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1.
J Am Coll Cardiol ; 71(24): 2717-2726, 2018 06 19.
Article in English | MEDLINE | ID: mdl-29903344

ABSTRACT

BACKGROUND: The burden oral anticoagulation is a limitation of mechanical valve prostheses. OBJECTIVES: The aim of this study was to test whether patients could be safely managed with dual-antiplatelet therapy (DAPT) (aspirin 325 mg and clopidogrel 75 mg) or lower warfarin after On-X mechanical aortic valve replacement (mAVR). METHODS: PROACT (Prospective Randomized On-X Anticoagulation Trial) (n = 576) is a multicenter (41 sites) noninferiority trial. From June 2006 through February 2014, 201 patients ≥18 years of age without thromboembolic risk factors undergoing mAVR were randomized to receive DAPT (n = 99) or standard warfarin plus aspirin (n = 102) 3 months after mAVR (low-risk arm). From June 2006 through October 2009, 375 patients with 1 or more thromboembolic risk factors were also randomized to lower intensity warfarin plus aspirin (international normalized ratio 1.5 to 2.0; n = 185) or standard warfarin plus aspirin (international normalized ratio 2.0 to 3.0; n = 190) 3 months after mAVR (high-risk arm). RESULTS: The low-risk arm was terminated for excess cerebral thromboembolic events (3.12% per patient-year vs. 0.29% per patient-year, p = 0.02) in the DAPT group at up to 8.8-year follow-up (631.6 patient-years), with no differences in bleeding or all-cause mortality. High-risk arm patients experienced significantly lower major (1.59% per patient-year vs. 3.94% per patient-year, p = 0.002) and minor (1.27% per patient-year vs. 3.49% per patient-year, p = 0.002) bleeding up to 8.7-year follow-up (2,035.2 patient-years), with no differences in thromboembolism (0.42% per patient-year vs. 0.09% per patient-year, p = 0.20) and all-cause mortality. CONCLUSIONS: DAPT was associated with higher rates of thromboembolism and valve thrombosis compared with control in the low-risk arm. International normalized ratios were safely maintained at 1.5 to 2.0 in high-risk patients, without differences in mortality or thromboembolic complications. (Randomized On-X Anticoagulation Trial [PROACT]; NCT00291525).


Subject(s)
Anticoagulants/administration & dosage , Aortic Valve/surgery , Heart Valve Prosthesis Implantation , Platelet Aggregation Inhibitors/administration & dosage , Postoperative Complications/prevention & control , Thromboembolism/prevention & control , Adult , Aged , Aspirin/administration & dosage , Clopidogrel/administration & dosage , Female , Humans , Male , Middle Aged , Prospective Studies , Warfarin/administration & dosage
2.
Sci Total Environ ; 579: 124-132, 2017 Feb 01.
Article in English | MEDLINE | ID: mdl-27866745

ABSTRACT

Speleothem-like deposits that develop underground in urban areas are an archive of the environmental impact of anthropic activities that has been little studied so far. In this paper, the sulfate content in shallow groundwater from northern Paris (France) is compared with the sulfur content in two 300-year-old urban carbonate deposits that grew in a historical underground aqueduct. The present-day waters of the aqueduct have very high sulfur and calcium contents, suggesting pollution from gypsum dissolution. However, geological gypsum levels are located below the water table. Sulfur content was measured by micro-X-ray fluorescence in these very S-rich carbonate deposits (0.5 to 1% of S). A twofold S increase during the second half of the 1800s was found in both samples. These dates correspond to two major periods of urbanization above the site. We discus three possible S sources: anthropic sources (industries, fertilizers…), volcanic eruptions and input within the water through gypsum brought for urbanization above the studied site (backfill with quarry waste) since the middle of the 19th century. For the younger second half of the studied section, S input from gypsum brought during urbanization was confirmed by the study of isotopic sulfur composition (δ34S=+15.2‰ at the top). For the oldest part, several sulfur peaks could be related to early industrial activity in Paris, that caused high local air pollution, as reported in historical archives but also to historical gypsum extraction. This study provides information on the origin and timing of the very high SO42- levels measured nowadays within the shallow groundwater, thus demonstrating the interest in using carbonate deposits in urban areas as a proxy for the history of urbanization or human activities and their impact on water bodies.


Subject(s)
Environmental Monitoring , Groundwater/chemistry , Sulfur/analysis , Water Pollutants, Chemical/analysis , France , Paris , Urbanization
3.
Ann Thorac Surg ; 78(5): 1659-64, 2004 Nov.
Article in English | MEDLINE | ID: mdl-15511452

ABSTRACT

BACKGROUND: Postcardiotomy sternal wound complications remain challenging. The prevailing approach for deep sternal wound infection of debridement and flap coverage without osseous closure makes subsequent reoperation difficult. METHODS: An analysis of all patients undergoing cardiac surgery at a single institution between 1986 and 2001 was conducted. Prospective data collection and chart review were used to compare different treatment strategies for sternal complications. RESULTS: Of 5337 patients, 122 had sternal wound complications (2.2%) comprising 15 (0.3%) uninfected dehiscences (El Oakley class 1), 45 (0.8%) superficial infections (El Oakley class 2A), and 62 (1.1%) deep sternal wound infections (El Oakley class 2B). Thirty-two patients with deep sternal infection were treated by debridement, rewiring, and delayed primary closure. There were initial treatment failures in 6 patients (18.8%) and ultimate failures in 2 patients (6.3%), both of whom died. One of these patients had previously received external beam radiation after a radical mastectomy for breast cancer. Median length of stay was 32 days and median time to wound healing was 85 days. Twenty-five patients were managed by muscle flap coverage without sternal reclosure. There were 6 initial treatment failures (24%) but no ultimate failures or deaths (p = NS). Median length of stay was 31 days and median infection time was 161 days. CONCLUSIONS: In patients with postcardiotomy deep sternal wound infection without previous chest radiation, debridement, rewiring, and delayed skin closure is effective. It offers a shorter healing time and probably makes late cardiac reoperation safer. We propose an algorithm for the management of poststernotomy complications.


Subject(s)
Cardiac Surgical Procedures , Sternum/surgery , Surgical Wound Dehiscence/surgery , Surgical Wound Infection/surgery , Algorithms , Antibiotic Prophylaxis , Bone Wires , Debridement , Female , Hospital Mortality , Humans , Length of Stay/statistics & numerical data , Male , Prospective Studies , Radiation Injuries/complications , Radiotherapy/adverse effects , Registries , Reoperation , Risk Factors , Surgical Flaps , Surgical Wound Dehiscence/therapy , Surgical Wound Infection/therapy , Treatment Outcome , Wound Healing
4.
Chest ; 122(1): 21-30, 2002 Jul.
Article in English | MEDLINE | ID: mdl-12114334

ABSTRACT

OBJECTIVE: To compare baseline preoperative and 6-month postoperative functional health status and quality of life in patients undergoing lung cancer resection. METHODS: Lung cancer surgery patients from three hospitals were administered the Short-Form 36 Health Survey (SF-36) and the Ferrans and Powers' quality-of-life index (QLI) before surgery and 6 months after surgery. Preoperative, intraoperative, hospital stay, and 6-month postoperative clinical data were collected. All p values

Subject(s)
Health Status , Lung Neoplasms/surgery , Quality of Life , Adult , Aged , Aged, 80 and over , Case-Control Studies , Combined Modality Therapy , Female , Humans , Lung Neoplasms/mortality , Lung Neoplasms/psychology , Male , Middle Aged , Pain Measurement , Postoperative Complications , Postoperative Period , Thoracic Surgery, Video-Assisted , Treatment Outcome
5.
Ann Thorac Surg ; 72(6): 1855-9; discussion 1859-60, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11789760

ABSTRACT

BACKGROUND: Our objective was to define the prevalence, patterns, and predisposing characteristics for hospital readmission after pulmonary resection. METHODS: Five years of pulmonary resections, excluding lung biopsies, were analyzed from a prospective, computerized database. Readmission was defined as inpatient or emergency department admission within 90 days of operation. Search of 1,173,912 admissions to the Providence Health System in Oregon identified readmissions. Readmission analysis excluded operative deaths. RESULTS: A total of 374 patients underwent pulmonary resections, of whom 8 died (2.1%). Of 366 patients discharged, 69 (18.9%) were readmitted a total of 113 times: 42 had only one readmission, 16 had two readmissions, 7 had three readmissions, 2 had four readmissions, and 2 had five readmissions. Slightly more than half (51%) were readmitted as inpatients. Causes of the 113 readmissions included pulmonary (27%), postoperative infection (14%), cardiac (7%), and other (16%). Mean time to readmission was 32.5 +/- 24.6 days. Inpatient readmission mean length of stay was 4.9 +/- 3.4 days. Readmission to hospitals other than the hospital of the operation was as follows: first readmission, 15.9%; second readmission, 14.8%; third readmission, 36.3%; fourth readmission, 25%; fifth readmission, 0%. Analysis revealed only pneumonectomy as a risk for readmission. Twelve of 33 (36%) pneumonectomies were readmitted (p = 0.005). Of the 297 patients discharged after pulmonary resection and not requiring readmission, 12 (4%) died over the study interval, whereas 8 of 69 patients (11.6%) requiring readmission died. CONCLUSIONS: Readmission after pulmonary resection is frequent and multiple readmissions are common. Causes are predominately pulmonary diagnoses and infections related to the operation. Pneumonectomy is a risk for readmission. An important portion of readmissions occurs outside the hospital of operation. The population requiring readmission after successfully undergoing pulmonary resection is at increased risk of subsequent mortality.


Subject(s)
Patient Readmission/statistics & numerical data , Pneumonectomy/standards , Postoperative Complications/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Causality , Female , Hospital Records/statistics & numerical data , Humans , Length of Stay/statistics & numerical data , Male , Managed Care Programs/statistics & numerical data , Middle Aged , Oregon/epidemiology , Postoperative Complications/surgery , Risk
6.
Chest ; 118(6): 1621-5, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11115449

ABSTRACT

PURPOSE: To evaluate the outcomes of patients surgically treated for their second primary lung cancer. METHOD: In a computerized surgical registry of > 800 consecutive patients treated for primary pulmonary carcinoma since 1980, 37 patients presented with a second lung cancer. These patients were analyzed regarding their original treatment, preoperative evaluation, operative procedures, and long-term follow-up. RESULTS: Three fifths of the patients were female, and 57% were > or = 65 years old at the time of their second operation. One patient originally had two synchronous tumors; another patient had three metachronous neoplasms. The interval between surgeries ranged from 5 to 239 months. In 31 patients, treatment for their original tumor was surgical resection alone. Lobectomy was the most common operation for the original tumor, and 78% were stage I. When the second tumor was diagnosed, 25 patients (68%) were asymptomatic. Eight patients (22%) were current smokers, and 29 patients (78%) were former smokers. The most common operation for the second tumor was a lobectomy. Surgical mortality was 5.4%. Nineteen patients (51%) survived 2 years, and 9 patients (24%) survived > or = 5 years. Eleven patients (30%) were still alive at last follow-up, 3 to 198 months postoperatively, and only 13 patients (34%) had died of their cancer. CONCLUSION: Surgical treatment of second primary pulmonary neoplasms can be performed in selected patients with acceptable long-term survival.


Subject(s)
Lung Neoplasms/surgery , Neoplasms, Second Primary/surgery , Aged , Female , Humans , Lung Neoplasms/diagnosis , Lung Neoplasms/mortality , Male , Neoplasms, Second Primary/diagnosis , Neoplasms, Second Primary/mortality
7.
Ann Thorac Surg ; 70(2): 373-9, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10969647

ABSTRACT

BACKGROUND: We sought to determine if median sternotomy (MS) is an equivalent incision to thoracotomy (TH) in the treatment of primary pulmonary carcinoma. METHODS: We followed 801 patients undergoing 815 operations for primary lung carcinoma in a computer registry; 447 had MS, 368 had TH. RESULTS: Both groups were similar in preoperative risk assessment. Complete staging lymph node dissections were performed in 42% of MS patients and 17% of TH patients. Operative mortality (3.8% for MS, 3.3% for TH) and postoperative complications were similar. MS patients had a shorter postoperative hospital stay (7.5 days vs. 8.2 days). One hundred thirty-nine underwent pneumonectomy. Operative mortality was 12.5% for MS and 10.4% for TS (p = NS). Five hundred eighty-one underwent lobectomy with an operative mortality of 2.1% for MS and 2.0% for TH. Mean length of stay for MS lobectomy was 7.5 days compared with 8.5 days for TH (p = 0.06). Follow-up was 89% through 1998, comprising 1,339 MS and 1,463 TH patient-years. Survival for stage I at 5 and 10 years, respectively, was 51% and 34% for MS vs 54% and 32% for TH (p = NS). Survival for other stages was also similar. CONCLUSIONS: Median sternotomy provides more complete staging, shorter postoperative hospitalization, and better patient acceptance with equivalent operative and long-term survival when compared with thoracotomy. Concerns regarding increased wound infections in MS patients appear unfounded.


Subject(s)
Adenocarcinoma/surgery , Carcinoma, Large Cell/surgery , Carcinoma, Squamous Cell/surgery , Lung Neoplasms/surgery , Sternum/surgery , Thoracotomy , Female , Humans , Length of Stay , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Lymph Node Excision , Male , Middle Aged , Neoplasm Staging , Pain, Postoperative/etiology , Risk Factors , Treatment Outcome
8.
Trends Cell Biol ; 9(10): 417, 1999 Oct.
Article in English | MEDLINE | ID: mdl-10481181
9.
Heart Surg Forum ; 2(1): 41-6, 1999.
Article in English | MEDLINE | ID: mdl-11276459

ABSTRACT

BACKGROUND: Minimally invasive direct coronary artery bypass (MIDCAB) has been criticized as compromising anastomotic patency. Epicardial mechanical stabilization devices purportedly facilitate left internal mammary artery (LIMA) anastomosis, thereby enhancing patency and outcome. METHODS: From June 1996 through January 1999, 39 patients underwent MIDCAB via a small left anterior thoracotomy for revascularization of the left anterior descending coronary artery (LAD) without cardiopulmonary bypass (CPB). Immediate postoperative coronary angiography was performed on 38 of the patients. RESULTS: Group 1 consisted of 11 patients who were operated upon without epicardial stabilization. Mean age was 64 years. Two had undergone previous coronary artery bypass (CAB). Predicted mortality was 4.3%. Angiographic anastomotic patency was 60%. Revisions on CPB in three cases increased LIMA patency to 90%. There was one intra-operative death. Average length of stay (LOS) was 5.4 days. Group 2 consisted of 28 patients operated on with mechanical epicardial stabilization. Predicted risk of mortality was 4.4%. Mean age was 66 years. Twelve had undergone previous CAB. Anastomotic patency at angiography was 97.4%. There were no intra-operative deaths and mean LOS was 3.0 days. CONCLUSIONS: We conclude that mechanical epicardial stabilization has transformed the MIDCAB operation into one that offers excellent early patency and clinical outcomes. This operation is of particular value for revascularization of the anterior coronary circulation in patients with previous CAB; clinical results are significantly better than predicted for standard redo-CAB.


Subject(s)
Coronary Angiography , Coronary Artery Bypass , Immobilization , Internal Mammary-Coronary Artery Anastomosis , Minimally Invasive Surgical Procedures , Postoperative Complications/diagnostic imaging , Aged , Female , Heart-Lung Machine , Hospital Mortality , Humans , Male , Middle Aged , Postoperative Complications/mortality , Reoperation , Survival Rate , Treatment Outcome
10.
Curr Biol ; 8(1): 46-55, 1998 Jan 01.
Article in English | MEDLINE | ID: mdl-9427625

ABSTRACT

BACKGROUND: Ksr (kinase supressor of Ras) was identified as a regulator of the Ras-MAP kinase (mitogen-activated protein kinase) pathway by genetic screens in Drosophila and Caenorhabditis elegans. Ksr is a kinase with similarities to the three conserved regions of Raf kinases, especially within the kinase domain. To investigate whether these structural similarities correlated with common functional properties, we examined the ability of mKsr-1, the murine homolog of Ksr, to interact with components of the vertebrate MAP kinase pathway. RESULTS: In the yeast two-hybrid interaction assay, mKsr-1 did not bind to either Ras, B-Raf or Raf-1, but interacted strongly with both MEK-1 and MEK-2, activators of MAP kinase. The Ksr-MEK interaction was confirmed by co-immunoprecipitation experiments. Ectopically expressed mKsr-1 co-precipitated with endogenous MEK-1 in COS-1 cells, and endogenous Ksr and MEK co-precipitated from PC12 cells. Phosphorylation of MEK by mKsr-1 was not detected, however. In contrast, the MEK subpopulation complexed with mKsr-1 in COS-1 cells or PC12 cells did not display kinase activity. This ability of Ksr to block MEK in an inactive form correlated with a biological response: mKsr-1 did not transform NIH3T3 cells, and, furthermore, mKsr-1 reduced Ras-induced transformation. Similarly, mKsr-1 inhibited the proliferation of embryonic neuroretina cells induced by Ras and B-Raf but not that induced by MEK. CONCLUSIONS: Our results suggest a novel mechanism for Ksr in regulating the MAP kinase pathway, at least in part through an ability to interact with MEK.


Subject(s)
Cell Transformation, Neoplastic/drug effects , Mitogen-Activated Protein Kinase Kinases , Protein Kinases/metabolism , Protein Serine-Threonine Kinases/metabolism , Protein-Tyrosine Kinases/metabolism , Signal Transduction , ras Proteins/antagonists & inhibitors , 3T3 Cells , Animals , COS Cells , Cell Division/drug effects , Chick Embryo , Epidermal Growth Factor/pharmacology , MAP Kinase Kinase 1 , MAP Kinase Kinase 2 , Mice , Nerve Growth Factors/pharmacology , PC12 Cells , Proto-Oncogene Proteins c-raf/metabolism , Rats , Retina/drug effects
11.
Oncogene ; 15(4): 373-83, 1997 Jul 24.
Article in English | MEDLINE | ID: mdl-9242373

ABSTRACT

SOS, the guanine nucleotide exchange factor for Ras, becomes phosphorylated on serine and threonine residues following stimulation of cells with growth factors. These phosphorylations may play a role in negative feedback of Ras stimulation and have been shown to be mediated in part by the MAP kinases Erk-1 and Erk-2. Here we show that in addition to MAP kinase, a major mitogen activated kinase for SOS is p90 Rsk-2, a downstream target of MAP kinase. p90 Rsk-2 phosphorylates SOS in an in gel assay and also in solution in vitro. The ability of p90 Rsk-2 to phosphorylate SOS increases greatly following EGF treatment of PC12 cells and is blocked by expression of N17 Ras or treatment with the MEK inhibitor PD98059. Phosphopeptide mapping revealed that the sites phosphorylated by p90 Rsk-2 in vitro were also phosphorylated in intact cells in response to EGF treatment. Several major sites of in vivo phosphorylation correlated with p90 Rsk-2 phosphorylation sites rather than MAP kinase sites. It is therefore likely that p90 Rsk-2 plays an important role in the down regulation of the Ras activation pathway through SOS.


Subject(s)
Calcium-Calmodulin-Dependent Protein Kinases/physiology , Epidermal Growth Factor/pharmacology , Membrane Proteins/metabolism , Amino Acid Sequence , Animals , Chromatography, Ion Exchange , Molecular Sequence Data , Molecular Weight , PC12 Cells , Phosphorylation , Protein Serine-Threonine Kinases/physiology , Rats , Son of Sevenless Proteins , ras Proteins/physiology
12.
J Biol Chem ; 270(37): 21524-31, 1995 Sep 15.
Article in English | MEDLINE | ID: mdl-7665564

ABSTRACT

The LAMMER subfamily of kinases has been conserved throughout evolution, and its members are thought to play important roles in the regulation of cellular growth and differentiation programs. STY is a murine LAMMER kinase which has been implicated in the control of PC12 cell differentiation. Multiple transcripts are derived from the Sty gene, and their relative abundance is developmentally regulated. Alternative splicing of the primary Sty transcript generates mRNAs encoding full-length catalytically active (STY) and truncated, kinase-deficient polypeptides. Both STY and its truncated isoform, STYT, are localized in the nucleus and are capable of heterodimerizing. We also demonstrate that STY functions as a dual specificity kinase in mammalian cells.


Subject(s)
Alternative Splicing , Cell Nucleus/enzymology , Protein Kinases/biosynthesis , Protein Serine-Threonine Kinases , Protein-Tyrosine Kinases/biosynthesis , RNA, Messenger/biosynthesis , Amino Acid Sequence , Animals , Base Sequence , Cell Line , Chlorocebus aethiops , Cloning, Molecular , Exons , Humans , Mice , Molecular Sequence Data , PC12 Cells , Polymerase Chain Reaction , Rats , Recombinant Fusion Proteins/biosynthesis , Sequence Homology, Amino Acid , Transcription, Genetic , Transfection
13.
Cancer Metastasis Rev ; 13(1): 1-7, 1994 Mar.
Article in English | MEDLINE | ID: mdl-8143341

ABSTRACT

Phosphorylation/dephosphorylation reactions are one of the dynamic mechanisms through which cells modulate protein activity in response to environmental stimuli. The eukaryotic molecules which are responsible for the phosphorylation of serine, threonine and tyrosine residues appear to have co-ordinately evolved from simple prokaryotic enzymes which primarily respond to nutritional cues. In multicellular eukaryotes the complexity of data transfer greatly exceeds that of simple bacteria. The eukaryotic cell needs to exchange information with neighbouring and distant sister cells. Positional, nutritional and hormonal data are transmitted from the extracellular milieu across the plasma membrane and into the cytoplasm. In certain cases the signal must pass into the nucleus or other subcellular organelles where it is decoded and the proper cellular response initiated. All of these events have been shown to have a protein kinase component and it seems likely that in mammalian cells over 1,000 different kinase molecules have evolved to form the requisite signal transducing networks. In this review we describe a previously unappreciated family of protein kinases, the dual specificity or DSK kinases, which play important roles in the regulation of normal cellular growth and differentiation.


Subject(s)
Cell Transformation, Neoplastic , Protein Kinases/metabolism , Signal Transduction , Animals , Cell Cycle , Cell Line , Homeostasis , Humans , Phosphorylation , Protein Biosynthesis , Substrate Specificity
14.
Ann Thorac Surg ; 54(1): 56-61, 1992 Jul.
Article in English | MEDLINE | ID: mdl-1610255

ABSTRACT

Retrograde cardioplegia administered through the coronary sinus has several documented advantages over antegrade cardioplegia but has been thought to provide inadequate right ventricular myocardial protection. We prospectively compared the effects of retrograde and antegrade cardioplegia on right ventricular performance in patients undergoing myocardial revascularization. Two groups of similar age, extent of disease, and preoperative left ventricular ejection fraction received retrograde (n = 16) or antegrade (n = 14) crystalloid cardioplegia. A right ventricular rapid-response thermistor catheter, previously developed and validated in our institution, was used to measure right atrial pressure, pulmonary artery pressure, right ventricular ejection fraction, end-diastolic volume index, and stroke volume index before bypass (baseline) and at several intervals after bypass. There were no differences in cross-clamp time, heart rate, cardiac enzymes, inotrope requirements, or arrhythmias between the two groups. Right ventricular parameters were equivalent in both groups at all time intervals except 30 minutes after bypass, at which time right ventricular end-diastolic volume index was lower (80 +/- 6 versus 93 +/- 6 mL/m2; p less than 0.05) and right ventricular stroke volume index was higher (35 +/- 3 versus 29 +/- 2 mL/m2, p less than 0.05) in the retrograde group compared with the antegrade group, indicating better right ventricular function with retrograde cardioplegia early after bypass. In both groups, right ventricular end-diastolic volume index was higher than baseline (p less than 0.05) during the first 4 hours after bypass. No other important differences were found.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Heart Arrest, Induced/methods , Ventricular Function, Right/physiology , Aged , Blood Pressure/physiology , Cardiac Catheterization , Female , Heart Arrest, Induced/adverse effects , Humans , Male , Middle Aged , Prospective Studies , Pulmonary Artery/physiology , Stroke Volume/physiology , Thermodilution/methods
15.
Mol Cell Biol ; 12(6): 2681-9, 1992 Jun.
Article in English | MEDLINE | ID: mdl-1375325

ABSTRACT

A novel protein kinase, the Esk kinase, has been isolated from an embryonal carcinoma (EC) cell line by using an expression cloning strategy. Sequence analysis of two independent cDNA clones (2.97 and 2.85 kb) suggested the presence of two Esk isoforms in EC cells. The esk-1 cDNA sequence predicted an 857-amino-acid protein kinase with a putative membrane-spanning domain, while the esk-2 cDNA predicted an 831-amino-acid kinase which lacked this domain. In adult mouse cells, esk mRNA levels were highest in tissues possessing a high proliferation rate or a sizeable stem cell compartment, suggesting that the Esk kinase may play some role in the control of cell proliferation or differentiation. As anticipated from the screening procedure, bacterial expression of the Esk kinase reacted with antiphosphotyrosine antibodies on immunoblots. Furthermore, in in vitro kinase assays, the Esk kinase was shown to phosphorylate both itself and the exogenous substrate myelin basic protein on serine, threonine, and tyrosine residues, confirming that the Esk kinase is a novel member of the serine/threonine/tyrosine family of protein kinases.


Subject(s)
Protein Kinases/genetics , Amino Acid Sequence , Animals , Base Sequence , Cell Compartmentation , Cell Membrane/enzymology , Cloning, Molecular , Cytoplasm/enzymology , DNA/genetics , Gene Expression , In Vitro Techniques , Mice , Molecular Sequence Data , Phosphoproteins/genetics , Phosphoserine/metabolism , Phosphothreonine/metabolism , Phosphotyrosine , Protein Kinases/metabolism , RNA, Messenger/genetics , Sequence Alignment , Substrate Specificity , Tumor Cells, Cultured , Tyrosine/analogs & derivatives , Tyrosine/metabolism
16.
Ann Thorac Surg ; 51(6): 893-9; discussion 900, 1991 Jun.
Article in English | MEDLINE | ID: mdl-2039317

ABSTRACT

Mortality after Fontan operation is related to risk factors like ventricular hypertrophy, pulmonary artery deformity, and young age (infancy). Preliminary procedures may improve Fontan results. The hemi-Fontan operation includes atriopulmonary anastomosis and correction of all anatomical risk factors, but an atriopulmonary patch directs superior vena caval flow into both pulmonary arteries and inferior vena caval flow into the ventricle, thus maintaining cardiac output (modified Glenn physiology). We performed 17 hemi-Fontan procedures in 16 patients, 14 primarily (median age, 9 months) and 3 for takedown of a Fontan operation. The 14 primary operations were for hypoplastic left heart syndrome (5), pulmonary atresia with intact ventricular septum (4), and other (5). All patients had multiple risk factors. Extubation was at 18 hours (median), chest tube removal was at 3 days, and hospital discharge was at 8 days postoperatively. Important complications included subglottic stenosis, transient diaphragmatic paralysis, pulmonary artery stenosis and thrombosis requiring reoperation, and transient ventricular fibrillation. One patient required hemi-Fontan takedown, and this patient later (3 months postoperatively) became the only death. Fontan take-downs have had a high mortality rate. In 3 patients who tolerated Fontan operation poorly, converting Fontan to hemi-Fontan abruptly reversed the downhill course. For these patients, the operation was life-saving. Hemi-Fontan operation is safe and well-tolerated, even in infants, provides the advantages of modified Glenn physiology before Fontan operation, and may be especially useful for Fontan takedown after failed Fontan.


Subject(s)
Cardiac Surgical Procedures/methods , Heart Ventricles/abnormalities , Cardiac Surgical Procedures/mortality , Child, Preschool , Heart Defects, Congenital/surgery , Heart Ventricles/surgery , Humans , Infant , Postoperative Complications , Reoperation
17.
Mol Cell Biol ; 11(1): 568-72, 1991 Jan.
Article in English | MEDLINE | ID: mdl-1986248

ABSTRACT

We have cloned a novel kinase (STY) from an embryonal carcinoma cell line. Sequence analysis of the STY cDNA reveals that it shares sequence homology with serine/threonine-type kinases and yet the bacterial expression product of the STY cDNA appears to have serine-, threonine-, and tyrosine-phosphorylating activities. The predicted STY protein is highly basic and contains a putative nuclear localization signal. During differentiation, two new mRNAs were detected in addition to the embryonic transcript.


Subject(s)
Protein Serine-Threonine Kinases , Protein-Tyrosine Kinases/genetics , Amino Acid Sequence , Animals , Base Sequence , Blotting, Northern , Blotting, Southern , Cell Differentiation , Cloning, Molecular , DNA/genetics , Gene Expression , Mice , Molecular Sequence Data , Nuclear Proteins/genetics , Protein-Tyrosine Kinases/metabolism , Recombinant Fusion Proteins/metabolism , Substrate Specificity , Tumor Cells, Cultured
18.
Ann Thorac Surg ; 50(1): 29-33; discussion 33-4, 1990 Jul.
Article in English | MEDLINE | ID: mdl-2369225

ABSTRACT

Subvalvar aortic stenosis can be associated with progressive left ventricular outflow tract obstruction, aortic insufficiency, and infective endocarditis. We reviewed the records of 36 surgical patients who underwent 39 operations for subaortic stenosis. Seventeen patients had associated congenital cardiac anomalies. One perioperative death occurred in a patient with tetralogy of Fallot. The mean preoperative left ventricular outflow tract systolic pressure gradient was 64 +/- 5 mm Hg (+/- standard error of the mean) and decreased to 9 +/- 2 mm Hg postoperatively (p less than 0.001). Reliable preoperative and postoperative information regarding aortic valve function was available for 27 patients. Aortic insufficiency was found in 17 (63%) of those patients preoperatively. Postoperatively, insufficiency increased in 3 patients and decreased in 4; none of these changes was major. Severity of preoperative aortic insufficiency increased significantly with age (p less than 0.05), but did not correlate with left ventricular outflow tract gradient. The information from this study and previous studies suggests that resection of subaortic stenosis is safe and effective, and operation at the time of diagnosis, regardless of left ventricular outflow tract gradient or symptomatic status, is a reasonable therapeutic alternative.


Subject(s)
Aortic Stenosis, Subvalvular/surgery , Cardiomyopathy, Hypertrophic/surgery , Ventricular Outflow Obstruction/surgery , Adolescent , Adult , Aortic Stenosis, Subvalvular/physiopathology , Aortic Valve Insufficiency/physiopathology , Aortic Valve Insufficiency/surgery , Blood Pressure/physiology , Cardiac Output/physiology , Cardiac Surgical Procedures , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Recurrence , Retrospective Studies , Time Factors , Ventricular Outflow Obstruction/physiopathology
19.
J Vasc Surg ; 5(4): 544-50, 1987 Apr.
Article in English | MEDLINE | ID: mdl-3560350

ABSTRACT

Previous reports have demonstrated that endothelial cell seeding of polytetrafluoroethylene (PTFE) grafts enhances short-term patency. This experiment was undertaken to study its impact on the long-term patency of a highly porous, experimental PTFE graft and to determine whether increasing the internodal distance of the graft material resulted in increased proliferation of the subendothelium. Ten centimeter long, 4 mm internal diameter segments of an unreinforced, experimental PTFE graft were implanted into 36 mongrel dogs as carotid interpositions. In each animal, one graft was seeded with autologous endothelial cells, enzymatically derived from the external jugular veins, whereas the contralateral graft was treated in identical fashion except that endothelial cells were not added to the preclot mixture. Nineteen animals were killed at 12 weeks; six at 22 weeks; eight at 26 weeks; and three at 52 weeks. The mean follow-up period was 20.1 weeks. The overall patency rate was 58.3% (21 of 36 grafts) for seeded grafts vs. 27.8% (10 of 36 grafts) for control grafts (p less than 0.01). The thrombus-free area was planimetrically measured at 83.4% +/- 4.5% in seeded grafts vs. 55.1% +/- 9.7% in control grafts (p less than 0.05). Scanning electron microscopy confirmed the presence of a confluent cellular monolayer in seeded grafts, whereas control grafts exhibited a variable coagulum of fibrin, platelets, and endothelial cells. The thickness of the subendothelial layer varied from 56 to 95 micron with no progressive increase in thickness between 12 and 52 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Blood Vessel Prosthesis , Endothelium/cytology , Graft Occlusion, Vascular/prevention & control , Polytetrafluoroethylene , Animals , Carotid Arteries/surgery , Dogs , Graft Occlusion, Vascular/pathology , Time Factors , Vascular Patency
20.
J Surg Res ; 42(2): 185-91, 1987 Feb.
Article in English | MEDLINE | ID: mdl-3821083

ABSTRACT

Although there has been much recent interest in the application of lasers to arterial occlusive disease, a detailed understanding of the effects of laser energy on vessel walls is lacking. This study compared the effect of a conventional, non-contact delivery system of Nd:YAG laser energy to a contact system using a 600 microns, artificial sapphire tip in eight mongrel dogs. A small section of the luminal surface of the carotid and femoral arteries was exposed to 10 or 15 joules of Nd:YAG laser power and flow was restored in the vessel. The animals were sacrificed at 0, 1, 2, 4, 7, 14, 21, and 30 days and the vessels were removed. The surface area of the laser injury for each artery was quantitated by computerized planimetry and all histologic sections were examined under light microscopy by an independent observer. Transmural necrosis occurred in 64% (20/31) of the non-contact lesions versus only 29% (9/31) of the contact lesions (P less than 0.01). Both types of laser injuries followed a predictable course with initial medial necrosis followed by formation of a fibrin erythrocyte coagulum overlying the lesions at 24 hr. The usual zones of vaporization, coagulation necrosis, and thermal damage were noted with both types of delivery systems, but the contact system resulted in more intimal vaporization. Healing of all lesions was rapid with complete endothelial coverage at two weeks. Thrombosis occurred in only 1 of 32 (3%) arteries, and there were no false aneurysms. Contact delivery of Nd:YAG laser energy produces significantly less transmural injury than does non-contact.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Blood Vessels/physiology , Laser Therapy/instrumentation , Vascular Surgical Procedures/instrumentation , Wound Healing , Animals , Dogs
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