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Biomedical subjects

R P Martin

Publications and source records attributed to R P Martin.

At least 19 recordsLinked to original sources

5 S rRNA and tRNA import into human mitochondria. Comparison of in vitro requirements.

In vivo, human mitochondria import 5 S rRNA and do not import tRNAs from the cytoplasm. We demonstrated previously that isolated human mitochondria are able to internalize a yeast tRNA(Lys) in the presence of yeast soluble factors. Here, we describe an assay for specific uptake of 5 S rRNA by isolated human mitochondria and compare its requirements with the artificial tRNA import. The efficiency of 5 S rRNA uptake by isolated mitochondria was comparable with that found in vivo. The import was shown to depend on ATP and the transmembrane electrochemical potential and was directed by soluble proteins. Blocking the pre-protein import channel inhibited internalization of both 5 S rRNA and tRNA, which suggests this apparatus be involved in RNA uptake by the mitochondria. We show that human mitochondria can also selectively internalize several in vitro synthesized versions of yeast tRNA(Lys) as well as a transcript of the human mitochondrial tRNA(Lys). Either yeast or human soluble proteins can direct this import, suggesting that human cells possess all factors needed for such an artificial translocation. On the other hand, the efficiency of import directed by yeast or human protein factors varies significantly, depending on the tRNA version. Similarly to the yeast system, tRNA(Lys) import into human mitochondria depended on aminoacylation and on the precursor of the mitochondrial lysyl-tRNA synthetase. 5 S rRNA import was also dependent upon soluble protein(s), which were distinct from the factors providing tRNA internalization.

Amino Acid Sequence↗

RNA delivery into mitochondria.

Mitochondria, though containing their own genome, import the vast majority of their macromolecular components from the cytoplasm. If the mechanisms of pre-protein import are well understood, the import of nuclear-coded RNAs into mitochondria was investigated to a much lesser extent. This targeting, if not universal, is widely spread among species. The origin and the mechanisms of RNA import seem to differ from one system to another and striking differences are observed even in closely related species. We describe data concerning the various experimental systems of studying RNA import with emphasis on the model of the yeast Saccharomyces cerevisiae, which was studied in our laboratory. We compare various requirements of RNA import into mitochondria in different species and demonstrate that this pathway can be transferred from yeast to human cells, in which tRNAs normally are not imported. We speculate on the possibility to use RNA import for biomedical purposes.

Animals↗

The repeatability of echocardiographic determination of right ventricular output in the newborn.

BACKGROUND: Non-invasive measurement of left ventricular output has been shown to be a repeatable technique. Little is known about the repeatability using echocardiography in determining pulmonary arterial diameters or right ventricular output. AIMS: To find the most repeatable point at which to measure pulmonary arterial diameter, and to compare the repeatability of determining right ventricular output with left ventricular output. METHODS: We assessed the Intra-observer and inter-observer repeatability for measuring the diameter of the pulmonary trunk in 24 term and 26 preterm infants, respectively. Interobserver repeatability was assessed for the diameters of the pulmonary trunk and aorta, for stroke distance, and for left and right ventricular output. RESULTS: The coefficients of variation for intra-observer repeatability were 4%, 7.5% and 9% respectively for measurements of the pulmonary valve, the pulmonary trunk, and the right ventricular outflow tract. There were significant differences between observers for measurement of the pulmonary trunk (p<0.001) and right ventricular outflow tract (p=0.011) but not for the pulmonary valve measured in either its long (p=0.22) or short axis (p=0.22). Significant differences between observers were also found for the pulmonary stroke distance measured in the long axis (p=0.004) and aortic diameter at end-diastole (p<0.001). The other parameters did not differ significantly and were used to calculate right and left ventricular output, respectively. Mean left ventricular output was 241 mls/kg/min, with mean differences between observers of 0.6 mls/kg/min (95% confidence interval (CI): -39.2 to 40.3 mls/kg/min). Mean right ventricular output was 255 mls/kg/min, with mean differences of 0.3 mls/kg/min (95% CI: -24.1 to 23.4 mls/kg/min). CONCLUSION: Measuring the diameter of the pulmonary trunk at the base of the valvar hinge points was most repeatable. Repeatability of right ventricular output was similar to that of left, with absolute values similar to those published by other workers.

Analysis of Variance↗

Transesophageal echo detection of postpartum coronary artery dissection.

A 40-year-old woman, 1 week postpartum, presented with an acute anterior-septal myocardial infarction, caused by an intrawall hematoma (dissection without intimal flap) in her proximal left anterior descending coronary artery-the diagnosis being initially suggested by transesophageal echo. Discussion of this entity follows.

Adult↗

The role of transesophageal echocardiography in the diagnosis and management of patients with aortic perivalvular abscesses.

Aortic valve abscesses (AVAs) are a devastating complication of aortic valve endocarditis. Over 8 years, 25 patients were diagnosed with AVA by transesophageal echo (TEE). Management and outcomes were then analyzed. Eleven (44%) AVAs involved prosthetic valves, and 6 (24%) occurred in congenitally malformed valves. Twenty patients (80%) underwent surgical intervention; the rest were treated medically. Eleven (44%) of the patients died [6 (30%) surgery patients and all the medical patients]. Eight of 11 (73%) patients who died were culture positive for Staphylococcus aureus. All patients with congenitally malformed aortic valves underwent surgical intervention and survived. We conclude that: (1) despite advances in therapy and diagnosis, patients with AVAs have a high mortality rate; (2) prognosis with AVA is especially poor when S aureus is the infectious organism; (3) patients with AVAs in congenitally malformed valves have a great outcome with surgery; (4) patients treated medically have a very poor prognosis; earlier identification by TEE may be critical to improving survival.

Abscess↗

Suppression of mutations in mitochondrial DNA by tRNAs imported from the cytoplasm.

Mitochondrial import of a cytoplasmic transfer RNA (tRNA) in yeast requires the preprotein import machinery and cytosolic factors. We investigated whether the tRNA import pathway can be used to correct respiratory deficiencies due to mutations in the mitochondrial DNA and whether this system can be transferred into human cells. We show that cytoplasmic tRNAs with altered aminoacylation identity can be specifically targeted to the mitochondria and participate in mitochondrial translation. We also show that human mitochondria, which do not normally import tRNAs, are able to internalize yeast tRNA derivatives in vitro and that this import requires an essential yeast import factor.

Acylation↗

The aminoacceptor stem of the yeast tRNA(Lys) contains determinants of mitochondrial import selectivity.

Yeast tRNA(Lys)CUU is nucleus-encoded and is partially imported into the mitochondria. Another lysine isoacceptor, tRNA(Lys)SUU, is also nucleus-encoded but is not imported. These two tRNAs differ in 21 bases. We have previously localised import selectivity determinants in the anticodon arm. By in vitro import of mutant transcripts and by expression of mutant tRNA genes in vivo we show here that the first base pair (1:72) and the discriminator base 73 are also relevant to import selectivity. Replacement of bases 1:72 in tRNA(Lys)SUU by those of tRNA(Lys)CUU makes it importable with a transport efficiency similar to natural.

Anticodon↗

Nausea during pregnancy: relation to early childhood temperament and behavior problems at twelve years.

Associations between maternal nausea during pregnancy and child behavioral outcomes were investigated in a large birth cohort. Generally, 2nd- and 3rd-trimester nausea were more predictive of child outcomes than 1st-trimester nausea. Children whose mothers reported nausea in middle or late pregnancy had lower sensory thresholds and higher levels of activity and emotional intensity in infancy and were reported to be lower in task persistence at age 5. At age 12, these children were viewed by teachers as more careless with their school work and as having more attentional and learning problems.

Age Factors↗

Development of a system to record cardiac output continuously in the newborn.

Intermittent recordings of Doppler flow velocity and cardiac output are of value during intensive care of the sick newborn infant but result in repeated disturbance of the child. We describe a new device for making continuous precordial recordings of Doppler flow velocity from the pulmonary artery in healthy resting newborn infants. Optimal probe siting was evaluated in six babies, and signals were found to be best when the pulmonary artery was insonated from the mid left parasternum. Continuous recordings were made in 13 other babies. Pulmonary artery velocities and, by calculation, cardiac output were measured continuously over periods ranging from 24 to 60 min. Median right ventricular output ranged widely from 148 to 246 mL x kg(-1) x min(-1). In contrast, for individual babies, the values were remarkably stable: the interquartile ranges varied from 13.2 to 29.9 mL x kg(-1) x min(-1). The simultaneous display of signal power allowed independent assessment of artifactual changes in cardiac output. This technique is feasible in healthy term infants and now requires evaluation in the intensive care setting where it may provide useful information concerning trends and short-term variability in right ventricular output.

Cardiac Output↗

Structural requirements of tRNALys for its import into yeast mitochondria.

In the yeast Saccharomyces cerevisiae, one of the two cytoplasmic lysine tRNAs, tRNACUULys, is partially associated with the mitochondrial matrix. Mitochondrial import of this tRNA requires binding to the precursor of the mitochondrial lysyl-tRNA synthetase, pre-MSK, and aminoacylation by the cytoplasmic lysyl-tRNA synthetase, KRS, appears to be a prerequisite for this binding. The second lysine isoacceptor tRNAmnmLys5s2UUU [where 5-[(methylamino)-methyl]-2-thiouridine is mnm5s2U] is exclusively localized in the cytoplasm. To study import determinants within the tRNACUULys molecule, we introduced a panel of replacements in the original sequences of the imported and nonimported lysine tRNAs that correspond to domains or individual residues that differ between these two isoacceptors. The mutant transcripts were tested for import, aminoacylation, and binding to pre-MSK. Import and aminoacylation efficiencies correlate well for the majority of mutant transcripts. However, some poorly aminoacylated transcripts were rather efficiently imported. Surprisingly, these transcripts retained binding capacity to pre-MSK. In fact, all imported transcripts retained pre-MSK binding capacity but nonimported versions did not, suggesting that this binding, rather than aminoacylation, is essential for import. Substitution of the anticodon arm of tRNACUULys with that of tRNAmnmLys5s2UUU abolished import without affecting aminoacylation. A version of tRNAmnmLys5s2UUU with an anticodon CUU was efficiently imported in vitro and was also found to be imported in vivo. This implies that the anticodon arm, especially position 34, is important for recognition by the import machinery. A nicked tRNACUULys transcript is still imported but its import requires reannealing of the two tRNA moieties, which implies that tRNACUULys is imported as a folded molecule.

Anticodon↗

Effects of infant temperament and early intervention on the psychiatric symptoms of adolescents.

OBJECTIVE: To evaluate effects of infant temperament traits and early home-based intervention on psychiatric symptoms in adolescence. METHOD: The sample comprised 100 children born in 1975-1976. The families of 54 children received family counseling during the first 5 years of the child's life (10 times/year); 46 children served as a control group for counseling. At age 6 months the infants' temperament traits were evaluated by the Carey Infant Temperament Questionnaire filled out by the mother. At age 14 to 15 years the psychiatric symptoms of the adolescents were assessed by the Child Behavior Checklist and the Youth Self-Report. RESULTS: A fussy/demanding temperament in infancy was found to predict psychiatric symptoms in adolescence. A family counseling program during infancy protected subjects from developing psychiatric symptoms in adolescence. CONCLUSIONS: It may be possible to improve the psychosocial prognosis of children at temperamental risk by home-based intervention focused on parent-child interaction.

Adolescent↗

Right-sided cardiac tumors detected by transesophageal echocardiography and its usefulness in differentiating the benign from the malignant ones.

Eighteen patients (3 men and 15 women; mean age 63 years) with right-sided tumors were evaluated by both transthoracic and transesophageal echocardiography from 1989 to 1996. The indications for echocardiographic studies included evaluation for a presumed mass and further evaluation of ventricular function and valvular function. Fifteen patients had right atrial tumors. These included 5 hypernephromas, 4 myxomas, 2 angiosarcomas, 1 lipoma, 1 cavernous hemangioma, 1 hepatoma, and 1 chondrosarcoma. Three patients had right ventricular (RV) tumors: 1 metastatic olfactory neuroblastoma, a leiomyosarcoma, a chondrosarcoma, and a fourth patient had infiltration of the RV free wall of unknown etiology. Biopsy of either right atrial or RV masses was performed with transesophageal echocardiographic guidance in 2 patients, and allowed histologic diagnosis before surgical resection. These findings indicate that tumors are more often found in the right atrium than in the right ventricle, and females predominate. Most tumors arising within the right atrium are benign, whereas those extending into the right atrium from outside are malignant. RV tumors are rarely encountered; when present, they are likely to be malignant.

Adult↗

Recanalization of the left atrial appendage demonstrated by transesophageal echocardiography.

Closure of the fibrillating left atrial appendage has been recommended during mitral valve operations to help prevent thrombus formation and systemic embolization postoperatively. We report recanalization of the appendage orifice in 6 patients after surgical closure by pursestring suturing at the time of mitral valve replacement. Transesophageal echocardiography demonstrated disruption of the closure line and partial recanalization of the sutured orifice with relatively high velocity flow between the left atrial body and the appendage.

Diagnosis, Differential↗

Unsatisfactory results of a first-generation modular femoral stem implanted without cement. A 4- to 9-year follow-up study.

Eighty primary total hip arthroplasties were performed using a first-generation modular femoral stem inserted without cement. Modular distal sleeves made of methacrylate were used in 33% of the hips. Dorr type B or C femoral geometry was present in 80% of the cases. The mean follow-up period was 81 months with a minimum of 48 months. Satisfactory clinical results were observed in 74% of the hips at the final follow-up visit. Revision of the stem had been performed in 14% of the hips, all for aseptic loosening. The overall mechanical failure rate was 48%. Canal fill by the stem was not any better with the sleeves than without. The incidence of failure, however, was less in those hips in which sleeves were used. Femoral osteolysis was present in 19% of the hips. The experience with this particular stem design has been disappointing.

Adult↗

Diagnosis of esophageal varices by transesophageal echocardiography: a mimicker of aortic disease.

The use of transesophageal echocardiography is well established in the emergency department diagnosis of traumatic aortic diseases. It has very high sensitivity and specificity compared with those of other tests. The physician performing transesophageal echocardiography should be aware of conditions that can mimic aortic pathologic conditions, thus leading to an incorrect diagnosis. We report a case in which the presence of previously undiagnosed esophageal varices mimicked traumatic aortic disease.

Aged↗

Ciprofloxacin treatment of bacterial endocarditis involving prosthetic material after cardiac surgery.

Two children with cyanotic congenital heart disease and Gram negative bacterial infection of prosthetic material after cardiac surgery were treated successfully with oral ciprofloxacin, initially in combination with netilmicin. The use of oral ciprofloxacin allowed prolonged outpatient treatment to be given, avoiding the need for intravenous access and early repeat surgery.

Anti-Infective Agents↗