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Biomedical subjects

D A Morrison

Publications and source records attributed to D A Morrison.

At least 109 records · Page 6Linked to original sources

Identification of two proteins encoded by com, a competence control locus of Streptococcus pneumoniae.

The com locus, which controls competence for genetic transformation in Streptococcus pneumoniae, was analyzed by construction of a series of subclones, insertion mutations, and deletions of the cloned DNA in Escherichia coli. In vitro transcription-translation of these com plasmids revealed two neighboring genes, comA and comB, encoding proteins of 77,000 and 49,000 daltons, respectively. Their map positions and orientations were determined. Insertions in either gene eliminated the corresponding protein and had no effect on the other. In addition, a 15,000-dalton com protein was tentatively identified, although the exact location of this gene remains to be determined. Features of the DNA adjacent to the com locus are also described.

Bacterial Proteins↗

Cloning of Streptococcus pneumoniae DNA fragments in Escherichia coli requires vectors protected by strong transcriptional terminators.

Unstable recombinant plasmids are frequently encountered when cloning pneumococcal DNA into ordinary Escherichia coli plasmid vectors (e.g., pBR325, pMB9, pHC79). Stassi and Lacks [Gene 18 (1982) 319-328] have shown that the pneumococcal mal region, which exhibits strong promoter activity, interferes with maintenance of a recombinant plasmid in E. coli. In this paper, we report that random pneumococcal DNA fragments cloned in E. coli exhibited a higher frequency of strong promoter activity than did similarly cloned E. coli fragments. Furthermore, shotgun cloning yields for pneumococcal DNA were found to be higher with cloning vectors containing efficient transcriptional terminators surrounding the insertion site than with vectors lacking such protection. Therefore, vectors which carry an efficient transcriptional terminator are likely to be valuable for cloning pneumococcal DNA and stabilizing the recombinants. A new vector, pJDC9, was constructed, containing a lacZ alpha' multiple cloning site surrounded by transcriptional terminators, and an erythromycin-resistant marker expressed both in E. coli and Streptococcus. This plasmid was shown to be unusually effective for cloning of streptococcal genes in E. coli, and is designed to permit excisional cloning of streptococcal DNA in E. coli.

Cloning, Molecular↗

Right ventricular dysfunction and the exercise limitation of chronic obstructive pulmonary disease.

This study examined right ventricular function during exercise in patients with chronic obstructive pulmonary disease to answer the following questions: Is there a significant correlation between oxygen consumption at maximal exercise and exercise right ventricular ejection fraction? Does the right ventricular ejection fraction response to exercise correlate with exercise changes in pulmonary artery pressure, total pulmonary resistance or pulmonary vascular resistance? Which combinations of cardiac, ventilatory and blood gas variables are the best predictors of oxygen consumption at maximal exercise? Twenty-six patients with stable chronic obstructive pulmonary disease performed symptom-limited supine bicycle exercise with simultaneous hemodynamic and radionuclide ventriculographic measurements. The oxygen consumption at maximal exercise correlated with the exercise right ventricular ejection fraction (n = 21, r = 0.66; p less than 0.005), exercise stroke volume (r = 0.68; p less than 0.001), exercise cardiac output (r = 0.77; p less than 0.00005) and exercise ventilation (r = 0.85; p less than 0.00001). The change in right ventricular ejection fraction from rest to exercise correlated inversely with the change from rest to exercise in total pulmonary resistance (r = -0.51; p less than 0.05) but not with the change in mean pulmonary pressure (r = -0.37) or in pulmonary vascular resistance (r = 0.09). Multivariate analysis showed that the variables giving the highest combined correlation with oxygen consumption were ventilation and right ventricular ejection fraction (r = 0.95, adjusted r2 = 0.88). These results suggest that exercise oxygen consumption of patients with chronic obstructive pulmonary disease is related to right ventricular systolic function, exercise right ventricular dysfunction is related, in part, to abnormal exercise total pulmonary resistance, and exercise limitation in chronic obstructive pulmonary disease occurs as a result of the dynamic interaction between disordered right heart function and ventilation.

Adult↗

Modulation of competence for genetic transformation in Streptococcus pneumoniae.

The spontaneous development of competence by cultures of Streptococcus pneumoniae in casein hydrolysate medium was strongly dependent on the initial pH of the culture medium. Cells growing in cultures beginning with a wide range of initial pH values (6.8 to 8.0) all developed competence, as measured by [3H]DNA uptake, [3H]DNA degradation and genetic transformation; but the initial pH of the medium affected both the timing of the occurrence of competence and the number of times the culture became competent. In cultures grown in media of lower initial pH, competence occurred only once, at high population densities, while in more alkaline media a succession of competence cycles occurred, beginning at lower cell densities. The critical population density required for the initiation of competence varied tenfold over the pH range studied. Successive competence cycles in an alkaline medium were not equivalent: while the percentage of competent cells in the first competence cycle was high (approximately 80%), that in the second competence cycle was lower (approximately 12%). Correspondingly, competence-specific proteins were less prominent in the labelled-protein pattern of the second competence cycle than in that of the first. These features of the physiology of competence control make it possible to adjust the expression of competence to suit various experimental requirements.

DNA, Bacterial↗

Competence for genetic transformation in Streptococcus pneumoniae: molecular cloning of com, a competence control locus.

To identify and map genes involved in competence for genetic transformation in Streptococcus pneumoniae, we have cloned DNA surrounding an ermB insertion mutation that causes a competence factor deficiency. We recovered the insert and approximately 500 base pairs of neighboring pneumococcal DNA in pMB9. Larger pieces of DNA from this region were unstable in pMB9 and pBR325. However, larger pieces were stable in pKK232-8, an Escherichia coli vector containing strong transcription terminators. Overlapping pieces of wild-type DNA from this competence control region were cloned and mapped in this vector. Insertion mutations were constructed in vitro throughout the cloned region. When crossed into the pneumococcus chromosome, they showed that the com locus was 4.2 to 5.2 kilobases long.

Bacterial Proteins↗

Radionuclide and angiographic assessment of the right heart.

Although the pleomorphic nature of the human right ventricle makes wall motion assessment a challenge, it is a worthy challenge in terms of recognizing clinical infarction, ischemia, and primary contractile abnormalities of the right heart. As for the left ventricle, contrast angiography provides the best frame of reference, but will hopefully make way for noninvasive radionuclide ventriculographic methods after systemic evaluation has been carried out.

Heart↗

Effects of aerobic training on exercise tolerance and echocardiographic dimensions in untrained postmenopausal women.

The cardiovascular effects of physical training were evaluated in a controlled trial involving 32 healthy, untrained, postmenopausal women. The subjects were randomly assigned to an aerobic exercise training program or a control group. The exercise group participated in at least three 40-minute supervised sessions per week for 8 months. Twenty-five subjects completed the study: eight in the control group and 17 in the training group. The training group had a significant increase over the training period in maximal oxygen consumption (27.3 +/- 4.6 ml/kg/min vs 30.8 +/- 5.4 ml/kg/min, p less than 0.05) and maximal treadmill exercise duration (9.8 +/- 2.6 minutes vs 11.3 +/- 2.2 minutes; p less than 0.05). The control group had no significant change in maximal treadmill exercise duration (9.0 +/- 1.2 minutes vs 9.2 +/- 1.4 minutes) but had a slight increase in maximal oxygen consumption (23.7 +/- 3.4 ml/kg/min vs 24.4 +/- 4.1 ml/kg/min, p less than 0.05). The training group had significant increases in M-mode echocardiographic left ventricular end-diastolic dimension (4.6 +/- 0.6 cm vs 4.8 +/- 0.4 cm, p less than 0.05) and calculated left ventricular ejection fraction (0.66 +/- 0.14 vs 0.74 +/- 0.12, p less than 0.05). M-mode echocardiograms demonstrated no significant change in left ventricular dimensions or wall thickness in the control group. In this group of untrained postmenopausal women, a training effect was associated with enhanced resting left ventricular ejection fraction and increased resting left ventricular end-diastolic dimension.

Adaptation, Physiological↗

Localization of competence-induced proteins in Streptococcus pneumoniae.

Intracellular locations of 11 proteins associated with the development of competence in Streptococcus pneumoniae were examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of subcellular fractions prepared from protoplasts. Controls showed that the competence-induced proteins were stable during the formation of protoplasts at 25 degrees C even though some had a half-life of only 8 min at 37 degrees C. Five competence-induced proteins p38, p27, p19.5, p16, and p14.5, were found in the cytoplasm. Two, p52 and p41, were associated with the membrane, and one, p10, was extracellular. Three others, p50, p36, and p29, were recovered in both cytoplasmic and membrane fractions. No competence-induced protein was detected in the periplasmic fraction except under conditions where leakage of all components was occurring, a phenomenon that was seen in many preparations. Similar fractionation of competent cells soon after uptake of [3H]DNA showed the "eclipse complex" of single-stranded DNA and p19.5 was associated approximately one-third with membranes and two-thirds with cytoplasmic fractions, with almost none in the periplasm. This result suggests strongly that at the time the donor DNA entered the cytosol it was in single-stranded form and it had not yet paired with the recipient DNA.

Bacterial Proteins↗

Oral progesterone treatment in chronic obstructive lung disease: failure of voluntary hyperventilation to predict response.

Previous studies have shown that some patients with chronic obstructive lung disease and hypercapnia will respond to medroxyprogesterone with improvement in arterial blood gases. The exact mechanism of this effect is unclear but it is presumed to be a result of ventilatory stimulation. To determine whether the ability to correct arterial blood gas abnormalities by voluntary hyperventilation would predict a subsequent favourable response to progesterone, we studied 11 subjects with chronic obstructive lung disease and chronic hypercapnia. Five subjects had chronic obstructive lung disease of moderate severity with mean (SE) FEV1 1.8 (0.34) 1 maximum voluntary ventilation (MVV) 40.4 (7.16) 1/min-1, arterial oxygen tension (Pao2) 53.8 (2.40 mm Hg, and arterial carbon dioxide tension Paco2) 49.6 (3.91) mm Hg, and were able to normalise their blood gas tensions during voluntary hyperventilation (Pao2 85.4 (8.01) mm Hg; Paco2 32.8 (3.43) mm Hg). Six subjects had severe chronic obstructive lung disease with FEV1 0.77 (0.12) 1, MVV 19 (3.09) 1/min-1, Pao2 60.0 (2.89) mm Hg and Paco2 50.5 (1.38) mm Hg, and they could not significantly alter their blood gases with voluntary hyperventilation (Pao2 62.5 (3.19) mm Hg, Paco2 49.7 (1.84) mm Hg). The groups were similar in age, height, weight, and resting Pao2 and Paco2. Each subject received one month of oral placebo and one month of medroxyprogesterone acetate (Provera). 20 mg orally thrice daily, given in a randomised, double blind fashion. The groups responded similarly with a significantly higher Pao2 and lower Paco2 while having medroxyprogesterone acetate than while having placebo. Two patients with polycythaemia showed a reduction in haemoglobin concentration while taking progesterone. It is concluded that the response to medroxyprogesterone is not predictable from spirometric or blood gas changes after voluntary hyperventilation.

Blood Gas Analysis↗

Preliminary study of the effects of low flow oxygen on oxygen delivery and right ventricular function in chronic lung disease.

This study was designed to test the feasibility of using the noninvasive radionuclide measurement of the right ventricular ejection fraction (RVEF) to identify which patients with chronic lung disease objectively benefit from low flow oxygen therapy. Two categories of benefit, pulmonary artery pressure/resistance and peripheral oxygen delivery, were examined in 19 patients. Fourteen subjects returned after at least 3 wk of continuous low flow oxygen therapy for restudy; 12 patients had complete radionuclide and hemodynamic data. The change in RVEF, in response to continuous oxygen, correlated significantly with the change in coefficient of oxygen delivery (r = 0.59, p less than 0.05) and the change in cardiac output (r = 0.62, p less than 0.05). The change in RVEF did not correlate significantly with the change in pulmonary artery pressure (r = 0.06) or the change in total pulmonary resistance (r = -0.35). The change in coefficient of oxygen delivery, representing oxygen delivery corrected for oxygen consumption, correlated positively with change in cardiac output (r = 0.58, p less than 0.05) and negatively with change in oxygen consumption (r = -0.63, p less than 0.05), arterial oxygen content (r = -0.63, p less than 0.05), and arterial oxygen tension (r = -0.61, p less than 0.05). That is, the fall in hemoglobin in these patients more than compensated for any increase in Pao2 so that improved oxygen delivery frequently occurred despite a decrease in arterial oxygen content, and improved oxygen delivery occurred for the most part among patients with smaller improvement in Pao2.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Severe pulmonary hypertension in a patient with Whipple's disease.

Rapidly progressive heart failure, in part related to severe pulmonary hypertension, developed in a patient with biopsy-proved Whipple's disease. The patient's pulmonary hypertension progressed despite antibiotic therapy and histologic remission of his intestinal disease. The combination of oral nifedipine and low-flow continuous oxygen led to both short- and long-term increases of at least 2 liters per minute in cardiac output and reductions of more than 10 mm Hg in mean pulmonary artery pressure. Accompanying these hemodynamic changes was an improvement of more than 10 percent in right ventricular ejection fraction. The relationship between this patient's pulmonary hypertension and his Whipple's disease is not known.

Drug Combinations↗

Right ventricular function at rest and during exercise in aortic and mitral valve disease.

Right ventricular function at rest and during exercise was examined in a group of patients with symptomatic aortic or mitral valve disease, or both. The right ventricular ejection fraction was less than 45% in 22 of 36 patients at rest and in 12 of 17 subjects at symptom-limited, supine bicycle exercise. The right ventricular ejection fraction failed to increase more than 5% with exercise in 17 of 17 patients. The central venous pressure was greater than 5 mm Hg in 18 of 36 patients at rest and in 13 of 17 patients at maximal exercise. There was a significant inverse relation between rest right ventricular ejection fraction and mean pulmonary artery pressure (r = -0.47, p less than 0.05) and between rest right ventricular ejection fraction and mean central venous pressure (r = -0.39, p less than 0.05). There was no significant relation between the exercise values of these variables. In individual patients, the changes in right ventricular ejection fraction and pulmonary artery pressure with graded exercise were nonlinear. It is concluded that right ventricular function is not a simple function of pulmonary artery pressure at rest or during exercise in aortic and mitral valve disease. Less than one-quarter of the variation in right ventricular ejection fraction at rest can be explained by the variation in pulmonary artery pressure, and the finding of a normal (greater than 45%) right ventricular ejection fraction does not reliably exclude the possibility of pulmonary hypertension in a patient with valvular heart disease.

Adult↗

Right ventricular ejection fraction measurement: contrast ventriculography versus gated blood pool and gated first-pass radionuclide methods.

Radionuclide methods of measuring the right ventricular (RV) ejection fraction (EF) provide noninvasive means of evaluating right-sided cardiac function at rest and exercise. This study compared 2 radionuclide methods with a cast-validated contrast angiographic method of RVEF analysis in 21 consecutive patients who underwent RV contrast ventriculography and gated equilibrium blood pool radionuclide ventriculography. Eleven subjects had gated first-pass radionuclide studies that were technically adequate for EF analysis. RVEF was calculated by different operators for the contrast and radionuclide methods. The close correlation of the contrast angiographic method with both equilibrium blood pool and first-pass radionuclide methods supports the use of the radionuclide techniques.

Adult↗

Surveillance of stage O, grade I bladder cancer by cytology alone--is it acceptable?

Although the high incidence of subsequent tumors is well established there is accumulating evidence that few cases of low grade, low stage transitional cell carcinomas will progress in stage. Since the purpose of intensive endoscopic monitoring following initial tumor resection is to detect potentially lethal new tumors as soon as possible, we reviewed retrospectively the course of 36 patients with an initial grade I, stage O (Ta) transitional cell carcinoma to determine whether cytology was capable of achieving this goal. Of these patients 10 (28 per cent) had a subsequent tumor of a higher grade or stage. Cytology performed at or before recurrence was positive in 8 patients (80 per cent) and 2 (20 per cent) had grade II, noninvasive transitional cell carcinoma with negative cytology. Subsequent tumors in these 2 patients have been grade I. All 36 patients are alive. Given the patient inconvenience, expense and risk of infection of cystoscopy compared to cytology, this retrospective review suggests that when an experienced cytopathologist is available patients with grade I, noninvasive transitional cell carcinoma may be monitored primarily by urinary cytology with less frequent endoscopy. A prospective study must be performed to confirm this approach.

Aged↗

Gated first pass radionuclide ventriculography. Methods, validation, and applications.

Electrocardiographic gating provides an alternative method of acquiring first pass radionuclide ventriculograms from both ventricles. This report details the methods of acquisition and analysis, provides validation and reproducibility data, and describes applications of gated first pass radionuclide ventriculography using a count-based method. Left ventricular ejection fractions measured by gated first pass were correlated quite closely with gated blood pool ventriculography (n = 43; r = 0.95) but less well with contrast angiography (n = 23; r = 0.72). The right ventricular ejection fractions measured by gated first pass compared favorably with gated blood pool ventriculography (n = 32; r = 0.93). When one observer processed the images two times, the reproducibilities of RVEF (n = 10; r = 0.99) and LVEF (n = 10; r = 0.88) were excellent. Similarly, when two observers processed the images independently, the reproducibilities of RVEF (n = 11; r = 0.99) and LVEF (n = 11; r = 0.98) were excellent. The first pass studies were obtained in a right anterior obliquity, which provided the best atrioventricular chamber separation and provided a different view of global ventricular function and segmental wall motion from that provided by the standard blood pool views.

Adolescent↗

Isolation of transformation-deficient Streptococcus pneumoniae mutants defective in control of competence, using insertion-duplication mutagenesis with the erythromycin resistance determinant of pAM beta 1.

Several transformation-deficient mutants of Streptococcus pneumoniae were isolated after insertion-duplication mutagenesis. Mutagenesis was accomplished by transformation of competent cells with chimeric DNA formed by the ligation of TaqI fragments of pneumococcal DNA to the erythromycin resistance determinant of the streptococcal plasmid pAM beta 1. The two mutants described were characterized as defective in the control of competence induction, possibly due to a block in the production of the intercellular competence-inducing protein.

Chimera↗

Pastoral care personnel have prophetic role.

Pastoral care ministers must look to the prophet's role in the Old and New Testaments to establish their own prophetic mission in health care facilities. After evaluating whether their own department acts justly, competently, and compassionately, pastoral care givers must hold themselves accountable to the signs of authentic prophecy: being motivated by love, being critical to promote constructive change, and being willing to confront others' resistance. Then the pastoral care team can begin collaborating with peers to provide a more healing environment for all staff and patients. This can be done by being available to help staff with problems, influencing policymaking, and using ministerial skills when giving sacramental care to patients. Pastoral care persons can link the facility to the outside community by finding ways to reach the needy and to address residents' unmet health needs. Eventually the pastoral care staff and their peers can work toward an active response to social justice. The challenge of being prophets requires pastoral care personnel to confront problems courageously and take advocacy positions while always showing compassion.

Altruism↗