Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 42
Filter
1.
Clin Pharmacol Ther ; 93(4): 326-34, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23361105

ABSTRACT

Bradykinin increases during cardiopulmonary bypass (CPB) and stimulates the release of nitric oxide, inflammatory cytokines, and tissue-type plasminogen activator (t-PA), acting through its B2 receptor. This study tested the hypothesis that endogenous bradykinin contributes to the fibrinolytic and inflammatory response to CPB and that bradykinin B2 receptor antagonism reduces fibrinolysis, inflammation, and subsequent transfusion requirements. Patients (N = 115) were prospectively randomized to placebo, ε-aminocaproic acid (EACA), or HOE 140, a bradykinin B2 receptor antagonist. Bradykinin B2 receptor antagonism decreased intraoperative fibrinolytic capacity as much as EACA, but only EACA decreased D-dimer formation and tended to decrease postoperative bleeding. Although EACA and HOE 140 decreased fibrinolysis and EACA attenuated blood loss, these treatments did not reduce the proportion of patients transfused. These data suggest that endogenous bradykinin contributes to t-PA generation in patients undergoing CPB, but that additional effects on plasmin generation contribute to decreased D-dimer concentrations during EACA treatment.


Subject(s)
Aminocaproic Acid/therapeutic use , Blood Transfusion/statistics & numerical data , Bradykinin Receptor Antagonists , Bradykinin/analogs & derivatives , Bradykinin/physiology , Cardiopulmonary Bypass/adverse effects , Fibrinolysis/physiology , Inflammation/drug therapy , Antifibrinolytic Agents/therapeutic use , Bradykinin/antagonists & inhibitors , Bradykinin/therapeutic use , Female , Fibrin Fibrinogen Degradation Products/metabolism , Fibrinolysis/drug effects , Humans , Male , Middle Aged , Postoperative Complications , Postoperative Hemorrhage/drug therapy
2.
Clin Pharmacol Ther ; 91(6): 1065-73, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22549281

ABSTRACT

The effects of angiotensin-converting enzyme (ACE) inhibition and angiotensin II type 1 receptor blockade (ARB) on fibrinolysis and inflammation after cardiopulmonary bypass (CPB) are uncertain. This study tested the hypothesis that ACE inhibition enhances fibrinolysis and inflammation to a greater extent than ARB in patients undergoing CPB. One week to 5 days before surgery, patients were randomized to ramipril 5 mg/day, candesartan 16 mg/day, or placebo. ACE inhibition increased intraoperative bradykinin and tissue-type plasminogen activator (t-PA ) concentrations as compared to AR B. Both ACE inhibition and AR B decreased the need for plasma transfusion relative to placebo, but only ACE inhibition decreased the duration of hospital stay. Neither ACE inhibition nor AR B significantly affected concentrations of plasminogen activator inhibitor-1 (PAI -1), interleukin (IL )-6, IL -8, or IL -10. ACE inhibition enhanced intraoperative fibrinolysis without increasing the likelihood of red-cell transfusion. By contrast, neither ACE inhibition nor ARB affected the inflammatory response. ACE inhibitors and ARBs may be safely continued until the day of surgery.


Subject(s)
Angiotensin II Type 1 Receptor Blockers/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Benzimidazoles/therapeutic use , Cardiopulmonary Bypass/adverse effects , Fibrinolysis/drug effects , Inflammation/drug therapy , Ramipril/therapeutic use , Tetrazoles/therapeutic use , Aged , Biphenyl Compounds , Blood Transfusion , Bradykinin/metabolism , Endpoint Determination , Female , Hematocrit , Hospital Mortality , Humans , Inflammation/etiology , Interleukins/metabolism , Length of Stay , Male , Middle Aged , Monitoring, Intraoperative , Perioperative Care , Postoperative Complications/epidemiology , Treatment Outcome
3.
J Heart Valve Dis ; 10(4): 436-42, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11499586

ABSTRACT

BACKGROUND AND AIM OF THE STUDY: The St. Jude Medical (SJM) Regent heart valve is a new bileaflet prosthetic valve modified from the currently marketed SJM mechanical valve, with a modified external profile that results in a larger geometric orifice area without changing the existing design of the pivot mechanism or blood contact surface areas. The aim of the present study was to report the early hemodynamic and clinical results of an on-going multicenter trial investigating the clinical performance of the Regent mechanical aortic valve prosthesis. METHODS: The early results from 204 patients at 11 centers in North America and Europe who underwent implantation of a Regent mechanical aortic valve prosthesis are described. Clinical status was prospectively recorded, and echocardiography with Doppler performed at hospital discharge, and at two and six months and one year postoperatively. RESULTS: Follow up to date is 109.3 patient-years (average follow up 0.5+/-0.4 years per patient; range: 0 to 1.7 years). NYHA class improved for the group, and there were low rates of clinical adverse effects. Echocardiographic mean pressure gradient at six months was 13.8+/-10.3, 7.4+/-4.1, 5.4+/-3.2, 5.2+/-2.8, 3.4+/-2.3 and 3.6 mmHg, respectively, for 19, 21, 23, 25, 27 and 29 mm valves; effective orifice area was 1.5+/-0.6, 2.0+/-0.7, 2.4+/-1.0, 2.5+/-0.7, 3.6+/-1.4 and 4.8 cm2, respectively. There was a statistically significant decrease in left ventricular mass index between early postoperative (169.1+/-57.7 g/m2) and six months follow up (137.2+/-42.7 g/m2, delta = -30.1+/-42.5 g/m2, p <0.0001). CONCLUSION: The SJM Regent aortic valve has excellent associated hemodynamics with rapid and significant left ventricular mass regression. In all cases of adverse events, rates fell within Objective Performance Criteria guidelines. Long-term clinical assessment is on-going.


Subject(s)
Aortic Valve Insufficiency/physiopathology , Aortic Valve/physiopathology , Heart Valve Prosthesis , Hemodynamics , Aged , Aged, 80 and over , Aortic Valve/diagnostic imaging , Aortic Valve/surgery , Aortic Valve Insufficiency/diagnostic imaging , Aortic Valve Insufficiency/surgery , Echocardiography, Doppler , Equipment Design , Europe , Female , Follow-Up Studies , Humans , Male , Middle Aged , North America , Postoperative Period , Prospective Studies
4.
Ann Thorac Surg ; 71(5 Suppl): S302-5, 2001 May.
Article in English | MEDLINE | ID: mdl-11388210

ABSTRACT

BACKGROUND: Hemodynamic benefits of the Toronto stentless porcine valve have been documented. Clinical well-being and freedom from major valve-related events have been less well defined. METHODS: A total of 447 patients were prospectively followed for up to 8 years (1,745.2 valve years total, 3.9 valve years/patient). The patient demographics included 66% men, mean age 65 years, New York Heart Association functional class III-IV 55%, concomitant coronary artery bypass grafting 41%. RESULTS: We found that 83.7% of patients were in New York Heart Association functional class I and 80.8% had 0 to 1+ aortic insufficiency. Mean gradient at 6 years (n = 75) was 4.4 mm Hg and mean effective orifice area (EOA) 2.4 cm2. Late adverse event rates per patient per year were: embolism 1.0%, endocarditis 0.4%, thrombosis 0%, structural deterioration 0.2%, explant 0.3%, and valve-related death 0.6%. Freedom from valve-related death at 6 years was 95.8%; from cardiac death 96.3%. Freedom from endocarditis was 98.4%, from embolism 93.9%, from structural deterioration 97.4%, and freedom from explant 98.1%. For patients older than 60 years, freedom from structural deterioration was 100%. CONCLUSIONS: These results confirm satisfactory clinical outcomes after aortic valve replacement with the Toronto stentless porcine valve, with a low incidence of valve-related adverse events as long as 96 months after valve replacement.


Subject(s)
Aortic Valve/surgery , Bioprosthesis , Heart Valve Prosthesis , Adult , Aged , Aged, 80 and over , Aortic Valve Insufficiency/mortality , Aortic Valve Insufficiency/surgery , Cause of Death , Female , Follow-Up Studies , Humans , Male , Middle Aged , Postoperative Complications/mortality , Prospective Studies , Prosthesis Failure , Stents , Survival Rate
5.
Plant Physiol ; 125(2): 770-8, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11161034

ABSTRACT

Ferredoxin-1 (Fed-1) mRNA contains an internal light response element (iLRE) that destabilizes mRNA when light-grown plants are placed in darkness. mRNAs containing this element dissociate from polyribosomes in the leaves of transgenic tobacco (Nicotiana tabacum) plants transferred to the dark for 2 d. Here, we report in vivo labeling experiments with a chloramphenicol acetyl transferase mRNA fused to the Fed-1 iLRE. Our data indicate that the Fed-1 iLRE mediates a rapid decline in translational efficiency and that iLRE-containing mRNAs dissociate from polyribosomes within 20 min after plants are transferred to darkness. Both events occur before the decline in mRNA abundance, and polyribosome association is rapidly reversible if plants are re-illuminated. These observations support a model in which Fed-1 mRNA in illuminated leaves is stabilized by its association with polyribosomes, and/or by translation. In darkness a large portion of the mRNA dissociates from polyribosomes and is subsequently degraded. We also show that a significant portion of total tobacco leaf mRNA is shifted from polyribosomal to non-polyribosomal fractions after 20 min in the dark, indicating that translation of other mRNAs is also rapidly down-regulated in response to darkness. This class includes some, but not all, cytoplasmic mRNAs encoding proteins involved in photosynthesis.


Subject(s)
5' Untranslated Regions/genetics , Ferredoxins/genetics , Nicotiana/genetics , Pisum sativum/genetics , Protein Biosynthesis/radiation effects , RNA, Messenger/genetics , Darkness , Light , Pisum sativum/radiation effects , Plant Leaves/genetics , Plant Leaves/metabolism , Plants, Genetically Modified/genetics , Plants, Genetically Modified/radiation effects , Polyribosomes/genetics , Nicotiana/radiation effects
6.
Semin Thorac Cardiovasc Surg ; 13(4 Suppl 1): 173-9, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11805968

ABSTRACT

The hemodynamic performance of stentless aortic bioprostheses has been well described during the first few months after surgery. The purpose of the present study was to describe the hemodynamic performance of the Toronto SPV valve (St. Jude Medical, Inc, St. Paul, MN) in a multicenter trial through 8 years. The long-term study of the Toronto SPV valve includes 447 consecutive patients from 6 investigative centers. Echocardiographic follow-up was performed at specified intervals, with quantitative analysis performed at a centralized core laboratory. Mean transvalvular gradient decreased significantly between discharge and 6 months, between 6 months and 1 year, and between 1 year and 2 years after surgery, without further significant change. The effective orifice area increased significantly early after surgery and continued to increase through 6-year follow-up. The left ventricular (LV) stroke volume increased progressively from discharge through 6-year follow-up. The LV mass index decreased significantly from discharge through 3 years after surgery and stabilized through 5 years. There was a gradual increase in LV outflow tract diameter between 1 year and 6 years after surgery. The prevalence of any aortic regurgitation (AR) (including trivial) and > or = mild AR increased significantly between discharge and 6-year to 8-year follow-up. However, the prevalence of > or = moderate AR remained very low at 6 years (2.6%) and 8 years (4.5%) after surgery. In conclusion, the Toronto SPV stentless tissue aortic valve is associated with excellent hemodynamics early after surgery and through 8 years after surgery. LV mass decreases early, and returns to within the range of normal by 1 year after surgery. There is evidence of continued LV mass regression involving the LV outflow tract, potentially contributing to a small but significant late improvement in hemodynamics. The prevalence of significant AR remains low through 8 years.


Subject(s)
Aortic Valve Insufficiency/etiology , Aortic Valve/surgery , Bioprosthesis , Heart Valve Prosthesis , Postoperative Complications , Ventricular Function, Left/physiology , Adult , Aged , Aortic Valve/diagnostic imaging , Aortic Valve Insufficiency/epidemiology , Echocardiography , Female , Follow-Up Studies , Heart Valve Diseases/surgery , Hemodynamics , Humans , Male , Middle Aged , Postoperative Period , Prevalence
7.
Plant J ; 21(6): 563-9, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10758507

ABSTRACT

Ferredoxin-1 (Fed-1) mRNA is poorly translated in dark-treated tobacco (Nicotiana tabacum) leaves, resulting in destabilization of Fed-1 mRNA and a differential light/dark accumulation of the mRNA. Insertion of nonsense codons within the Fed-1 coding sequence disrupts the light regulation of Fed-1 mRNA abundance. Here we show that the nonsense codon effect results primarily from lowering the Fed-1 mRNA stability in light-treated leaf tissue and in rapidly growing tobacco cell cultures, but not in dark-treated leaf tissue. These results suggest that nonsense codons trigger a decay pathway distinct from that seen for Fed-1 mRNA in the dark. We propose that nonsense-mediated decay of nonsense-containing Fed-1 mRNA occurs in light-treated leaves and in non-photosynthetic tobacco culture cells where Fed-1 mRNA is being actively translated.


Subject(s)
Codon, Terminator , Ferredoxins/genetics , Pisum sativum/genetics , Protein Biosynthesis , RNA, Messenger/metabolism , Cells, Cultured , Mutation , Pisum sativum/metabolism
8.
Genet Eng (N Y) ; 22: 1-10, 2000.
Article in English | MEDLINE | ID: mdl-11501372

ABSTRACT

A significant number of studies have detected a post-transcriptional component in the light responses of nuclear genes. As yet there are few in-depth studies of the mechanism(s) involved, and it seems likely some additional examples have been missed. For instance, transcriptional responses have sometimes been inferred on the basis of experiments with translational fusions containing both the promoter and 5' UTR of the test gene, but we now know that elements within the 5' UTR can mediate post-transcriptional light responses. Similarly, because of possible changes in translation rates and protein turnover, the common assumption that mRNA levels directly dictate protein levels is tenuous at best. It is no longer permissible to assume that the biological effect of a gene is a simple function of its transcription. Thus it is likely that with careful experimental design, reports of nuclear-encoded post-transcriptional gene regulation will become increasingly prevalent.


Subject(s)
Light , Plants/genetics , RNA Processing, Post-Transcriptional , Cell Nucleus/genetics , Gene Expression Regulation, Plant
9.
N Engl J Med ; 341(14): 1029-36, 1999 Sep 30.
Article in English | MEDLINE | ID: mdl-10502592

ABSTRACT

BACKGROUND: Transmyocardial revascularization involves the creation of channels in the myocardium with a laser to relieve angina. We compared the safety and efficacy of transmyocardial revascularization performed with a holmium laser with those of medical therapy in patients with refractory class IV angina (according to the criteria of the Canadian Cardiovascular Society). METHODS: In a prospective study conducted between March 1996 and July 1998 at 18 centers, 275 patients with medically refractory class IV angina and coronary disease that could not be treated with percutaneous or surgical revascularization were randomly assigned to receive transmyocardial revascularization followed by continued medical therapy (132 patients) or medical therapy alone (143 patients). RESULTS: After one year of follow-up, 76 percent of the patients who had undergone transmyocardial revascularization had improvement in angina (a reduction of two or more classes), as compared with 32 percent of the patients who received medical therapy alone (P<0.001). Kaplan-Meier survival estimates at one year (based on an intention-to-treat analysis) were similar for the patients assigned to undergo transmyocardial revascularization and those assigned to receive medical therapy alone (84 percent and 89 percent, respectively; P=0.23). At one year, the patients in the transmyocardial-revascularization group had a significantly higher rate of survival free of cardiac events (54 percent, vs. 31 percent in the medical-therapy group; P<0.001), a significantly higher rate of freedom from treatment failure (73 percent vs. 47 percent, P<0.001), and a significantly higher rate of freedom from cardiac-related rehospitalization (61 percent vs. 33 percent, P<0.001). Exercise tolerance and quality-of-life scores were also significantly higher in the transmyocardial-revascularization group than in the medical-therapy group (exercise tolerance, 5.0 MET [metabolic equivalent] vs. 3.9 MET; P=0.05); quality-of-life score, 21 vs. 12; P=0.003). However, there were no differences in myocardial perfusion between the two groups, as assessed by thallium scanning. CONCLUSIONS: Patients with refractory angina who underwent transmyocardial revascularization and received continued medical therapy, as compared with similar patients who received medical therapy alone, had a significantly better outcome with respect to improvement in angina, survival free of cardiac events, freedom from treatment failure, and freedom from cardiac-related rehospitalization.


Subject(s)
Angina Pectoris/drug therapy , Angina Pectoris/surgery , Laser Therapy , Myocardial Revascularization/methods , Aged , Angina Pectoris/classification , Angina Pectoris/mortality , Cardiovascular Agents/therapeutic use , Combined Modality Therapy , Coronary Circulation , Disease-Free Survival , Exercise Tolerance , Female , Humans , Male , Middle Aged , Postoperative Complications/mortality , Prospective Studies , Quality of Life , Severity of Illness Index , Survival Analysis
10.
Semin Thorac Cardiovasc Surg ; 11(4 Suppl 1): 42-9, 1999 Oct.
Article in English | MEDLINE | ID: mdl-10660165

ABSTRACT

The early hemodynamic benefits of stentless aortic valves have been well documented. The issue of long-term functional integrity remains unanswered. We report the clinical results of a multicenter registry with prospective data on 621 patients monitored for 7.1 years. Patient data were collected and analyzed at St Jude Medical Inc, St Paul, Minnesota. In all, 66% of patients were male; the average age was 65.9 years +/-11.0 years, with 39% older than 70 years. Native aortic valves were bicuspid in 40.6%, 91.5% were calcified and 65.7% stenotic. Most valves implanted (83.1%) were sizes 25, 27, or 29 mm. Concomitant coronary bypass was performed in 42% of patients. Total follow-up time for the 621 patients was 1,944.5 valve years (mean 3.1 years per patient). At 5 years, 86.1% (n = 137) and at 6 years 80.4% (n = 51) were in New York Heart Association class I, and 78% had no or trivial atrial insufficiency. The average mean systolic gradient for all valves at 6 years was 4.0 mm Hg, and the peak gradient was 8.6 mm Hg. The effective orifice area varied from 1.4 cm2 (23-mm valve) to 2.7 cm2 (29-mm valve). The decrease in left ventricular mass index was significant and sustained. Actuarial survival at 6 years was 84.2%, and freedom from cardiac-related deaths was 90.1%. Freedom from valve-related deaths was 95.7%, and freedom from prosthetic endocarditis was 98.6%. There were no instances of primary tissue valve failure during follow-up, with 97.2% freedom from reoperation. The early hemodynamic benefits of the TSPV are well maintained during more than 6 years of follow-up, without evident valvular dysfunction. Longer follow-up time is required to validate durability, but there is increasing evidence for well-maintained structural and functional integrity.


Subject(s)
Heart Valve Prosthesis , Actuarial Analysis , Aged , Female , Hemodynamics , Humans , Male , Prospective Studies , Prosthesis Design , Time Factors , Treatment Outcome
11.
Semin Thorac Cardiovasc Surg ; 11(4 Suppl 1): 74-8, 1999 Oct.
Article in English | MEDLINE | ID: mdl-10660170

ABSTRACT

One of the contraindications for a stentless aortic valve is dilation of the aorta such that the sinotubular ridge is more than 2 mm larger than the annulus. Since May of 1994, 134 patients have had their aortic valve replaced with St Jude Toronto SPV valves; of these, 38 patients have required sinotubular ridge reduction. This was done by using one or more pleats in the aorta between the commisural posts. There were 20 patients with one pleat, 12 patients with two pleats, 5 patients with three pleats, and 1 patient with four pleats. In addition, three Toronto SPV valves were used in patients with significant calcification in the native coronary sinuses. All of the valves have had trace or no aortic insufficiency and have not developed aortic insufficiency in follow-up evaluation. Mean gradients remain low (<10 mm Hg). These valves have been much more versatile than originally expected and can be used in patients with mild to moderate aortic dilation and calcification.


Subject(s)
Aortic Valve/pathology , Aortic Valve/surgery , Bioprosthesis , Heart Valve Prosthesis , Aged , Aged, 80 and over , Dilatation, Pathologic , Female , Heart Valve Diseases/surgery , Humans , Male , Middle Aged , Prosthesis Design , Retrospective Studies , Suture Techniques
12.
Am J Cardiol ; 82(10): 1214-9, 1998 Nov 15.
Article in English | MEDLINE | ID: mdl-9832097

ABSTRACT

Stentless tissue valves may provide more favorable hemodynamics than conventional stented valves. Hemodynamic findings from a large multicenter trial have not been previously reported. The present report describes the hemodynamic findings from a multinational, multicenter study after implantation of the Toronto SPV valve. A total of 577 patients underwent aortic valve replacement with the Toronto SPV valve at 12 sites in 3 countries. Echocardiograms were recorded in the early postoperative period, 3 to 6 months after surgery, 1 year after surgery, and yearly thereafter, with follow-up to 3 years. Gradients decreased and effective orifice area increased in the months after surgery. One year after surgery, mean gradient for valve sizes 20 to 22, 23, 25, 27, and 29 mm was 7.3 +/- 4.4, 7.4 +/- 4.5, 6.1 +/- 3.3, 4.9 +/- 2.4, and 4.0 +/- 2.1 mm Hg, respectively; effective orifice area was 1.3 +/- 0.7, 1.5 +/- 0.5, 1.7 +/- 0.4, 2.0 +/- 0.4, and 2.4 +/- 0.6 cm2, respectively. There was a very low prevalence of significant aortic regurgitation at all time periods. There was significant left ventricular (LV) mass regression between the early and 3- to 6-month periods and between the 3- to 6-month and 1-year postoperative periods. The Toronto SPV valve has an excellent hemodynamic profile supported by significant regression of LV hypertrophy in the year after implantation. Data through 3 years demonstrates maintenance of low gradients and freedom from significant aortic regurgitation.


Subject(s)
Bioprosthesis , Heart Valve Prosthesis , Hemodynamics , Hypertrophy, Left Ventricular , Aged , Aortic Valve , Aortic Valve Insufficiency/diagnostic imaging , Aortic Valve Insufficiency/etiology , Cohort Studies , Female , Heart Valve Prosthesis Implantation , Humans , Hypertrophy, Left Ventricular/diagnostic imaging , Hypertrophy, Left Ventricular/surgery , Male , Middle Aged , Observer Variation , Postoperative Complications/diagnostic imaging , Postoperative Period , Prevalence , Ultrasonography
13.
Circulation ; 98(19 Suppl): II73-5; discussion II75-6, 1998 Nov 10.
Article in English | MEDLINE | ID: mdl-9852884

ABSTRACT

BACKGROUND: Previous reports of transmyocardial revascularization (TMR) indicate a significant mortality in patients with refractory, unstable angina. We hypothesized that TMR with a holmium laser would result in significant angina relief with acceptable mortality in this patient population. METHODS AND RESULTS: Patients were defined as unstable if they were unweanable from intravenous antianginal medications or were too unstable for a persantine thallium scan. Patients had a left ventricular ejection fraction (LVEF) of > 25% and were not amenable to CABG or PTCA. Before treatment, all patients had class IV angina. TMR was performed in 85 patients, with a mean of 35 +/- 11 transmural laser channels. Mean age was 63 +/- 10 years. Mean LVEF was 48 +/- 11%. Of these patients, 79% were men. Prior CABG and/or PTCA had been performed in 87% of patients, and 72% of patients had a history of prior MI. Operative mortality was 12% (10 of 85). There were 2 deaths between discharge and 3 months after surgery and 7 late deaths from 6 to 12 months after surgery. Twelve-month mortality was 22.4% (19 of 85). At 3 months, 86% of patients had class II angina or better. At 6 and 12 months, 77% and 75% of patients, respectively, had class II angina or better. Mean angina class at 6 and 12 months' follow-up was 1.5 +/- 1.1 and 1.6 +/- 1.3, respectively. CONCLUSIONS: In patients with refractory unstable angina, TMR with a holmium laser provided significant angina relief. Moreover, 30-day operative mortality and 12-month mortality were acceptable, especially given this subset of unstable patients with refractory angina.


Subject(s)
Angina, Unstable/surgery , Myocardial Revascularization/methods , Aged , Angina, Unstable/classification , Angina, Unstable/mortality , Female , Holmium , Humans , Intraoperative Complications/mortality , Laser Therapy/instrumentation , Lasers , Male , Middle Aged , Morbidity , Myocardial Revascularization/instrumentation , Postoperative Complications/epidemiology , Postoperative Complications/mortality , Prospective Studies
14.
Proc Natl Acad Sci U S A ; 95(15): 9009-13, 1998 Jul 21.
Article in English | MEDLINE | ID: mdl-9671795

ABSTRACT

In transgenic tobacco, pea Ferredoxin-1 (Fed-1) mRNA accumulates rapidly in response to photosynthesis even when the transgene is driven by a constitutive promoter. To investigate the role of photosynthesis on Fed-1 mRNA stability, we used the tetracycline repressible Top10 promoter system to specifically shut off transcription of the Fed-1 transgene. The Fed-1 mRNA has a half-life of approximately 2.4 hr in the light and a half-life of only 1.2 hr in the dark or in the presence of the photosynthetic electron transport inhibitor 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU). These data indicate that cessation of photosynthesis, either by darkness or DCMU results in a destabilization of the Fed-1 mRNA. Furthermore, the Fed-1 mRNA half-life is reduced immediately upon transfer to darkness, suggesting that Fed-1 mRNA destabilization is a primary response to photosynthesis rather than a secondary response to long-term dark adaptation. Finally, the two different methods for efficient tetracycline delivery reported here generally should be useful for half-life measurements of other mRNAs in whole plants.


Subject(s)
Ferredoxins/genetics , Photosynthesis , RNA, Messenger/metabolism , Diuron/pharmacology , Electron Transport , Half-Life , Histones/genetics , Photosynthesis/drug effects , Plants, Genetically Modified/genetics , Plants, Toxic , Promoter Regions, Genetic , Tetracycline/pharmacology , Nicotiana/genetics
15.
Plant Cell ; 10(3): 475-84, 1998 Mar.
Article in English | MEDLINE | ID: mdl-9501119

ABSTRACT

Light regulation of Fed-1 mRNA abundance in the leaves of green plants is primarily a post-transcriptional process. Previously, we have shown that the Fed-1 mRNA light response requires an open reading frame, indicating that the light regulation of the mRNA depends on its concurrent translation. We now show that light-induced increases in Fed-1 mRNA abundance are associated with increases in polyribosome association that require both a functional AUG and a normal Fed-1 translational start context. We also present evidence that light regulation of Fed-1 mRNA levels requires more than efficient translation per se. Substitution of the efficiently translated tobacco mosaic virus Omega 5' untranslated region resulted in a loss of Fed-1 light regulation. In addition, we identified a CAT T repeat element located near the 5' terminus of the Fed-1 5' untranslated region that is essential for light regulation. We introduced two different mutations in the CAT T repeat element, but only one of these substitutions blocked the normal light effect on polyribosome association, whereas both altered dark-induced Fed-1 mRNA disappearance. The element may thus be important for Fed-1 mRNA stability rather than polyribosome loading. We propose a model in which Fed-1 mRNA is relatively stable when it is associated with polyribosomes in illuminated plants but in darkness is not polyribosome associated and is thus rapidly degraded by a process involving the CAT T repeat element.


Subject(s)
Ferredoxins/genetics , Gene Expression Regulation, Plant/radiation effects , Light , Nicotiana/genetics , Plants, Toxic , Polyribosomes/metabolism , RNA, Messenger/metabolism , Codon , Enhancer Elements, Genetic , Mutagenesis, Site-Directed , Plants, Genetically Modified , Protein Biosynthesis , Regulatory Sequences, Nucleic Acid
17.
Plant Cell ; 9(12): 2291-300, 1997 Dec.
Article in English | MEDLINE | ID: mdl-9437868

ABSTRACT

In transgenic tobacco plants containing a pea ferredoxin transcribed region (Fed-1) driven by the cauliflower mosaic virus 35S promoter (P35S), light acts at a post-transcriptional level to control the abundance of Fed-1 mRNA in green leaves. To determine whether the light signal for this response involves photosynthesis, we treated transgenic seedlings with or without 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU), an inhibitor of photosynthetic electron transport. DCMU prevented the normal light response by blocking reaccumulation of Fed-1 transcripts when dark-adapted green plants were returned to the light. In contrast, reaccumulation of light-harvesting complex B (Lhcb) transcripts was unaffected by DCMU treatment. Because Fed-1 light regulation requires translation, we also examined polyribosome profiles. We found that Fed-1 transcripts accumulated on polyribosomes in the light but were found primarily in non-polyribosomal fractions in dark-adapted plants or in illuminated plants exposed to lower than normal light intensity or treated with DCMU. Surprisingly, although Lhcb mRNA abundance was not affected by DCMU, its polyribosomal loading pattern was altered in much the same way as was that of Fed-1 mRNA. In contrast, DCMU had no effect on either the abundance or the polyribosome profiles of endogenous histone H1 or transgenic P35S::CAT transcripts. Thus, our results are consistent with the hypothesis that a process coupled to photosynthesis affects the polyribosome loading of a subset of cytoplasmic mRNAs.


Subject(s)
Ferredoxins/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA, Plant/genetics , RNA, Plant/metabolism , Diuron/pharmacology , Light , Pisum sativum/genetics , Photosynthesis , Plants, Genetically Modified , Plants, Toxic , Polyribosomes/drug effects , Polyribosomes/metabolism , Polyribosomes/radiation effects , RNA Processing, Post-Transcriptional/drug effects , RNA Processing, Post-Transcriptional/radiation effects , Nicotiana/genetics , Nicotiana/metabolism , Nicotiana/radiation effects
18.
EMBO J ; 13(15): 3648-58, 1994 Aug 01.
Article in English | MEDLINE | ID: mdl-8062839

ABSTRACT

We have identified a protein in Chlamydomonas reinhardtii cell extracts that specifically binds the single-stranded (ss) Chlamydomonas G-strand telomere sequence (TTTTAGGG)n. This protein, called G-strand binding protein (GBP), binds DNA with two or more ss TTTTAGGG repeats. A single polypeptide (M(r) 34 kDa) in Chlamydomonas extracts binds (TTTTAGGG)n, and a cDNA encoding this G-strand binding protein was identified by its expression of a G-strand binding activity. The cDNA (GBP1) sequence predicts a protein product (Gbp1p) that includes two domains with extensive homology to RNA recognition motifs (RRMs) and a region rich in glycine, alanine and arginine. Antibody raised against a peptide within Gbp1p reacted with both the 34 kDa polypeptide and bound G-strand DNA-protein complexes in gel retardation assays, indicating that GBP1 encodes GBP. Unlike vertebrate heteronuclear ribonucleoproteins, GBP does not bind the cognate telomere RNA sequence UUUUAGGG in gel retardation, North-Western or competition assays. Thus, GBP is a new type of candidate telomere binding protein that binds, in vitro, to ss G-strand telomere DNA, the primer for telomerase, and has domains that have homology to RNA binding domains in other proteins.


Subject(s)
Chlamydomonas reinhardtii/metabolism , DNA-Binding Proteins/metabolism , GTP-Binding Proteins , Genes, Protozoan/genetics , Protozoan Proteins/metabolism , Amino Acid Sequence , Animals , Base Sequence , Chlamydomonas reinhardtii/genetics , Cloning, Molecular , Consensus Sequence , DNA, Complementary , DNA, Protozoan/genetics , DNA, Protozoan/metabolism , DNA, Single-Stranded/genetics , DNA, Single-Stranded/metabolism , DNA-Binding Proteins/genetics , DNA-Binding Proteins/isolation & purification , Molecular Sequence Data , Plant Proteins , Protozoan Proteins/genetics , Protozoan Proteins/isolation & purification , RNA, Messenger/analysis , RNA, Messenger/metabolism , RNA, Protozoan/analysis , RNA, Protozoan/metabolism , Repetitive Sequences, Nucleic Acid/genetics , Sequence Analysis, DNA , Sequence Homology, Amino Acid , Telomere/metabolism
19.
Ann Surg ; 219(6): 707-13; discussion 713-4, 1994 Jun.
Article in English | MEDLINE | ID: mdl-8203981

ABSTRACT

OBJECTIVE: This study determined predictors of operative survival and improved long-term outcomes in patients undergoing ventricular aneurysmectomy. SUMMARY BACKGROUND DATA: Since the first successful repair of ventricular aneurysm in 1958, refined technique and improvement in perioperative care have been introduced to lower morbidity and mortality. METHODS: The authors reviewed their institutional experience from 1968 through 1993 in treating 523 patients who underwent ventricular aneurysmectomy. RESULTS: Overall operative mortality was 8% and overall median survival was 128 months. Contractility grade, age, and year of operation were predictors of operative mortality and of improved long-term survival. Type of aneurysm repair was not a strong predictor of operative mortality or improved long-term survival. CONCLUSIONS: Ventricular aneurysmectomy can be performed safely using one of a number of established techniques, although operative mortality and long-term survival may not depend on the techniques used.


Subject(s)
Heart Aneurysm/surgery , Heart Ventricles/surgery , Adult , Aged , Aged, 80 and over , Cardiac Surgical Procedures/methods , Female , Heart Aneurysm/mortality , Heart Aneurysm/physiopathology , Heart Ventricles/physiopathology , Humans , Logistic Models , Male , Middle Aged , Myocardial Contraction , Postoperative Complications/epidemiology , Survival Rate , Time Factors , Treatment Outcome
20.
Ann Thorac Surg ; 53(5): 776-8; discussion 779, 1992 May.
Article in English | MEDLINE | ID: mdl-1570969

ABSTRACT

Current videoendoscopic technology and percutaneous techniques of exposure and dissection have been successfully applied to abdominal surgery with favorable results. Application of this technology to our practice of thoracoscopy is the basis of this report. Videothoracoscopy has been performed in 39 patients for the following indications: chronic pleural effusion, interstitial lung disease, mediastinal lymphadenopathy in lung cancer, persistent air leak after decortication, mediastinal mass, recurrent spontaneous pneumothorax, hydropneumothorax with persistent air leak, and pleural-based mass. The technique we employ includes lateral decubitus positioning and double-lumen endotracheal intubation with ipsilateral lung collapse. The videoscope, retractors, and instruments are introduced through separate 10-mm incisions. Percutaneous manipulation of instruments and the videoscope is guided by images produced on television screens without dissection, and if resection is performed, the incision is enlarged to allow specimen retrieval. Procedures performed using this technique include pleural biopsy, partial pleurectomy, lysis of adhesions, lung biopsies, staging lymph node biopsy, lung nodule biopsy, pleural-based mass resection, and mediastinal mass biopsy and resection. This videoendoscopic technique greatly improves visualization of thoracic anatomy, facilitating thoracoscopy and enhancing exploration of the chest. It is preferred over conventional thoracoscopy and, in some patients, reduces the magnitude of operation by avoiding thoracotomy.


Subject(s)
Thoracoscopy/methods , Adult , Aged , Chronic Disease , Female , Humans , Lung Diseases/pathology , Lung Neoplasms/pathology , Male , Mediastinal Neoplasms/pathology , Middle Aged , Neoplasm Staging , Pleural Effusion/pathology , Pleurisy/pathology , Video Recording/methods
SELECTION OF CITATIONS
SEARCH DETAIL
...