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1.
Ann Vasc Surg ; 78: 377.e5-377.e10, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34461239

ABSTRACT

OBJECTIVES: To propose a contemporary management strategy for venous injury during anterior lumbar spinal exposure that incorporates endovascular treatment. METHODS: Vein injuries suffered by patients treated in a single practice were reviewed. A treatment algorithm based on these experiences was formulated. RESULTS: Between 2015 and 2018, 914 patients received anterior access procedures for indicated lumbar interbody fusions. Of these patients, 15 (1.6%) suffered minor vascular injuries treated with manual pressure or suture repair. Four (0.4%) patients undergoing anterior lumbar spine surgery suffered major venous injuries, all of whom received the indicated spinal hardware following endovascular rescue. Primary repair was attempted in three patients before endovascular control and not at all in one. Vascular access was obtained via the bilateral femoral veins in 2 patients, unilateral femoral in one, and bilateral femoral plus right internal jugular vein in one. Stent choice included both uncovered (5, 63%) and covered stents (3, 38%). Deep venous thrombosis occurred in 2 patient's post-treatment. 1 DVT was encountered in the setting of a covered stent and 1 uncovered stent thrombosis was treated with catheter-directed lysis 4 weeks post-operatively. Ultimately, 3 patients were therapeutically anticoagulated. Mean follow-up is 13 months (range 1-36) with duplex ultrasounds available at 6 months or later in 3 of 4 patients. There is no evidence of post-thrombotic syndrome in the 2 patients that developed DVT's or in-stent stenosis in the 3 patients with available follow-up imaging. CONCLUSIONS: Endovascular techniques are important adjuncts when controlling large-volume hemorrhage associated with venous tears during anterior spinal exposure. Adequate direct compression allowing occlusion balloon inflation are key steps to reduce blood loss. Covered and uncovered stents are both appropriate choices to treat injuries. Patients must be anticoagulated post-operatively and surveilled for the sequelae of venous insufficiency. With expedient hemostasis, the indicated spinal surgery may be safely completed.


Subject(s)
Blood Loss, Surgical/prevention & control , Endovascular Procedures , Hemostatic Techniques , Iliac Vein/injuries , Lumbar Vertebrae/surgery , Spinal Fusion/adverse effects , Vascular System Injuries/therapy , Adult , Anticoagulants/therapeutic use , Endovascular Procedures/adverse effects , Endovascular Procedures/instrumentation , Female , Hemostatic Techniques/instrumentation , Humans , Male , Middle Aged , Postthrombotic Syndrome/drug therapy , Postthrombotic Syndrome/etiology , Stents , Treatment Outcome , Vascular System Injuries/diagnosis , Vascular System Injuries/etiology , Venous Thrombosis/drug therapy , Venous Thrombosis/etiology , Young Adult
2.
J Hand Surg Am ; 47(5): 476.e1-476.e6, 2022 05.
Article in English | MEDLINE | ID: mdl-34247847

ABSTRACT

PURPOSE: To compare lag versus nonlag screw fixation for long oblique proximal phalanx (P1) fractures in a cadaveric model of finger motion via the flexor and extensor tendons. METHODS: We simulated long oblique P1 fractures with a 45° oblique cut in the index, middle, and ring fingers of 4 matched pairs of cadaveric hands for a total of 24 simulated fractures. Fractures were stabilized using 1 of 3 techniques: two 1.5-mm fully threaded bicortical screws using a lag technique, two 1.5-mm fully threaded bicortical nonlag screws, or 2 crossed 1.14-mm K-wires as a separate control. The fixation method was randomized for each of the 3 fractures per matched-pair hand, with each fixation being used in each hand and 8 total P1 fractures per fixation group. Hands were mounted to a custom frame where a computer-controlled, motor-driven, linear actuator powered movement of the flexor and extensor tendons. All fingers underwent 2,000 full flexion and extension cycles. Maximum interfragmentary displacement was continuously measured using a differential variable reluctance transducer. Our primary outcome was the difference in the mean P1 fragment displacement between lag and nonlag screw fixation at 2,000 cycles. RESULTS: The observed differences in mean displacement between lag and nonlag screw fixation were not statistically significant throughout all time points. A two one-sided test procedure for paired samples confirmed statistical equivalence in the fragment displacement between these fixation methods at all time points, including the primary end point of 2,000 cycles. CONCLUSIONS: Nonlag screws provided equivalent biomechanical stability to lag screws for simulated long oblique P1 fractures during cyclic testing in this cadaveric model. CLINICAL RELEVANCE: Fixation of long oblique P1 fractures with nonlag screws has the potential to simplify treatment without sacrificing fracture stability during immediate postoperative range of motion.


Subject(s)
Fracture Fixation, Internal , Fractures, Bone , Biomechanical Phenomena , Bone Screws , Cadaver , Fracture Fixation, Internal/methods , Fractures, Bone/surgery , Humans
3.
Crit Care Nurs Q ; 44(4): 368-378, 2021.
Article in English | MEDLINE | ID: mdl-34437315

ABSTRACT

Determining the treatment plan and how to successfully manage a patient suffering from an acute ischemic stroke can be challenging for a registered nurse (RN) in the emergency department. Using a mnemonic in the treatment process assists in reducing medical errors and increases the likelihood of making positive clinical outcomes. Mnemonics sum up complex strategies into relevant information that can be comprehensible for users. The authors have created a mnemonic strategy to provide RNs in the emergency department with a structured approach to the pharmacotherapeutic strategies used in treating patients with an acute ischemic stroke. All guidelines used throughout the article are in concurrence.


Subject(s)
Brain Ischemia , Ischemic Stroke , Stroke , Brain Ischemia/drug therapy , Emergency Service, Hospital , Humans , Stroke/drug therapy
4.
Lab Anim ; 51(6): 656-659, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28669255

ABSTRACT

Record keeping within research animal care facilities is a key part of the guidelines set forth by national regulatory bodies and mandated by federal laws. Research facilities must maintain records of animal health issues, procedures and usage. Facilities are also required to maintain records regarding regular husbandry such as general animal checks, feeding and watering. The level of record keeping has the potential to generate excessive amounts of paper which must be retained in a fashion as to be accessible. In addition it is preferable not to retain within administrative areas any paper records which may have been in contact with animal rooms. Here, we present a flexible, simple and inexpensive process for the generation and storage of electronic animal husbandry records using smartphone technology over a WiFi or cellular network.


Subject(s)
Animal Husbandry/methods , Computers, Handheld , Electronic Data Processing/instrumentation , Animal Husbandry/instrumentation , Animals , Computers, Handheld/statistics & numerical data , Manitoba
5.
Issues Ment Health Nurs ; 37(9): 642-650, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27128141

ABSTRACT

Alcohol and substance abuse remain significant public health problems in many parts of the occidental world. Some facilities that provide treatment for such abuse often refer to themselves as "Therapeutic Communities" (TCs). However, fundamental compositional differences in TCs present unresolved issues and as such, create significant implications for research, practice, education, and substance/alcohol care policy. Accordingly, this paper examines the heterogeneity and efficacy of TCs; the treatment approaches of harm reduction and abstinence; the training of TC staff and workers; and the recommended length of stay for individuals seeking recovery.

6.
Semin Intervent Radiol ; 32(1): 18-21, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25762843

ABSTRACT

Nontarget embolization is a relatively common cause of post-chemoembolization complications. Clinical presentation following nontarget embolization varies from minimal to fatal, and oftentimes relates to the vascular distribution embolized rather than the amount or type of embolic agent. Post-chemoembolization pancreatitis is an uncommon complication, but one that is known to occur. The following manuscript presents a case of post-chemoembolization pancreatitis, and suggests methods to decrease this complication as well as treatment once the complication occurs.

7.
AJR Am J Roentgenol ; 204(2): 440-7, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25615768

ABSTRACT

OBJECTIVE. The purpose of this study was to determine the overall survival rates in patients with advanced hepatocellular carcinoma (HCC) who undergo treatment with drug-eluting bead (DEB) therapy. MATERIALS AND METHODS. A retrospective review of the clinical HCC database of a single institution was undertaken for patients treated between September 2008 and December 2011. Demographic information, laboratory and imaging findings, procedural details, and outcomes after treatment were obtained. The primary outcome was overall survival, which was stratified by Barcelona Clinic Liver Cancer (BCLC) stage, Child-Pugh class, Eastern Cooperative Oncology Group (ECOG) score, serum bilirubin level, and ethnicity. Multiple secondary independent variables were also measured. RESULTS. Of 239 consecutive patients treated during the prescribed time frame, 43 patients met the inclusion criteria. Thirty patients met the criteria for BCLC stage C, and 13 met the criteria for BCLC stage D based largely on ECOG score. Eight patients had venous invasion or portal venous thrombosis, and four had limited extrahepatic metastases. Eight patients had Child-Pugh class C liver disease but remained candidates for liver transplant based on the Milan criteria. The median overall survival was 596 days; 23 patients are still alive, 12 of whom underwent liver transplant. The only independent variables affecting survival were serum bilirubin value of 2.0 mg/dL or greater (hazard ratio [HR] = 3.96; 95% CI, 1.46-10.7; p = 0.007) and Child-Pugh class B or C disease (HR = 3.33; 95% CI, 1.07-10.34; p = 0.037). CONCLUSION. The use of DEBs for TACE therapy is safe and effective in carefully selected patients with advanced HCC.


Subject(s)
Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/therapy , Chemoembolization, Therapeutic , Drug Carriers , Liver Neoplasms/mortality , Liver Neoplasms/therapy , Adult , Aged , Aged, 80 and over , Carcinoma, Hepatocellular/pathology , Female , Humans , Liver Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Retrospective Studies , Survival Rate , Treatment Outcome
8.
Contraception ; 90(6): 606-8, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25081861

ABSTRACT

Despite modifications to avoid deep insertions, clinical experience with Nexplanon demonstrates that deep insertions still occur. We present a case of a Nexplanon found in the biceps muscle that was successfully removed with a small incision using a combination of ultrasound and fluoroscopy guidance by interventional radiologists.


Subject(s)
Contraceptive Agents, Female , Desogestrel , Device Removal , Drug Implants , Adult , Arm , Female , Fluoroscopy , Humans , Muscle, Skeletal/surgery , Ultrasonography, Interventional
9.
J Vasc Interv Radiol ; 24(11): 1613-22, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24060436

ABSTRACT

PURPOSE: To assess downstaging rates in patients with United Network for Organ Sharing stage T3N0M0 hepatocellular carcinoma (HCC) treated with doxorubicin-eluting bead transarterial chemoembolization to meet Milan criteria for transplantation. MATERIALS AND METHODS: A single-center retrospective review of 239 patients treated with doxorubicin-eluting bead (DEB) chemoembolization between September 2008 and December 2011 was undertaken. Baseline and follow-up computed tomography or magnetic resonance imaging was assessed for response based on the longest enhancing axial dimension of each tumor (ie, modified Response Evaluation Criteria In Solid Tumors measurements), and medical records were reviewed. Fisher exact tests and exact logistic regression were used to test the association of patient and disease characteristics with downstaging. RESULTS: After exclusions, 22 patients remained in the analysis, 17 of whom (77%) had their HCC downstaged to meet Milan criteria. Among those whose disease was downstaged, seven underwent transplantation, one remained listed for transplantation, six had disease progression beyond Milan criteria, two underwent conventional transarterial chemoembolization, and one underwent radiofrequency ablation. The seven patients who received transplants were still living, but recurrent HCC developed in two. Baseline age (P = .25), Model for End-stage Liver Disease score (P = .77), and α-fetoprotein (AFP) level (P = 1.00) were similar between patients with and without downstaged HCC. No associations were observed between the odds of downstaging and sex (P = .21), Child-Pugh class (P = .14), Child-Pugh class controlling for baseline tumor multiplicity (P = .15), Eastern Cooperative Oncology Group performance status (P = 1.00), tumor burden (P = .31), multiple tumors (P = .31), or hepatitis C virus infection (P = 1.00). Fifteen patients who did not receive transplants were alive at 1 year, with two progression-free. Baseline AFP levels differed between those who survived 1 year and those who did not (P = .02), but did not differ by progression-free survival status (P = .62). CONCLUSIONS: T3N0M0 HCC treatment with DEB chemoembolization has a high likelihood (77%) of downstaging the disease to meet Milan criteria.


Subject(s)
Antibiotics, Antineoplastic/administration & dosage , Carcinoma, Hepatocellular/therapy , Chemoembolization, Therapeutic , Doxorubicin/administration & dosage , Liver Neoplasms/therapy , Liver Transplantation , Neoadjuvant Therapy , Aged , Antibiotics, Antineoplastic/adverse effects , Carcinoma, Hepatocellular/blood , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/surgery , Catheter Ablation , Chemoembolization, Therapeutic/adverse effects , Chemoembolization, Therapeutic/mortality , Chemotherapy, Adjuvant , Colorado , Disease Progression , Disease-Free Survival , Doxorubicin/adverse effects , Female , Humans , Liver Neoplasms/blood , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Liver Neoplasms/surgery , Liver Transplantation/adverse effects , Liver Transplantation/mortality , Logistic Models , Magnetic Resonance Imaging , Male , Middle Aged , Neoplasm Recurrence, Local , Neoplasm Staging , Odds Ratio , Retrospective Studies , Risk Factors , Time Factors , Tomography, X-Ray Computed , Treatment Outcome , alpha-Fetoproteins/metabolism
10.
Int Forum Allergy Rhinol ; 3(11): 921-7, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23881553

ABSTRACT

BACKGROUND: Bronchiectasis is an uncommon disease of the lower airways characterized by bronchial wall destruction and permanent bronchiolar dilation. Several etiologic categories exist, and patients with bronchiectasis often complain of symptoms suggestive of chronic rhinosinusitis (CRS). The present study investigates the association between bronchiectasis and CRS using radiologic and bacteriologic data. METHODS: Retrospective chart review from a tertiary care respiratory hospital was performed. Sinus computed tomography (CT) scans were examined for extent of disease and relationship to pulmonary disease severity. Statistical analysis was performed with Student t test and linear regression. Upper and lower airway cultures from patients with both bronchiectasis and CRS were compared using the chance adjusted agreement. RESULTS: Patients with bronchiectasis were found to have a significantly higher Lund-Mackay score when compared to patients with allergic rhinitis (p = 0.047). Lund-Mackay CT score did not correlate with forced expiratory volume in 1 second (FEV1 ) and FEV1 :forced vital capacity (FVC), or presence of Pseudomonas aeruginosa. Correlation of upper and lower airway bacterial cultures in patients with both bronchiectasis and CRS was noted (kappa = 0.294, p = 0.004), particularly when P. aeruginosa was present (kappa = 0.49, p < 0.0001). CONCLUSION: The current study suggests that the upper and lower airways may be linked in CRS and bronchiectasis from both an objective radiologic standpoint and a bacteriologic perspective. This finding carries implications for disease pathogenesis, clinical care, and future research.


Subject(s)
Bronchiectasis , Respiratory System , Rhinitis , Sinusitis , Sputum/microbiology , Adolescent , Adult , Aged , Aged, 80 and over , Bronchiectasis/complications , Bronchiectasis/diagnostic imaging , Bronchiectasis/microbiology , Chronic Disease , Female , Forced Expiratory Volume , Humans , Male , Middle Aged , Pseudomonas aeruginosa/isolation & purification , Respiratory System/diagnostic imaging , Respiratory System/microbiology , Retrospective Studies , Rhinitis/complications , Rhinitis/diagnostic imaging , Rhinitis/microbiology , Sinusitis/complications , Sinusitis/diagnostic imaging , Sinusitis/microbiology , Tomography, X-Ray Computed/methods , Vital Capacity , Young Adult
11.
J Vasc Interv Radiol ; 23(6): 801-8, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22459879

ABSTRACT

PURPOSE: To determine if noncontrast T1-weighted (T1W) images from 3T magnetic resonance (MR) imaging accurately depict radiofrequency (RF) ablation zones as determined macroscopically and microscopically in a blood-perfused bovine liver model. MATERIALS AND METHODS: Three-dimensional (3D) gradient-recalled echo (GRE) T1W images were obtained on a 3T MR imaging scanner after RF ablations (n = 14) of in vitro blood-perfused bovine livers. The resulting central hypointense and peripheral hyperintense signal regions were measured and compared with the inner tan and outer red zones of the gross specimen. Corresponding ablated hepatic tissue samples were examined microscopically and stained with nicotinamide adenine dinucleotide phosphate (NADPH) to assess for the presence or absence of NADPH diaphorase activity. Bootstrap two-sample hypothesis tests were used to compare MR imaging, gross, and histopathologic measurements. RESULTS: The MR imaging inner ablation zone had a mean radius of 0.80 cm (range 0.33-1.14 cm); the inner zone plus the outer ablation zone had a mean radius of 1.40 cm (range 1.01-1.74 cm). Comparison of the measurements of the inner ablation zone on MR imaging versus the gross specimen showed equivalence (95% confidence interval [CI] -0.122 cm, 0.223 cm). Comparison of the measurements of the outer ablation zone on MR imaging versus the gross and histologic specimens also showed equivalence (95% CI -0.095 cm, 0.244 cm, and -0.146 cm, 0.142 cm). CONCLUSIONS: Noncontrast 3D GRE T1W 3T MR imaging accurately depicts the RF ablation zones in a blood-perfused bovine liver model and can be used as a noninvasive means to assess the 3D morphologic characteristics of RF ablation lesions in the model.


Subject(s)
Catheter Ablation , Image Interpretation, Computer-Assisted , Imaging, Three-Dimensional , Liver Circulation , Liver/blood supply , Liver/surgery , Magnetic Resonance Imaging , Perfusion , Animals , Cattle , Liver/enzymology , Liver/pathology , Models, Animal , NADPH Dehydrogenase/analysis , Staining and Labeling
12.
Inorg Chem ; 51(5): 2777-84, 2012 Mar 05.
Article in English | MEDLINE | ID: mdl-22339702

ABSTRACT

The direct intercalation of a pyrazolate-bridged platinum(II) bipyridyl dimer ([{Pt(dmbpy)(µ-pz)}(2)](2+); dmbpy = 4,4'-dimethyl-2,2'-bipyridine, pz(-) = pyrazolate) within a zirconium phosphate (ZrP) framework has been accomplished. The physical and spectroscopic properties of [{Pt(dmbpy)(µ-pz)}(2)](2+) intercalated in ZrP were investigated by X-ray powder diffraction and X-ray photoelectron, infrared, absorption, and luminescence spectroscopies. Zirconium phosphate layers have a special microenvironment that is capable of supporting a variety of platinum oxidation states. Diffuse reflectance spectra from powders of the blue-gray intercalated materials show the formation of a low-energy band at 600 nm that is not present in the platinum dimer salt. The nonintercalated complex is nonemissive in room-temperature fluid solution, but gives rise to intense blue-green emission in a 4:1 ethanol/methanol 77 K frozen glassy solution. Powders and colloidal suspensions of [{Pt(dmbpy)(µ-pz)}(2)](2+)-exchanged ZrP materials exhibit intense emissions at room-temperature.

13.
J Vasc Interv Radiol ; 22(10): 1478-83, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21802317

ABSTRACT

PURPOSE: To describe an in vitro blood-perfused bovine liver model for the testing of radiofrequency (RF) ablation devices and compare the performance of a specific RF ablation device in the model relative to three other biologic models. MATERIALS AND METHODS: Fresh bovine livers were used to create three in vitro models: blood-perfused, Krebs-Henseleit (KH) solution-perfused, and nonperfused. The perfused models were connected to a heart-lung machine via the portal vein and perfused with heparinized autologous blood or KH solution under physiologic conditions. Six swine were used as in vivo liver models. A cluster electrode and RF ablation system was operated in impedance mode for 12 minutes in all models. Ablated livers were sectioned, with long- and short-axis measurements of the ablations obtained, and statistical analysis was performed. RESULTS: A total of 39, 23, 17, and 12 ablations were performed in 14, 6, 5, and 6 blood-perfused bovine livers, KH solution-perfused bovine livers, nonperfused bovine livers, and in vivo porcine livers, respectively. On cut specimens, the average diameters of ablation zones were 4.00 cm (95% CI, 3.88-4.13) in blood-perfused livers, 4.34 cm (95% CI, 4.14-4.50) in KH solution-perfused livers, 4.67 cm (95% CI, 4.50-4.83) in nonperfused livers, and 3.56 cm (95% CI, 3.26-3.83) in in vivo porcine livers. In all models, the ablation zone diameters were normally distributed. CONCLUSIONS: In the in vitro blood-perfused bovine liver model, the size of ablations produced by an RF ablation device are closer in size to those seen in porcine liver in vivo compared with the lesions produced in KH solution-perfused or nonperfused bovine liver.


Subject(s)
Catheter Ablation/instrumentation , Liver Circulation , Liver/surgery , Perfusion/methods , Animals , Cattle , Equipment Design , Glucose , In Vitro Techniques , Liver/blood supply , Liver/pathology , Materials Testing , Models, Animal , Swine , Tromethamine
14.
Global Health ; 5: 4, 2009 Feb 26.
Article in English | MEDLINE | ID: mdl-19245698

ABSTRACT

BACKGROUND: Each year medical providers from wealthy countries participate in short-term medical volunteer work in resource-poor countries. Various authors have raised concern that such work has the potential to be harmful to recipient communities; however, the social science and medical literature contains little research into the perceptions of short-term medical volunteer work from the perspective of members of recipient communities. This exploratory study examines the perception of short-term medical volunteer work in Guatemala among groups of actors affected by or participating in these programs. METHODS: The researchers conducted in-depth, semi-structured interviews with 72 individuals, including Guatemalan healthcare providers and health authorities, foreign medical providers, non-medical personnel working on health projects, and Guatemalan parents of children treated by a short-term volunteer group. Detailed notes and summaries of these interviews were uploaded, coded and annotated using Atlas.ti (Scientific Software Development GmbH, Berlin) to identify recurrent themes from the interviews. RESULTS: Informants commonly identified a need for increased access to medical services in Guatemala, and many believed that short-term medical volunteers are in a position to offer improved access to medical care in the communities where they serve. Informants most frequently cited appropriate patient selection and attention to payment systems as the best means to avoid creating dependence on foreign aid. The most frequent suggestion to improve short-term medical volunteer work was coordination with and respect for local Guatemalan healthcare providers and their communities, as insufficient understanding of the country's existing healthcare resources and needs may result in perceived harm to the recipient community. CONCLUSION: The perceived impact of short-term medical volunteer projects in Guatemala is highly variable and dependent upon the individual project. In this exploratory study, project characteristics were identified that are consistently perceived to be either positive or negative. These findings have direct implications for anyone involved in the planning and execution of short-term medical volunteer projects, including local and foreign medical team members, project planners and coordinators, and health authorities. Most importantly, this preliminary study suggests avenues for future study and evaluation of the impact of short-term medical volunteer programs on local health care services.

15.
Carcinogenesis ; 29(5): 905-12, 2008 May.
Article in English | MEDLINE | ID: mdl-18299279

ABSTRACT

The type III transforming growth factor-beta receptor (TbetaRIII or betaglycan) is a ubiquitously expressed transforming growth factor-beta (TGF-beta) superfamily coreceptor with essential roles in embryonic development. Recent studies have defined a role for TbetaRIII in the pathogenesis of human cancers, with frequent loss of TbetaRIII expression at the message and protein level. Mechanisms for the loss of TbetaRIII expression remain to be fully defined. Advanced human cancers often have elevated circulating levels of TGF-beta1. Here, we define a specific role for TGF-beta1 in negatively regulating TbetaRIII at the message level in breast and ovarian cancer models. TGF-beta1 decreased TbetaRIII message and protein levels in ovarian (Ovca420) and breast cancer (MDA-MB-231) cell lines in both a dose- and time-dependent manner. TGF-beta1-mediated TbetaRIII repression is mediated by the type I TGF-beta receptor/Smad2/3 pathway as the activin receptor-like kinase 5 (ALK5) inhibitor, SB431542, abrogated this effect, while the expression of constitutively active ALK5 was sufficient to repress TbetaRIII expression. Mechanistically, TGF-beta1 does not affect TbetaRIII messenger RNA (mRNA) stability, but instead directly regulates the TbetaRIII promoter. We define alternative promoters for the TGFBR3 gene, a distal and proximal promoter. Although both promoters are active, only the proximal promoter was responsive and negatively regulated by TGF-beta1 and constitutively active ALK5. Taken together, these studies define TGF-beta1-mediated downregulation of TbetaRIII mRNA expression through effects on the ALK5/Smad2/3 pathway on the TGFBR3 gene proximal promoter as a potential mechanism for decreased TbetaRIII expression in human cancers.


Subject(s)
Promoter Regions, Genetic , Proteoglycans/genetics , Receptors, Transforming Growth Factor beta/genetics , Transforming Growth Factor beta1/physiology , Benzamides/pharmacology , Breast Neoplasms , Cell Line, Tumor , DNA Primers , DNA, Complementary/genetics , Dioxoles/pharmacology , Female , Gene Expression Regulation , Genes, Reporter , Humans , Ovarian Neoplasms , Protein Kinase Inhibitors/pharmacology , RNA, Messenger/genetics , RNA, Neoplasm/genetics , RNA, Neoplasm/isolation & purification , Receptors, Transforming Growth Factor beta/antagonists & inhibitors , Reverse Transcriptase Polymerase Chain Reaction
16.
Inorg Chem ; 44(6): 1955-65, 2005 Mar 21.
Article in English | MEDLINE | ID: mdl-15762722

ABSTRACT

Five platinum(II) 1,4,7-trithiacyclononane (ttcn) complexes with bidentate-substituted 2,2'-bipyridine ligands have been prepared and structurally characterized: [Pt(bpy)(ttcn)](PF6)2 (bpy = 2,2'-bipyridine), triclinic, P1, a = 10.2529(3) A, b = 10.7791(3) A, c = 10.7867(3) A, alpha = 83.886(1) degrees, beta = 87.565(1) degrees, gamma = 84.901(1), V = 1179.99(6) A3, Z = 2; [Pt(4,4'-dmbpy)(ttcn)](PF6)2 x CH3CN x H2O (4,4'-dmbpy = 4,4'-dimethyl-2,2'-bipyridine), triclinic, P1, a = 10.1895(3) A, b = 11.8566(4) A, c = 13.1004(4) A, alpha = 77.345(1) degrees, beta = 79.967(1) degrees, gamma = 72.341(1) degrees, V = 1461.56(8) A3, Z = 2; [Pt(5,5'-dmbpy)(ttcn)](PF6)2 (5,5'-dmbpy = 5,5'-dimethyl-2,2'-bipyridine), triclinic, P1, a = 10.6397(4) A, b = 10.8449(4) A, c = 11.2621(4) A, alpha = 90.035(1) degrees, beta = 98.061(1) degrees, gamma = 91.283(1) degrees, V = 1286.32(8) A3, Z = 2; [Pt(dbbpy)(ttcn)](PF6)2 x CH3NO2 (dbbpy = 4,4'-di-tert-butyl-2,2'-bipyridine), triclinic, P1, a = 11.5422(7) A, b = 11.6100(7) A, c = 13.6052(9) A, alpha = 85.902(1) degrees, beta = 89.675(1) degrees, gamma = 74.942(1) degrees, V = 1755.90(19) A3, Z = 2; and [Pt(dtfmbpy)(ttcn)](PF6)2 x CH3CN (dtfmbpy = 5,5'-di-trifluoromethyl-2,2'-bipyridine): monoclinic, P2(1)/c, a = 13.1187(9) A, b = 20.9031(15) A, c = 11.3815(8) A, beta = 105.789(2) degrees, V = 3003.3(4) A3, Z = 4. For each salt, the platinum(II) center of the cation is bonded to two nitrogen atoms of the chelating diimine and two sulfur atoms of the thioether macrocycle. The third sulfur atom of ttcn forms a long apical interaction with the metal center (2.84-2.97 A), resulting in a flattened square pyramid structure. An examination of these and 17 other structures of platinum(II) ttcn complexes reveals a correlation between the apical Pt...S distance and the donor properties of the ancillary ligands, suggesting a means for using variations in ligand electronic properties to tune molecular structure. The room-temperature absorption spectra in acetonitrile solution show a broad and comparatively low-energy MLCT band maximizing near approximately 390 nm for the bpy and dialkyl-substituted bipyridyl derivatives. The maximum is dramatically red-shifted to 460 nm in the spectrum of the dtfmbpy complex as a result of the electron-withdrawing properties of the -CF(3) groups. The 3:1 EtOH/MeOH 77 K glassy solution emission spectra exhibit low-energy emission bands (lambdamax, 570-645 nm), tentatively assigned as originating from a lowest, predominantly spin-forbidden MLCT excited state that is stabilized by apical Pt...S interactions.

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