 4580 bp of DNA upstream from the promoter. This region contains two pairs of oppositely oriented Alu elements, each of which is separated by dA (or dT)-rich stretches. One dT-rich region extends over 800 bp and is of variable length in different ribosomal genes. This and other portions of the spacer consist of simple sequences reiterated many times: for instance, (TACAA)26, (TTTC)117, and (TTGC)47. We are able to position the distal junction of the ribosomal repeat and sequences that have the propensity to form alternate structures, such as Z-DNA and bent DNA. A complex DNA methylation pattern and the influence on transcription of analogous regions in other species, suggest that this upstream area may be important to the expression of the human gene.

Base Composition

Parental origin of mutations of the retinoblastoma gene.

Retinoblastoma and osteosarcoma arise from cells that have lost both functional copies of the retinoblastoma gene. Using the cloned retinoblastoma gene and other linked polymorphic loci, it is possible to reconstruct the sequential loss of the two homologous gene copies that precedes the development of these tumours. In non-hereditary tumours, the loss of each of the two homologues occurs somatically; in hereditary cases, the initial mutation is in the germline. Recently, Toguchida et al. reported that the paternally derived copy is preferentially the first one to become mutant during the genesis of non-hereditary osteosarcomas. We report here a similar analysis of patients with retinoblastoma in which we find no such predilection for initial somatic mutations. In contrast, when an initial mutation was a new germline mutation, it was derived from the father, a result which is consistent with new germline mutations arising primarily during spermatogenesis.

Adult

Effects of terbutaline sulfate on fetal cardiac function.

An isolated heart preparation was used to study the effects of terbutaline sulfate (Brethine) on fetal cardiac function. Pregnant guinea pigs received daily subcutaneous injections of terbutaline for 10 day, whereas a control group received placebo injections. Fetal guinea pig hearts were evaluated for cariodynamic and pathologic differences. Fetuses exposed to terbutaline demonstrated a higher mean heart rate (p less than 0.01), a higher mean heart weight (p less than 0.05), a higher mean heart weight/body weight ratio (p less than 0.01), and a trend toward higher left ventricular systolic pressure levels (p less than 0.1). These hemodynamic responses in fetuses exposed to terbutaline may result in increased functional demands that may predispose myocardial tissue to damage.

Animals

Independent insertion of Alu elements in the human ribosomal spacer and their concerted evolution.

A 2,700-bp segment of human ribosomal DNA (rDNA) spacer upstream of the rRNA promoter contains a set of four Alu elements, two in the direction of rRNA transcription and two in the opposite orientation. We report and compare the sequences of these Alu elements found in three rDNA clones and seek to determine the origin of the cluster, either from a single insertion followed by duplications or from multiple simultaneous or independent insertions. The high (20%-27%) divergence among members of a set and the lack of similarity/complementarity of sequences flanking different members of the set demonstrate the independent insertion of each of the four Alu elements into A-rich sequences on the appropriate strand of the rDNA. We also demonstrate that the Alu sets found in different rDNA repeats are subject to concerted evolution, yielding divergences of only 0.4%-3% between Alu elements in equivalent positions. However, the pairs of adjacent similarly oriented Alu elements do not show reduced divergence, indicating that there is no recombination or gene conversion between similarly oriented but not equivalently positioned Alu elements. Finally, crossing-over must occur in the rDNA junction region between Alu element 3 and the nonribosomal sequences at the telomere end of the acrocentric chromosome, so that the Alu elements of the terminal rDNA repeats and the terminal repeats themselves evolve in concert with the rDNA repeats located internally in the tandem array.

Base Sequence

Plane crash.

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Aircraft