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Biomedical subjects

J D Carroll

Publications and source records attributed to J D Carroll.

At least 37 records · Page 2Linked to original sources

Identification and characterization of uvrA, a DNA repair gene of Deinococcus radiodurans.

Deinococcus radiodurans is extraordinarily resistant to DNA damage, because of its unusually efficient DNA repair processes. The mtcA+ and mtcB+ genes of D. radiodurans, both implicated in excision repair, have been cloned and sequenced, showing that they are a single gene, highly homologous to the uvrA+ genes of other bacteria. The Escherichia coli uvrA+ gene was expressed in mtcA and mtcB strains, and it produced a high degree of complementation of the repair defect in these strains, suggesting that the UvrA protein of D. radiodurans is necessary but not sufficient to produce extreme DNA damage resistance. Upstream of the uvrA+ gene are two large open reading frames, both of which are directionally divergent from the uvrA+ gene. Evidence is presented that the proximal of these open reading frames may be irrB+.

Adenosine Triphosphatases↗

Sequencing, targeted mutagenesis and expression of a recA gene required for the extreme radioresistance of Deinococcus radiodurans.

Deinococcus radiodurans and other members of the same genus share extreme resistance to ionizing radiation and many other agents that damage DNA. A DNA damage-sensitive and natural transformation-deficient strain generated by chemical mutagenesis (strain rec30) was found to be defective in a gene that has extended homology with recA of Escherichia coli. Upon transformation with a chromosomal DNA fragment that contained this deinococcal recA gene from wild-type (wt) D. radiodurans both DNA damage resistance and full transformation competence were restored in the rec30 mutant. Targeted insertional mutagenesis of the deinococcal recA gene was used to construct a mutant isogenic with the wt. The insertional mutant was phenotypically indistinguishable from strain rec30, indicating that the recA defect alone was responsible for observed phenotypic alterations. For example, in the case of ionizing radiation, the D37 of the wt was about 1.75 Mrad, while the D37 of rec30 and the insertional mutant were both 25 krad, a 70-fold decrease. Evidence is presented that expression of the deinococcal recA gene in E. coli is lethal, suggesting that the mode of interaction of the deinococcal RecA protein with nucleic acids or other cellular proteins differs at least in part from RecA of E. coli.

Amino Acid Sequence↗

Peripheral arterial angioplasty balloons as adjuncts to percutaneous coronary revascularization.

Although PTCA balloon technology has improved dramatically since the first catheters were introduced over a decade ago, some limitations remain. The largest conventional balloon size available is 4.0 mm diameter. Larger size balloons are sometimes necessary for saphenous vein graft dilatation or in very large native coronary arteries. Also, adjunctive balloon angioplasty is used frequently after atherectomy and other coronary device therapy. Current generation balloons are not always necessary in this setting, since a large lumen has already been established. Thus, it has become useful in our laboratory to use peripheral arterial angioplasty balloons for both large coronary vessel dilatation, and also for adjunctive dilatation after device use. We describe our initial experience with peripheral arterial angioplasty balloons as adjuncts to percutaneous coronary revascularization.

Aged↗

Effect of atrial septal occlusion on mitral area after Inoue balloon valvotomy.

The purpose of this study was to examine the influence of the atrial communication created during transseptal passage of the Inoue balloon catheter on calculated mitral valve area after balloon valvotomy for severe mitral stenosis. Even in the absence of oxymetric evidence for a shunt, atrial septal puncture may result in left-to-right shunting of blood with reported spurious increases in postvalvotomy mitral valve area calculations ranging from 16-29% in prior studies. Occlusion of the septal puncture site after double balloon valvotomy has previously been shown to result in decreased postvalvotomy mitral valve area determinations. We evaluated 20 patients undergoing mitral dilation. Each patient had three postvalvotomy measurements made: (1) with the Inoue balloon catheter positioned across the septum, (2) during septal occlusion with a 7F balloon-tip catheter, and (3) without any catheters across the septum. With the Inoue catheter across the septum after successful valvotomy, the cardiac output was 4.6 +/- 1.5 L/min and the calculated mitral valve area was 1.7 +/- 0.5 cm2. No difference was found in either cardiac output or valve area when the septum was unobstructed by catheters. During septal occlusion, however, the postvalvotomy cardiac output decreased to 4.3 +/- 1.3 L/min (P < 0.001) and the calculated mitral area decreased by 12% to 1.5 +/- 0.5 cm2 (P < 0.001). The calculated mitral valve areas determined with the Inoue catheter in place after valvotomy were in agreement with echo derived data. Although statistically significant differences in post-Inoue valvotomy cardiac output and calculated mitral valve area were found during septal occlusion, these differences were small.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Output↗

Sustained reversal of right-to-left atrial septal defect flow after pulmonic valvuloplasty in an adult.

A 60-year-old man with Noonan's syndrome presented with generalized weakness, dyspnoea, and paresthesias. He was known to have pulmonic stenosis and atrial septal defect with right-to-left shunting and had refused therapy for many years. On presentation there was cyanosis and the haematocrit was 63%. After phlebotomy he was treated with balloon valvuloplasty. There was marked reduction in the transpulmonic gradient and oximetric evidence for reversal of his right-to-left atrial septal defect flow. After 18 months follow-up he remained system free and had no rise in haematocrit, consistent with no return of right-to-left shunting.

Catheterization↗

Valve resistance.

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Heart Valves↗

Hemodynamics of mitral stenosis: a review.

This review discusses the latest developments in the hemodynamics of mitral stenosis. English-language journal articles, reviews, and textbooks from the clinical, physiology, and engineering literature related to mitral valve stenosis were identified and reviewed. The main conclusions are: (1) the hemodynamics of mitral stenosis are determined by the complex anatomical and pathophysiologic features of the valve apparatus, (2) the properties of the left ventricle, atrium, and pulmonary vasculature also have a major impact on the hemodynamic significance and the clinical syndrome of mitral stenosis, (3) the valve and the cardiac chambers have a functional reserve that become exhausted as the stenosis worsens and/or the compensatory mechanisms of the chambers fail, and (4) a careful approach to data acquisition and analysis will lead to an accurate assessment of the hemodynamics of mitral stenosis before and after therapeutic interventions.

Atrial Function↗

Percutaneous mitral balloon valvotomy and the new demographics of mitral stenosis.

OBJECTIVE: This review discusses the latest developments in selected clinical features and catheter-based therapy of mitral stenosis. DATA SOURCES: English-language journal articles and reviews in the clinical and epidemiological literature as related to mitral valve stenosis from 1965 through March 1993, identified by bibliography review and expert consultation. STUDY SELECTION: Selected studies included clinical trials with adequate patient population description and short- and long-term (5 years) follow-up for topics related to mitral valve stenosis in the clinical literature. DATA EXTRACTION: Two reviewers participated in extracting the data with the aim of presenting a balanced and comprehensive review of the subject. DATA SYNTHESIS AND CONCLUSIONS: The main conclusions are (1) mitral stenosis should no longer be viewed as a largely "geriatric disease" in the United States due to a recent inflow many young immigrants from countries where rheumatic fever continues partially or wholly unabated; (2) clinical and anatomical features of mitral stenosis are age-dependent; when clinical presentation occurs at 30 vs 70 years of age, for example, the degree of valve obstruction may be similar but differences exist in the frequency of atrial fibrillation, the magnitude of reduction in cardiac output, the degree of valve deformity and calcification, and the frequency of coexistent coronary artery disease; and (3) mitral stenosis therapy has undergone a reorientation with the introduction of percutaneous mitral balloon valvotomy, which has proven to be safe, cost-effective, and to provide short- and long-term improvements in symptomatic and hemodynamic status in selected patients.

Catheterization↗

Serotype F double- and triple-converting phage insertionally inactivate the Staphylococcus aureus beta-toxin determinant by a common molecular mechanism.

The precise molecular mechanism of Staphylococcus aureus beta-toxin inactivation by the serotype F triple-converting phage phi 42, phi A1 and phi A3 was investigated. Sequence analysis of the phi 42 (attP) and Staphylococcus aureus (attB) attachment sites and the left (attL) and right (attR) chromosomal/bacteriophage DNA junctions of individual lysogens, each harbouring a triple-converting phage, revealed the presence of a common 14-bp core sequence in all four sites. These findings indicate that the genomes of the triple-converting phage integrate into the 5'-end of the beta-toxin gene (hlb) by a site- and orientation-specific mechanism identical to that previously described for the serotype F double-converting phage phi 13.

Attachment Sites, Microbiological↗

Effect of balloon size and stepwise inflation technique on the acute results of Inoue mitral commissurotomy. Inoue Balloon Catheter Investigators.

Currently percutaneous transvenous mitral commissurotomy (PTMC) is performed by most operators using stepwise inflation of the Inoue balloon beginning at a small diameter and increasing size by a sequence of inflations to nominal diameter. The effect of balloon size on procedure results using the Inoue balloon has not been evaluated. In 260 patients final balloon inflation was to nominal size in 42% of pts, larger than nominal size (overinflated) in 10%, and less than nominal size (underinflated) in 48% of pts. The average number of inflations was 3 (range 1-9). Pressure gradient and Doppler mitral regurgitation (MR) were assessed after each inflation. When MR increased, further inflations were not done. Patients in whom the balloon was overinflated underwent more balloon inflations than those in whom it was inflated to nominal size (5.0 +/- 2.1 vs. 2.9 +/- 1.4, p < 0.01). Those with balloon underinflation had fewer balloon inflations (2.4 +/- 1.2 vs. 2.9 +/- 1.4, p < 0.01). The post PTMC valve area in patients with overinflation was slightly less than those with nominal inflations (1.6 +/- 0.4 vs. 1.8 +/- 0.7), and with underinflation the valve area was no different compared to nominal inflation. Using a stepwise procedure, if mitral regurgitation was noted to increase after a balloon inflation, the procedure would be stopped even if less than an ideal result was achieved. Fewer inflations were done in patients in whom the balloon was inflated to less than nominal size because of the appearance of mitral regurgitation.(ABSTRACT TRUNCATED AT 250 WORDS)

Calibration↗

Restenosis following successful balloon valvuloplasty: bone formation in aortic valve leaflets.

Restenosis after balloon aortic valvuloplasty is common, occurring in as many as half or more of patients in the first year. To gain understanding of the mechanisms of restenosis we examined results of second dilatations and the histology of restenosed valves excised during valve replacement for restenosis. Eleven patients with calcific aortic stenosis underwent second valvuloplasty for restenosis. The mean age was 82 +/- 6 years. The interval between first and second dilatation was 14.7 +/- 8.5 months. First valvuloplasty resulted in an increase in valve area from 0.63 +/- 0.23 to 1.09 +/- 0.32 cm2 (p < 0.01). The valve area found after symptoms recurred was 0.56 +/- 0.18 cm2, not significantly different from the prevalvuloplasty dimensions. Second dilatation resulted in a mean aortic valve area of .76 +/- 0.22 cm2 (p = 0.011 vs results of first valvuloplasty). The change in valve area after first dilatation was 0.45 +/- 0.17 vs 0.20 +/- 0.13 cm2 after second dilatation (p < 0.01). Multiple histologic sections from excised, restenosed valves from five additional patients showed zones of active capillary and cellular proliferation and fibrosis in crevices between calcific nodules in three cases. Associated foci of ossification were seen in two of these. Stenotic nonvalvuloplasty control valves (n = 19) showed no ossifications. In conclusion, histologic changes in restenosed valves differ from those seen initially in calcific aortic stenosis, with granulation tissue, fibrosis, and ossification being present. These findings may help to explain the limited results of second dilatations for restenosis.

Aged↗

Cardiac catheterization and other imaging modalities in the evaluation of valvular heart disease.

This review describes recent publications using cardiac catheterization and diagnostic imaging modalities, excluding transesophageal and transthoracic echocardiography, to evaluate valvular heart disease. Radionuclide techniques and magnetic resonance imaging continue to be studied as to whether they can improve the quantification of valvular regurgitation. As yet, however, they are not justified in the routine evaluation of patients with valvular heart disease. Cardiac catheterization has been used by several authors to assess more completely the obstructive physiology of valve stenosis, including obtaining a better understanding of transvalvular pressure gradients; the phenomenon of downstream pressure recovery; and the utility of valve resistance in quantifying the severity of the valve stenosis, which complements the calculated valve area, especially in cases of low cardiac output. Traditional cardiac catheterization techniques have recently been used to show a sex difference in left ventricular systolic performance in aortic stenosis. Intracardiac ultrasound and electrocardiography are being studied as methods to guide percutaneous valvotomy. The analysis of myocardial tissue samples obtained by endocardial biopsy promises understanding gene-protein-function interactions. Specifically, myosin alterations in aortic valve disease and protooncogene expression in hypertrophy are exciting, emerging areas of investigation.

Biopsy↗

Multidimensional scaling of painful electrocutaneous stimulation: INDSCAL dimensions, signal detection theory indices, and the McGill Pain Questionnaire.

Individual-differences multidimensional scaling (INDSCAL) determined the dimensions underlying ratings of electrocutaneous stimuli, which ranged from innocuous levels to individual pain intolerance at each of three frequencies. Twenty-five healthy males made pairwise similarity judgments of these 15 stimuli for the INDSCAL procedure, and then rated each stimulus on nine property scales. Signal detection theory indices, as well as ratings on the McGill Pain Questionnaire (MPQ), were also obtained. A Sensory Magnitude dimension scaled the stimuli from lowest to highest perceived intensity; this dimension was related to sensory, affective, and arousal property scales. A Frequency dimension ordered the stimuli from lowest to highest frequency; this dimension was related to the Fast-Slow property. Compared to the Frequency dimension, the Sensory Magnitude dimension was more salient to subjects who better discriminated among painful stimulus intensities, set a more stoical pain report criterion, and were less apt to endorse frequency-related MPQ descriptors. Thus, variation of physical intensity and frequency elicited complementary dimensions of subjective judgment, which were related to perceptual and attitudinal differences among individuals.

Adolescent↗

Turbulence intensity in aortic stenosis: frequency characteristics and effects of alterations in left ventricular function.

Turbulent blood flow can occur downstream from a stenosis. The purpose of this study was to quantitate turbulence intensity and its frequency characteristics in the ascending aorta in adult patients with and without valvular stenosis, and to use extrasystoles to analyze the effects of changes in left ventricular function on turbulence. Turbulence intensity was determined from the digitized, high frequency oscillations seen in high fidelity pressure recordings of 25 patients with valvular aortic stenosis. The intensity of turbulence was quantitated as the root-mean-square (mmHg) of pressure fluctuations and as the total spectral power (mmHg2/beat) of the frequency spectrum between 25 Hz and 400 Hz. Frequency characteristics were summarized by the mean and median frequency of spectral power and partitioning the spectrum into 25 Hz segments. Ten adult patients without aortic valve or outflow tract abnormalities served as controls. Adult patients with aortic stenosis had significantly more turbulence in the ascending aorta than controls (total spectral power 1577 +/- 450 mmHg2 vs. 198 +/- 22 mmHg2, p < 0.01). Furthermore, the frequency distribution in aortic stenosis was biased towards higher frequencies (mean frequency 35 +/- 14 Hz vs 54 +/- 2 Hz, p < 0.001). Turbulence intensity in aortic stenosis demonstrated beat to beat modulation by left ventricular function. The total spectral power of a sinus beat was 1888 +/- 762 mmHg2, and fell to 137 +/- 63 mmHg2 in a weak premature beat, and rose to 3618 +/- 1178 mmHg2 in a potentiated post- extrasystolic beat (p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗