The LTAR cropland common experiment in the Lower Mississippi River Basin.

The Lower Mississippi River Basin-Long-Term Agroecosystem Research Site (LMRB-LTAR) encompasses six states from Missouri to the Gulf of Mexico and is coordinated by the USDA-ARS National Sedimentation Laboratory, Oxford, MS. The overarching goal of LTAR is to assess regionally diverse and geographically scalable farming practices for enhanced sustainability of agroecosystem goods and services under changing environment and resource-use conditions. The LMRB-LTAR overall goal is to assess sustainable row crop agricultural production systems that integrate regional environmental and socioeconomic needs. Primary row crops in the region include soybeans, corn, cotton, rice, and sugarcane with crop rotations influenced by commodity crop price and other factors. The field-scale common experiment (CE) includes four row crop farms (26-101 ha) established in 2021 and 2023. Three fields are managed with alternative practices, including reduced tillage, cover crops, and automated prescription irrigation, and three fields are managed with prevailing farming practices, consisting of conventional tillage, no cover crop, and nonprescription irrigation. Treatment effects on crop productivity, soil quality, water use efficiency, water quality, and carbon storage are assessed. Research from the LMRB CE will deliver outcomes linked to overarching LTAR network goals, including innovative agricultural systems, strengthened partnerships, data management technologies, and precision environmental tools.

Comparative analysis of three next-generation sequencing techniques to measure nosZ gene abundance in Missouri claypan soils.

Quantitative next-generation sequencing techniques have been critical in gaining a better understanding of microbial ecosystems. In soils, denitrifying microorganisms are responsible for dinitrogen (N2) production. The nosZ gene codes for nitrous oxide reductase, the enzyme facilitating the reduction of nitrous oxide (N2O) to N2. The objectives of this research were to: 1) understand how soil depth influences RNA concentration and nosZ gene abundance; 2) assess the spatial dependence of nosZ gene abundance in two claypan soil fields; and 3) compare and evaluate multiple RNA-based sequencing methods for quantifying nosZ gene abundance in soils in relation to dinitrogen (N2) production. Research sites consisted of two intensively studied claypan soil fields in Central Missouri, USA. Soil cores were collected from two landscape transects across both fields and analyzed for extractable soil RNA at two depths (0-15 cm and 15-30 cm). Measurements of nosZ gene abundance were obtained using real-time quantitative polymerase chain reaction (RT-qPCR), droplet digital polymerase chain reaction (ddPCR), and nanostring sequencing (NS). In both fields, soil RNA concentrations were significantly greater at 0-15 cm depth compared to 15-30 cm. These data indicated low overall soil microbial activity below 15 cm. Due to low quantities of extractable soil RNA in the subsoil, nosZ gene abundance was only determined in the 0-15 cm depth. Sequencing method comparisons of average nosZ gene abundance showed that NS results were constrained to a narrow range and were 10-20-fold lower than ddPCR and RT-qPCR at each landscape position within each field. Droplet digital PCR appears to be the most promising method, as it reflected changes in N2 production across landscape position.

Development of the LYVE-1 gene with an acidic-amino-acid-rich (AAAR) domain in evolution is associated with acquisition of lymph nodes and efficient adaptive immunity.

CRSBP-1 (mammalian LYVE-1) is a membrane glycoprotein highly expressed in lymphatic endothelial cells (LECs). It has multiple ligands, including hyaluronic acid (HA) and growth factors/cytokines (e.g., PDGF-BB and VEGF-A) containing CRS motifs (clusters of basic amino-acid residues). The ligand binding activities are mediated by Link module and acidic-amino-acid-rich (AAAR) domains, respectively. These CRSBP-1/LYVE-1 ligands have been shown to induce opening of lymphatic intercellular junctions in LEC monolayers and in lymphatic vessels in wild-type mice. We hypothesize that CRSBP-1/LYVE-1 ligands, particularly CRS-containing growth factors/cytokines, are secreted by immune and cancer cells for lymphatic entry during adaptive immune responses and lymphatic metastasis. We have looked into the origin of the Link module and AAAR domain of LYVE-1 in evolution and its association with the development of lymph nodes and efficient adaptive immunity. Lymph nodes represent the only major recent innovation of the adaptive immune systems in evolution particularly to mammals and bird. Here we demonstrate that the development of the LYVE-1 gene with the AAAR domain in evolution is associated with acquisition of lymph nodes and adaptive immunity. LYVE-1 from other species, which have no lymph nodes, lack the AAAR domain and efficient adaptive immunity. Synthetic CRSBP-1 ligands PDGF and VEGF peptides, which contain the CRS motifs of PDGF-BB and VEGF-A, respectively, specifically bind to CRSBP-1 but do not interact with either PDGFßR or VEGFR2. These peptides function as adjuvants by enhancing adaptive immunity of pseudorabies virus (PRV) vaccine in pigs. These results support the notion that LYVE-1 is involved in adaptive immunity in mammals.

7-Dehydrocholesterol (7-DHC), But Not Cholesterol, Causes Suppression of Canonical TGF-ß Signaling and Is Likely Involved in the Development of Atherosclerotic Cardiovascular Disease (ASCVD).

For several decades, cholesterol has been thought to cause ASCVD. Limiting dietary cholesterol intake has been recommended to reduce the risk of the disease. However, several recent epidemiological studies do not support a relationship between dietary cholesterol and/or blood cholesterol and ASCVD. Consequently, the role of cholesterol in atherogenesis is now uncertain. Much evidence indicates that TGF-ß, an anti-inflammatory cytokine, protects against ASCVD and that suppression of canonical TGF-ß signaling (Smad2-dependent) is involved in atherogenesis. We had hypothesized that cholesterol causes ASCVD by suppressing canonical TGF-ß signaling in vascular endothelium. To test this hypothesis, we determine the effects of cholesterol, 7-dehydrocholesterol (7-DHC; the biosynthetic precursor of cholesterol), and other sterols on canonical TGF-ß signaling. We use Mv1Lu cells (a model cell system for studying TGF-ß activity) stably expressing the Smad2-dependent luciferase reporter gene. We demonstrate that 7-DHC (but not cholesterol or other sterols) effectively suppresses the TGF-ß-stimulated luciferase activity. We also demonstrate that 7-DHC suppresses TGF-ß-stimulated luciferase activity by promoting lipid raft/caveolae formation and subsequently recruiting cell-surface TGF-ß receptors from non-lipid raft microdomains to lipid rafts/caveolae where TGF-ß receptors become inactive in transducing canonical signaling and undergo rapid degradation upon TGF-ß binding. We determine this by cell-surface 125 I-TGF-ß-cross-linking and sucrose density gradient ultracentrifugation. We further demonstrate that methyl-ß-cyclodextrin (MßCD), a sterol-chelating agent, reverses 7-DHC-induced suppression of TGF-ß-stimulated luciferase activity by extrusion of 7-DHC from resident lipid rafts/caveolae. These results suggest that 7-DHC, but not cholesterol, promotes lipid raft/caveolae formation, leading to suppression of canonical TGF-ß signaling and atherogenesis. J. Cell. Biochem. 118: 1387-1400, 2017. © 2016 Wiley Periodicals, Inc.

Optimal Colostomy Placement in Spinal Cord Injury Patients.

Barring unusual circumstances, sigmoid colostomy is the optimal technique for management of defecation in spinal cord injury (SCI) patients. We sought to provide evidence that a sigmoid colostomy is not difficult to perform in SCI patients and has better long-term results. The St. Louis Department of Veterans Affairs has a Commission on Accreditation of Rehabilitation Facilities (CARF)-approved SCI Unit. We reviewed the operative notes on all SCI patients who received a colostomy for fecal management by three ASCRS-certified colorectal surgeons at the St. Louis Department of Veterans Affairs from January 1, 2007 to November 26, 2012. There were 27 operations for which the recorded indication for surgery suggested that the primary disorder was SCI. Fourteen had traumatic SCI of the thoracic and/or lumbar spine and were evaluable. Of these 14 patients, 12 had laparoscopic sigmoid colostomy and two had open sigmoid colostomy. We encountered one evaluable patient with a remarkably large amount of retroperitoneal bony debris who successfully underwent laparoscopic sigmoid colostomy. In conclusion, sigmoid colostomy is the consensus optimal procedure for fecal management in SCI patients. Laparoscopic procedures are preferred. Care providers should specify sigmoid colostomy when contacting a surgeon.

Ethanol Enhances TGF-ß Activity by Recruiting TGF-ß Receptors From Intracellular Vesicles/Lipid Rafts/Caveolae to Non-Lipid Raft Microdomains.

Regular consumption of moderate amounts of ethanol has important health benefits on atherosclerotic cardiovascular disease (ASCVD). Overindulgence can cause many diseases, particularly alcoholic liver disease (ALD). The mechanisms by which ethanol causes both beneficial and harmful effects on human health are poorly understood. Here we demonstrate that ethanol enhances TGF-ß-stimulated luciferase activity with a maximum of 0.5-1% (v/v) in Mv1Lu cells stably expressing a luciferase reporter gene containing Smad2-dependent elements. In Mv1Lu cells, 0.5% ethanol increases the level of P-Smad2, a canonical TGF-ß signaling sensor, by ∼ 2-3-fold. Ethanol (0.5%) increases cell-surface expression of the type II TGF-ß receptor (TßR-II) by ∼ 2-3-fold from its intracellular pool, as determined by I(125) -TGF-ß-cross-linking/Western blot analysis. Sucrose density gradient ultracentrifugation and indirect immunofluorescence staining analyses reveal that ethanol (0.5% and 1%) also displaces cell-surface TßR-I and TßR-II from lipid rafts/caveolae and facilitates translocation of these receptors to non-lipid raft microdomains where canonical signaling occurs. These results suggest that ethanol enhances canonical TGF-ß signaling by increasing non-lipid raft microdomain localization of the TGF-ß receptors. Since TGF-ß plays a protective role in ASCVD but can also cause ALD, the TGF-ß enhancer activity of ethanol at low and high doses appears to be responsible for both beneficial and harmful effects. Ethanol also disrupts the location of lipid raft/caveolae of other membrane proteins (e.g., neurotransmitter, growth factor/cytokine, and G protein-coupled receptors) which utilize lipid rafts/caveolae as signaling platforms. Displacement of these membrane proteins induced by ethanol may result in a variety of pathologies in nerve, heart and other tissues.

Adjuvant radiation therapy for breast cancer in patients with schizophrenia.

BACKGROUND: Schizophrenia affects approximately 1% of subjects in all populations studied thus far. We sought to evaluate how patients with schizophrenia who are later diagnosed with breast cancer fare when adjuvant radiation therapy (ART) is clinically indicated. METHODS: We searched patient treatment file, the national inpatient computer database of the Department of Veterans Affairs, to identify patients with schizophrenia who subsequently developed breast cancer. RESULTS: Forty patients had schizophrenia, who later developed breast cancer and were candidates for ART, according to well-established guidelines. Of the 40 patients who were considered candidates for ART, we found data about the decision to offer ART in 35; only 22 (63%) were offered ART and 5 of those 22 (23%) refused it. CONCLUSIONS: Patients with schizophrenia and breast cancer often do not understand the nature of their illnesses well. They often do not comply with recommended standard therapies such as ART. Treatment strategies that rely on ART are likely to be met with noncompliance. Breast-preserving treatment plans may be impractical. Initial radical surgery without ART may be preferable.

Intensity of follow-up after breast cancer surgery: low versus high?

The incidence of breast cancer has been on the rise in the United States over the past several decades. The advanced longevity of the population during this same time period, specifically of elderly women, translates to increases in the absolute number of women diagnosed with breast cancer yearly. This, in combination with decreasing mortality rates, has now led to an increase in the number of breast cancer survivors who need long-term follow-up. There has been significant debate over what tests should be obtained, how often they should be obtained, how long surveillance should be continued, and by whom this should be performed. We review the published guidelines for surveillance, available data regarding low- versus high-intensity surveillance plans, current practice patterns, and recommendations for future strategies.

Surgery for constipation in patients with prior spinal cord injury: the Department of Veterans Affairs experience.

OBJECTIVE: Patients with spinal cord injury (SCI) typically have difficulty with constipation. Some undergo surgery for bowel management. We predicted that SCI patients would have higher mortality and/or morbidity rates following such surgery than neurally intact patients receiving the same procedures. We sought to evaluate this using a large population-based data set. METHODS: Patients receiving care at Department of Veterans Affairs Medical Centers (DVAMCs) with computer codes for SCI and constipation who later underwent colectomy, colostomy, or ileostomy during fiscal years 1993-2002 were identified. Charts were requested from the VAMCs where the surgery had been performed and a retrospective chart review of these charts was done. We collected data on patient demographics, six specific pre-operative co-morbidities, surgical complications, and post-operative mortality. Comparisons were made to current literature evaluating a population receiving total abdominal colectomy and ileorectal anastomosis for constipation but not selected for SCI. RESULTS: Of 299 patients identified by computer search, 43 (14%) had codes for SCI and 10 of 43 (24%) met our inclusion criteria. All were symptomatic and had received appropriate medical management. Co-morbid conditions were present in 9 of 10 patients (90%). There were no deaths within 30 days. The complication rate was zero. The mean post-operative length of stay was 17 days. CONCLUSIONS: Patients with SCI comprise about 14% of the population who receive surgery for severe constipation in the Department of Veterans Affairs system. The mortality and morbidity rates in these patients are similar to those reported in other constipated patients who have surgery for intractable constipation. Our data suggest that stoma formation ± bowel resection in patients with SCI is a safe and effective treatment for chronic constipation.

Patient surveillance after initial breast cancer therapy: variation by physician specialty.

BACKGROUND: American Society of Clinical Oncology (ASCO) guidelines recommend only office visits and mammograms as the primary modalities for patient surveillance after treatment for breast carcinoma. This study aimed to quantify differences in posttreatment surveillance among medical oncologists, radiation oncologists, and surgeons. METHODS: We e-mailed a survey to the 3,245 ASCO members who identified themselves as having breast cancer as a major focus of their practices. Questions assessed the frequency of use of 12 specific surveillance modalities for 5 posttreatment years. RESULTS: Of 1,012 total responses, 846 were evaluable: 5% from radiation oncologists, 70% from medical oncologists, and 10% from surgeons; 15% were unspecified. Marked variation in surveillance practices were noted within each specialty and among specialties. CONCLUSION: There are notable variations in surveillance intensity. This suggests overuse or underuse or misuse of scarce medical resources.

Breast cancer in patients with schizophrenia.

BACKGROUND: Schizophrenia has a powerful impact on the outcomes of treatment for physical disorders. This study sought to estimate how the presence of schizophrenia disrupts the course of diagnosis and initial treatment of breast cancer. METHODS: We searched the Patient Treatment File, a comprehensive computer-based system for inpatient data in the Department of Veterans Affairs (DVA) medical system, to identify patients with codes for schizophrenia or schizoaffective disorder who later developed breast cancer. These data were augmented with chart-based clinical data. RESULTS: There were 56 evaluable patients from 34 DVA facilities; 37 (66%) were female. Delay in diagnosis was common. The mean size of the primary tumor was 4 cm in those for whom these data were recorded. Delay in diagnosis was common and many never received the indicated surgery. Distant metastases were present on diagnosis in 12 (21%) and developed after diagnosis in 14 (25%) others, including 7 who inappropriately delayed or refused indicated surgery and 4 who inappropriately delayed or refused indicated neoadjuvant chemotherapy. Twelve verbally abused or physically attacked caregivers. CONCLUSIONS: Patients with schizophrenia who later develop breast cancer often deny they have cancer. They often have high-stage disease at diagnosis and often delay or refuse therapy. Breast-conserving multimodality therapy is often not feasible.

Clonally related methicillin-resistant Staphylococcus aureus isolated from short-finned pilot whales (Globicephala macrorhynchus), human volunteers, and a bayfront cetacean rehabilitation facility.

In May of 2011, a live mass stranding of 26 short-finned pilot whales (Globicephala macrorhynchus) occurred in the lower Florida Keys. Five surviving whales were transferred from the original stranding site to a nearby marine mammal rehabilitation facility where they were constantly attended to by a team of volunteers. Bacteria cultured during the routine clinical care of the whales and necropsy of a deceased whale included methicillin-sensitive and methicillin-resistant Staphylococcus aureus (MSSA and MRSA). In order to investigate potential sources or reservoirs of MSSA and MRSA, samples were obtained from human volunteers, whales, seawater, and sand from multiple sites at the facility, nearby recreational beaches, and a canal. Samples were collected on 3 days. The second collection day was 2 weeks after the first, and the third collection day was 2 months after the last animal was removed from the facility. MRSA and MSSA were isolated on each day from the facility when animals and volunteers were present. MSSA was found at an adjacent beach on all three collection days. Isolates were characterized by utilizing a combination of quantitative real-time PCR to determine the presence of mecA and genes associated with virulence, staphylococcal protein A typing, staphylococcal cassette chromosome mec typing, multilocus sequence typing, and pulsed field gel electrophoresis (PFGE). Using these methods, clonally related MRSA were isolated from multiple environmental locations as well as from humans and animals. Non-identical but genetically similar MSSA and MRSA were also identified from distinct sources within this sample pool. PFGE indicated that the majority of MRSA isolates were clonally related to the prototype human strain USA300. These studies support the notion that S. aureus may be shed into an environment by humans or pilot whales and subsequently colonize or infect exposed new hosts.

Metastatic breast cancer in patients with schizophrenia.

Breast cancer is a major health problem worldwide. The median survival duration for patients with metastatic breast cancer is two to three years. Approximately 1% of populations worldwide have schizophrenia. The manner in which schizophrenic patients fare when diagnosed with metastatic breast carcinoma (MBC) was evaluated. We queried the National Department of Veterans Affairs (DVA) datasets using computer codes for a pre-existing diagnosis of schizophrenia and a later diagnosis of breast carcinoma. Chart-based data concerning the identified subjects were then requested. Previously determined inclusion and exclusion criteria were applied to select evaluable patients from the medical records, prior to extracting demographic details and data concerning the treatment course in each subject. Ten patients had distant metastases at initial diagnosis, while seven developed MBC following prior curative-intent treatment. Two patients refused therapy. Ten did not comply with recommended management. Five harmed or threatened physicians, other caregivers or themselves. Schizophrenic patients with MBC often fail to understand the nature of their illnesses. Often they do not accept palliative treatment, while a number of them do not comply with therapy, once initiated. They often exhibit behaviors that are detrimental to themselves or others. Formal psychiatric consultation is therefore necessary in patients. Several detrimental behaviors may be predicted reliably by history alone.

Surveillance of patients with breast cancer after curative-intent primary treatment: current practice patterns.

PURPOSE: To determine how physicians monitor their patients after initial curative-intent treatment for breast carcinoma. METHODS: A custom-designed survey instrument with four idealized patient vignettes (TNM stages 0 to III) was e-mailed to the 3,245 members of ASCO who had identified themselves as having breast cancer as a major focus of their practice. Respondents were asked how they use 12 specific follow-up modalities during post-treatment years 1 to 5 for each vignette. Mean, median, standard deviation, and range of the intensity of use for each modality were calculated for the four vignettes. RESULTS: Of the 3,245 ASCO members surveyed, 1,012 (31%) responded. Of these, 915 (90%) were evaluable and were included in our analysis. Office visit, mammogram, complete blood count, and liver function tests were the most commonly recommended surveillance modalities. There was marked variation in surveillance intensity. For example, office visit was recommended 4.1 ± 2.2 times (mean ± SD) in year 1 after curative treatment of a patient with stage III breast cancer. Similar variation was observed for all modalities. CONCLUSIONS: The intensity of post-treatment surveillance performed by ASCO members caring for patients with breast cancer varies markedly despite evidence from well-designed, adequately powered randomized controlled trials. Many modalities not recommended by ASCO guidelines are used routinely, which constitutes evidence of overuse. The lack of consensus is likely due to multiple factors and constitutes an appealing target for interventions to rationalize surveillance.

Gastrointestinal cancer surgery in patients with a prior ventriculoperitoneal shunt: the department of veterans affairs experience.

BACKGROUND: The estimated prevalence of hydrocephalus in all age groups is between 1% and 1.5%. Placement of a ventriculoperitoneal (VP) shunt in such patients offers them relatively normal lives. There are minimal data concerning the risk of postoperative complications in patients with shunts who undergo subsequent major visceral operations. We hypothesized that healthy adults who had VP shunts placed for acquired conditions and later underwent surgery for gastric or colon cancer would frequently have dense, shunt-related adhesions and high rates of adverse outcomes, particularly infection. METHODS: We assumed that all veterans were healthy on entry into military service. We searched national Department of Veterans Affairs databases from October 1994 through September 2003 to identify all Department of Veterans Affairs patients with shunts for acquired conditions and a curative-intent operation for stomach or colon cancer. We conducted chart reviews to determine their clinical courses. RESULTS: Five patients had codes for VP shunt, gastric cancer, and gastrectomy; 3 met our inclusion criteria. Fourteen had codes for VP shunt, colon cancer, and colectomy; 4 met our criteria. One of the evaluable gastrectomy patients had dense, shunt-related adhesions. None of the colectomy patients had notable adhesions. There were no postoperative complications in any of the seven patients. CONCLUSION: We believe this is the first report analyzing the clinical course of adults with VP shunts who later had major abdominal cancer surgery. The presence of a shunt was associated with dense adhesions in 1 (14%) of the 7 patients in this series, but not with an increased risk of postoperative complications.

Adjuvant chemotherapy for breast cancer in patients with schizophrenia.

The outcomes of treatment of physical illnesses are strongly affected by the presence of schizophrenia. We aimed to quantify the clinical course of schizophrenic breast cancer patients who were eligible for adjuvant chemotherapy to determine whether patients with this mental illness receive appropriate treatment for this physical illness. We searched the national Department of Veterans Affairs (DVA) computer database using computer codes for schizophrenia to identify patients who later developed breast cancer and were treated in DVA medical centers. Computer-based data were supplemented with chart-based clinical indicators. There were 55 subjects who appeared to be appropriate candidates for adjuvant systemic therapy. A number of these candidates were not offered postoperative endocrine or cytotoxic chemotherapy, while others refused treatment or were non-compliant. Behaviors typical of schizophrenic subjects, including hostility to caregivers, often disrupt their care. Schizophrenic patients often have advanced-stage cancer at diagnosis, often delay diagnosis and are frequently hostile towards healthcare workers. Many of these patients refuse therapy and/or are non-compliant.

Intestinal adenocarcinoma arising in urinary conduits.

It is estimated that >10,000 patients who undergo cystectomy for bladder cancer in the US each year receive a conventional ileal conduit and that >2,000 receive a continent urinary diversion. Case reports of primary intestinal adenocarcinomas in urinary conduits have been published recently, mainly in the urology literature. An epidemic of such cancers in this small, high-risk population seems to be emerging, particularly in conduits that utilize the colon. A case report and literature review was carried out. We describe a patient with a new primary adenocarcinoma arising in a colonic neobladder. We summarize prior literature describing intestinal adenocarcinomas that developed in an intestinal segment used for urinary diversion. Patients with urinary conduits of all types (particularly those utilizing colon rather than ileum) are at high risk of developing a second primary intestinal adenocarcinoma in the conduit. This population is likely to benefit from surveillance measures aimed at detecting such cancers. The primary form of therapy remains adequate surgical resection. General surgeons should be aware of such patients as they may be involved in the diagnosis of, and surgery for, the cancer in the conduit.

Cholecystectomy in patients with prior ventriculoperitoneal shunts.

BACKGROUND: There is little published evidence regarding intraoperative and postoperative complications in patients with ventriculoperitoneal shunts who undergo cholecystectomy. METHODS: Nationwide Department of Veterans Affairs databases were searched to identify patients with International Classification of Diseases, 9th revision, Clinical Modification codes for a VP shunt who later had a cholecystectomy during fiscal years 1994 to 2003. Charts on these patients were obtained and reviewed. RESULTS: Twenty-three patients were deemed evaluable. Of these, 8 had laparoscopic converted to open cholecystectomies. All conversions were owing to dense adhesions. There were 2 cases of postoperative shunt infection that required shunt removal and replacement. CONCLUSIONS: The rate of conversion from laparoscopic to open cholecystectomy was 57% in this study, significantly higher than the reported rate of conversion for patients without shunts in Department of Veterans Affairs Medical Centers (5%). Cholecystectomy in adult patients with a preexisting ventriculoperitoneal shunt appears to result in a shunt infection rate similar to that reported after shunt insertion or revision.

CRSBP-1/LYVE-1 ligands disrupt lymphatic intercellular adhesion by inducing tyrosine phosphorylation and internalization of VE-cadherin.

Cell-surface retention sequence (CRS) binding protein (CRSBP-1) is a membrane glycoprotein identified by its ability to bind PDGF-BB and VEGF-A via their CRS motifs (clusters of basic amino acid residues). CRSBP-1 is identical to LYVE-1 and exhibits dual ligand (CRS-containing proteins and hyaluronic acid) binding activity, suggesting the importance of CRSBP-1 ligands in lymphatic function. Here, we show that CRSBP-1 ligands induce disruption of VE-cadherin-mediated intercellular adhesion and opening of intercellular junctions in lymphatic endothelial cell (LEC) monolayers as determined by immunofluorescence microscopy and Transwell permeability assay. This occurs by interaction with CRSBP-1 in the CRSBP-1-PDGFßR-ß-catenin complex, resulting in tyrosine phosphorylation of the complex, dissociation of ß-catenin and p120-catenin from VE-cadherin, and internalization of VE-cadherin. Pretreatment of LECs with a PDGFßR kinase inhibitor abolishes ligand-stimulated tyrosine phosphorylation of VE-cadherin, halts the ligand-induced disruption of VE-cadherin intercellular adhesion and blocks the ligand-induced opening of intercellular junctions. These CRSBP-1 ligands also induce opening of lymphatic intercellular junctions that respond to PDGFßR kinase inhibitor in wild-type mice (but not in Crsbp1-null mice) as evidenced by increased transit of injected FITC-dextran and induced edema fluid from the interstitial space into lymphatic vessels. These results disclose a novel mechanism involved in the opening of lymphatic intercellular junctions.

Abdominal wall necrosis after harvest of both internal thoracic and inferior epigastric arteries.

BACKGROUND: The internal thoracic artery (ITA) and inferior epigastric artery (IEA) may be used as conduits for myocardial revascularization. Harvesting the ITAs and IEAs can lead to clinically significant ischemia of the anterior abdominal wall. METHODS: We created a registry with data from 108 patients receiving myocardial revascularization with 1 or greater ITA and (or) 1 or greater IEA. After revascularization, patients were followed to document their outcomes during hospitalization. We sought to identify risk factors for tissue necrosis in these patients. RESULTS: All patients had 1 (84%) or 2 (16%) IEAs harvested. Both ITAs were utilized in 81% of patients; 19% had only the left ITA harvested. All patients in whom 2 IEAs were harvested also had 2 ITAs harvested (17 of 108). Of these 17 patients, 2 (12%) developed abdominal wall necrosis. Only patients who had bilateral ITA and bilateral IEA harvest experienced this complication. CONCLUSIONS: Bilateral harvest of ITAs and IEAs results in a moderate risk of clinically significant abdominal wall necrosis. The extent of tissue loss may involve skin, muscle, and fascia, but the peritoneum and posterior rectus sheath remained intact in both affected patients in this series. These data may be most valuable to those who contemplate an abdominal operation in a patient who has had one or more of their ITAs or IEAs taken.