Rice root curling, a response to mechanosensing, is modulated by the rice E3-ubiquitin ligase HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENE1 (OsHOS1).

Plant development depends on the perception of external cues, such as light, gravity, touch, wind or nutrients, among others. Nevertheless, little is known regarding signal transduction pathways integrating these stimuli. Recently, we have reported the involvement of a rice E3-ubiquitin ligase (OsHOS1, HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENE1), previously associated with abiotic stress response, in root responses to mechanical stimuli. We showed that OsHOS1 is involved in the regulation of root curling after mechanosensing and that RNAi::OsHOS1 plants failed to exhibit the root curling phenotype observed in WT. Interestingly, the straight root phenotype of these transgenics correlated with the up-regulation of rice ROOT MEANDER CURLING (OsRMC, a negative regulator of rice root curling) and was reverted by the exogenous application of jasmonic acid. Altogether, our results highlight the role of the proteasome modulating plant responses to mechanical stimuli and suggest that OsHOS1 is a hub integrating environmental and hormonal signaling into plant growth and development.

Should we continue to drain the pylorus in patients undergoing an esophagectomy?

A systematic review of the literature was performed to assess the necessity of a pyloric drainage procedure during an esophagectomy with gastric conduit reconstruction. Earlier data recommend performing a pyloric drainage procedure for all esophagectomies; however, recent studies have questioned this. A thorough literature search (January 2001-November 2011) was performed using the terms esophagectomy, pyloroplasty, pyloromyotomy, botulinum toxin, and pyloric drainage. Only studies that compared patient outcome after undergoing an esophagectomy with a pyloric drainage procedure with those undergoing an esophagectomy without a pyloric drainage procedure were selected. Only four studies, comprising 668 patients in total, were identified that compared patient outcome after undergoing an esophagectomy with or without a pyloric drainage procedure, and two additional meta-analyses were identified and selected for discussion. All studies were retrospective, and because of the heterogeneity of studies, patient demographics, reporting, and statistical analysis of patient outcome, pooling of data and meta-analysis could not be performed. Careful analysis demonstrated that pyloric drainage procedure was associated with a non-significant trend for delayed gastric emptying and biliary reflux, while not affecting the incidence of dumping. No correlation was determined between a pyloric drainage procedure and anastomotic leaks, postoperative pulmonary complications, length of hospital stay, and overall perioperative morbidity. While there are risks associated with a pyloric drainage procedure and data exist supporting its omission during an esophagectomy, no good conclusion can be drawn from the current literature. Larger multi-institutional, prospective studies are required to definitively answer this question.

Extent of lymph node resection does not increase perioperative morbidity and mortality after surgery for stage I lung cancer in the elderly.

BACKGROUND & OBJECTIVES: Pathologic evaluation of > 10 lymph nodes (LNs) is considered necessary for accurate lung cancer staging. However, physicians have concerns about increased risk in perioperative mortality (POM) and morbidity with more extensive LN sampling, particularly in the elderly. In this study, we compared the outcomes in elderly patients with stage I non-small cell lung cancer (NSCLC) undergoing extensive (> 10 nodes) and limited (≤ 10 nodes) LN resections. METHODS: Using data from the Surveillance, Epidemiology and End Results registry linked to Medicare records, we identified 4975 patients ≥ 65 years of age with stage I NSCLC who underwent a lobectomy between 1992 and 2002. Risk of perioperative morbidity and POM after the evaluation of ≤ 10 vs. >10 LNs was compared among patients after adjusting for propensity scores. RESULTS: Multiple regression analysis showed similar POM between the two groups (OR, 1,01; 95% CI, 0,71-1,44). Other postoperative complications were similar across groups except for thromboembolic events, which were more common among patients undergoing resection of > 10 LNs (OR, 1,72; 95% CI, 1,12-2,63). CONCLUSIONS: These data suggest that evaluation of > 10 LNs, which allows for more accurate staging, appears to be safe in the elderly patients undergoing lobectomy for stage I NSCLC without compromising postoperative recovery.

Influence of race on kidney transplantation in the Department of Defense healthcare system.

BACKGROUND: We report the influence of race on transplant outcomes in the Department of Defense (DOD) system. METHODS: Retrospective cohort analysis of all kidney transplants performed at WRAMC from 1996 to 2005. Kaplan-Meier analysis was used to assess for differences in graft survival, and Cox regression was used to calculate adjusted hazard ratios for graft loss. For our analyses, we used the cutoff of 6 years (year 2000) when we introduced thymoglobulin induction; maintenance immunosuppression consisted of mycophenolate mofetil and tacrolimus, and rapid steroid taper (completed withdrawal at 6 weeks) was used for all patients. RESULTS: There were 220 transplants (91 Blacks, 107 Caucasians and 22 Asians). Because the curve for graft survival for Blacks over time violated the proportional hazards assumption (at 6 years post-transplant), analysis was segregated into two segments. Through 6 years of follow-up, graft survival was 77% for Blacks and 81% for non-Blacks (p = 0.74 by log rank). Through 9 potential years of follow-up, graft survival for Blacks was 56% and 78% for Whites (p = 0.005). In Cox regression analysis, Black race, compared with non-Black race, was not significantly associated with graft loss at 6 years, but was significantly associated with graft loss occurring after 6 years. CONCLUSIONS: In the DOD health system, no significant differences were seen in graft survival among recipients of different races at 6 years. Black recipients who received a kidney transplant before the year 2000 showed decreased graft survival compared to non-Blacks. This was consistent with change in immunosuppressive regimen in our institution with the introduction of thymoglobulin induction and maintenance therapy with tacrolimus, mycophenolate mofetil and withdrawal of prednisone at 6 weeks.

Acute renal allograft rejection following pegylated IFN-alpha treatment for chronic HCV in a repeat allograft recipient on hemodialysis: a case report.

Interferon alpha (IFN-alpha) can be effective therapy for patients with chronic kidney disease who have chronic hepatitis C (HCV). However, acute allograft rejection has been reported in association with IFN-alpha following kidney transplantation, and therefore IFN therapy is recommended prior to, rather than after, kidney transplantation whenever feasible. The special case of repeat allograft recipients who contract HCV after the first transplantation presents special difficulties. This report features the case of a repeat allograft recipient who presented with neutropenic fevers after 5 months of pegylated IFN-alpha therapy, initiated 6 months following the functional loss of his third graft and the reinitiation of hemodialysis (HD). Physical exam, radiographic and laboratory findings led to allograft nephrectomy. The pathologic findings supported a diagnosis of acute-on-chronic rejection. This represents a rare case of IFN-alpha induced rejection following allograft failure and return to HD in a repeat allograft recipient. It also calls attention to the need for a high index of suspicion for the development of allograft rejection, which may require allograft nephrectomy even after allograft 'failure'.

Characterization of an immune response.

The characterization of any detected antibodies provides detailed information that can be critical to understanding the significance of an immune response. The BIAcore immunoassay provides a straightforward means of characterizing many aspects of the immune response including antibody concentration, specificity, binding affinity, and the presence of isotypes. One important aspect of the immune response is determination of neutralizing capability, which requires a biological assay. The ultimate clinical significance of an immune response can only be fully understood when data from antibody characterization are coupled with clinical data from the patient. Some of the factors that can contribute to the clinical significance of an immune response are: (i) magnitude of the immune response (concentration of antibodies detected); (ii) duration of the immune response (continuous antibody production or sporadic and not sustained); (iii) correlation with any adverse events; (iv) correlation with a change in pharmacokinetics (either mediating sustained circulation or enhanced clearance of the drug); (v) biological neutralization of the drug; (vi) biological neutralization of an endogenous protein. Full characterization of the immune response requires the incorporation of antibody assays, pharmacokinetic assays, and clinical data.

Use of preoperative functional neuroimaging to predict language deficits from epilepsy surgery.

BACKGROUND: Left anterior temporal lobectomy (L-ATL) may be complicated by confrontation naming deficits. OBJECTIVE: To determine whether preoperative fMRI predicts such deficits in patients with epilepsy undergoing L-ATL. METHODS: Twenty-four patients with L-ATL underwent preoperative language mapping with fMRI, preoperative intracarotid amobarbital (Wada) testing for language dominance, and pre- and postoperative neuropsychological testing. fMRI laterality indexes (LIs), reflecting the interhemispheric difference between activated volumes in left and right homologous regions of interest, were calculated for each patient. Relationships between the fMRI LI, Wada language dominance, and naming outcome were examined. RESULTS: Both the fMRI LI (p < 0.001) and the Wada test (p < 0.05) were predictive of naming outcome. fMRI showed 100% sensitivity and 73% specificity in predicting significant naming decline. Both fMRI and the Wada test were more predictive than age at seizure onset or preoperative naming performance. CONCLUSIONS: Preoperative fMRI predicted naming decline in patients undergoing left anterior temporal lobectomy surgery.

New technologies for the detection of antibodies to therapeutic proteins.

The determination of antibody formation in response to a therapeutic product requires that a variety of data be evaluated. In addition to examining immuno-assay and bioassay results, it is important to determine any clinical relevance. By also examining pharmacokinetic data as well as other clinical results, an evaluation can be made as to whether any clinically relevant antibodies were generated. To help in this evaluation, it is important to fully characterize the antibodies that are generated. Both the BIAcore and IGEN platforms are powerful tools for determining if antibodies have been produced in a subject The BIAcore is also able to characterize these antibodies as to isotype, relative concentration, and relative affinity. The bioassay result can identify serum samples that contain an agent capable of inhibiting a biological effect of a drug. When combined with the results of an immuno-assay, it is possible to determine if the antibodies are capable of neutralizing the drug.

Impact of HIV seropositivity on graft and patient survival after cadaveric renal transplantation in the United States in the pre highly active antiretroviral therapy (HAART) era: an historical cohort analysis of the United States Renal Data System.

BACKGROUND: National statistics are presented for patient survival and graft survival in patients seropositive for the human immunodeficiency virus (HIV+) at the time of renal transplantation in the era prior to highly active antiretroviral therapy (HAART). METHODS: Historical cohort analysis of 63, 210 cadaveric solitary renal transplant recipients with valid HIV serology entries in the United States Renal Data System (USRDS) from 1 January 1987 to 30 June 1997. The medical evidence form was also used for additional variables but, because of fewer available values, was analyzed in a separate model. Outcomes were patient characteristics and survival associated with HIV+ status. RESULTS: Thirty-two patients (0.05%) in the study period were HIV+ at transplant. HIV+ patients were comparable to the national renal transplant population in terms of gender and ethnic distribution but were younger and had younger donors and better HLA matching than the USRDS population. Patient and graft three-year survival were significantly reduced in HIV+ recipients (53% graft, 83% patient survival) relative to the USRDS population (73% and 88%, respectively). In multivariate analysis, HIV+ status was independently associated with patient mortality and decreased graft survival in recipients of cadaveric kidney transplants. CONCLUSIONS: This analysis was retrospective and may underestimate the number of HIV+ patients transplanted in the United States. Although the clinical details of patient selection for transplant were unknown, these results show HIV+ patients can have successful outcomes after cadaveric renal transplantation, although outcomes are significantly different from HIV- recipients.

Use of biosensors to monitor the immune response.

Biosensor instruments, such as the BIACORE, are gaining popularity for analysing serum samples for the presence of antibodies. These instruments offer several advantages in the detection and subsequent characterization of clinically relevant antibodies generated in response to administration of therapeutic proteins. Much like other common immunoassay platforms, immobilized ligand is used to capture antibodies. Unlike conventional approaches, the ligand is immobilized to the surface of a biosensor chip, with detection based upon surface plasmon resonance. This assay platform, therefore, does not require reporter molecules such as enzymes, fluorochromes or radioisotopes that are common to conventional immunoassay methodologies. Additional desirable features of the biosensor platform include real-time detection of the binding of antibody to ligand (for kinetic measurements) as well as straightforward characterization of antibody isotype, specificity and relative concentration. This is all performed with minimum serum requirements (typically 10 microlitres per sample analysed) in a fully automated environment. The unique features of the biosensor instrument warrant that these assays are referred to as biosensor immunoassays to clearly distinguish them from more conventional immunoassay methodologies, such as ELISA.

Esophagectomy for esophageal cancer.

This review considers the esophagectomy techniques in the treatment of esophageal cancer and provides the guidelines for optimizing the patients' chances at cure, minimizing the risk of mediastinal enteric leak (which carries a mortality rate as high as 50%) and minimizing associated pulmonary insufficiency and infection. The 4 most commonly used routes for resection and replacement include a transhiatal, transthoracic (Ivor-Lewis), tri-incisional (right chest then simultaneous abdominal and left neck), and left chest (distal tumors). Each of these techniques will be described as will the use of colon and jejunum for esophageal replacement. The healthy stomach is the preferred conduit for esophageal replacement. The stomach is well vascularized, easily reaches to the neck, and requires only a single anastomosis for re-establishing intestinal continuity. When the stomach is not available (usually because of prior surgery or disease) the choice of conduits include colon and jejunum. With respect to minimally invasive esophagectomy for esophageal cancer, several groups have significant experience with this and report excellent results. This is an evolving technique but holds much promise for improving the quality of life of patients with cancer without compromising their survival. In locally advanced middle third tumors, thoracotomy and dissection under direct vision's desirable and improves the safety of the operation. The same may apply to tumors receiving neoadjuvant therapy. For tumors of the distal esophagus, transhiatal, tri-incisional, and Ivor-Lewis resection are probably equally as safe, and appear to result in equivalent long-term survival. An intrathoracic anastomotic leak is disastrous, carrying a mortality rate of up to 50%. Any surgeon who performs esophagectomy with an intrathoracic anastomosis must do so with a low incidence of leakage, certainly under 5%. Consideration should be given to a cervical placement if there are factors increasing the risk such as the use of induction therapy.

Spatial variation of plasma flow in the oxazolone-stimulated microcirculation.

INTRODUCTION: In cutaneous lymphocytic inflammation, enhanced regional blood flow is suggested by persistent erythema and warmth. Direct assessment of the microcirculation, however, has been limited by tissue edema and skin thickness. METHODS: To assess the microcirculatory adaptations to the epicutaneous antigen oxazolone, we studied the first pass kinetics and microvascular topography of the inflammatory skin microcirculation using a specially adapted epi-illumination intravital microscopy system. The fluorescence intravital videomicroscopy and streaming image acquisition of fluorescein-labeled dextran (approximately 500,000 MW) injections were used to assess changes in plasma flow. RESULTS: Direct plasma tracer injections of both the oxazolone-stimulated and control microcirculation demonstrated comparable transit times (leading edge and intensity-weighted peak times) from the carotid artery to the superficial vascular plexus (p > 0.05). In contrast to transit times, continuous infusion of the plasma tracer demonstrated a significant increase in the delivery of the fluorescein-labeled dextran to the oxazolone-stimulated microcirculation. Quantitative morphometry of intravital microscopic images demonstrated a 2.2-fold increase in the mean diameter of vessels in the superficial vascular plexus (p < 0.01). Further, fluorescence intensity mapping indicated that the increase was associated with increased perfusion of focal regions of the superficial vascular plexus (p < 0.001). CONCLUSIONS: These results indicate that the oxazolone-stimulated adaptations of the inflammatory microcirculation include both microvascular dilatation and the redistribution of plasma flow.

Chemotherapy for a patient with advanced non-small-cell lung cancer during pregnancy: a case report and a review of chemotherapy treatment during pregnancy.

BACKGROUND: Lung cancer is the most common cause of cancer death in women in the USA. Lung cancer arising during pregnancy is rare and has been reported only 15 times since the 1950s. However, the use of chemotherapy for lung cancer during pregnancy has not previously been reported. METHODS: The history, treatment and outcome of a patient with stage IV non-small-cell lung carcinoma (NSCLC) diagnosed during pregnancy is presented. Previous published reports on lung cancer were retrieved by a literature search of Medline and Cancerlit. RESULTS: A 31-year-old woman was diagnosed as having stage IV NSCLC with bilateral pulmonary involvement when 26 weeks pregnant. Her shortness of breath progressed to dyspnea at rest on 100% inspired oxygen. Therefore, she was treated with systemic chemotherapy using cisplatin and vinorelbine. Despite this treatment, her oxygenation declined further over the next 4 days and thus the baby was delivered via cesarean section after 27 weeks of gestation. Four cycles of vinorelbine and cisplatin have now been administered. Following this treatment, the patient has experienced a significant clinical improvement and no longer requires supplemental oxygen. No chemotherapy-related adverse effects have been noted in the baby. In the 15 previously reported patients with concurrent lung cancer and pregnancy, chemotherapy administration during pregnancy has not been described. CONCLUSIONS: Treatment of lung cancer with chemotherapy during pregnancy should be considered on an individual basis with regard to the stage of the cancer and the maturity of the fetus. To our knowledge, the case presented here is the first report of a woman receiving chemotherapy for lung cancer while pregnant.

Biphasic response of the regional lymphatics in the normal lymphocyte transfer reaction.

BACKGROUND: Initially developed for histocompatibility testing, the normal lymphocyte transfer (NLT) reaction involves the intradermal injection of allogeneic lymphocytes from one individual to another. Because of the unique kinetics of the immunological response to allogeneic lymphocytes, the NLT reaction has been considered an informative system for the analysis of transplant immunity. METHODS: In this study, we used bilateral efferent lymph duct cannulations in sheep to examine the regional lymphatic response to the NLT reaction. Our studies used monoclonal antibodies to define lymphocyte population dynamics and DNA flow cytometry to reflect lymphocyte proliferative responses. RESULTS: The results confirmed a biphasic NLT reaction. An unexpected finding was the marked differences between the early and late NLT responses. The early response was characterized by T-lymphocyte proliferation, as reflected by S-phase DNA, which was comparable in both the NLT-stimulated and contralateral control efferent lymphocytes. This bilateral proliferative response was observed in both CD4+ and CD8+ lymphocytes. In contrast, the late response was restricted to the efferent lymph from the NLT-stimulated lymph node. Dual-parameter flow cytometry demonstrated that the dominant component of this unilateral NLT response was CD8+ lymphocytes. CONCLUSIONS: These results suggest important functional distinctions between systemic and regional lymphatic responses to intradermal alloantigens.

Combined antegrade and retrograde dilation: a new endoscopic technique in the management of complex esophageal obstruction.

BACKGROUND: Esophageal strictures that cause complete obstruction are often difficult to dilate with standard bougienage techniques. METHODS: A new technique was developed and applied, combined antegrade and retrograde dilation, for dilatation of complex esophageal strictures. The stomach is accessed and an endoscope (9.8 mm diameter) is directed under fluoroscopy in a retrograde fashion into the distal esophagus. A guidewire with a hydrophilic coating is advanced through the stricture and then pulled through the mouth with a simultaneously placed proximal endoscope. The guidewire is then used as a guide for antegrade esophageal dilatation. RESULTS: Ten patients with complex esophageal strictures (with and without fistulas) were treated with this technique. Three required a second combined antegrade and retrograde dilation procedure. All strictures were dilated and no perforations occurred. CONCLUSIONS: Combined antegrade and retrograde dilation is a safe and effective technique for dilation of complex obstructing esophageal lesions.

Magnetic resonance analysis of postsurgical temporal lobectomy.

BACKGROUND AND PURPOSE: The effect of temporal lobe transection area, volume of postoperative gliosis, and surgical technique on patients' seizure-free outcome is unknown. The authors studied the effects of these variables on patients' seizure-free outcome. METHODS: A retrospective review of magnetic resonance imaging examinations acquired 3 to 18 months after temporal lobe resection was carried out for 18 patients with intractable temporal lobe seizures and known postsurgical outcomes for more than 2 years. The total volume of radiologically probable gliosis evident on axial proton-density-weighted images was calculated for each patient using software on an independent console. The total area of temporal lobe surface transected by the scalpel was calculated as well, using sagittal T1-weighted images. The total volume of gliosis, the total area of transected temporal lobe, and the specific type of surgery (sparing vs no sparing of the superior temporal gyrus) were then correlated with the postsurgical outcome of the patients. An examiner with no prior knowledge of the patients' postsurgical outcomes carried out the above calculations and measurements. The patients' postoperative outcome was defined using Engel classifications, and patients were divided into 2 groups: group A with Engel class 1 (n = 9) and group B with Engel classes 2-4 (n = 9). RESULTS: The mean volumes of postoperative gliosis were not significantly different between group A (3592.3 mm3) and group B (4270 mm3). The mean area of transected temporal lobe was also similar between group A (1865.2 mm2) and group B (1930 mm2). With regard to surgical technique, there were 5 patients who had the superior temporal gyrus resected and 13 who did not. Eighty percent of patients with the superior temporal gyrus resected were Engel class 1 or 2, whereas only 20% were of Engel class 3 or 4. CONCLUSIONS: The authors found no clear association between postoperative outcome and residual temporal lobe gliosis, the surgical technique, or the total area of temporal lobe transected by the scalpel.

Bronchoscopic volume reduction: a safe and effective alternative to surgical therapy for emphysema.

Lung volume reduction surgery (LVRS), the removal of damaged, hyperexpanded lung, has been shown to improve respiratory function in many patients with end-stage emphysema. We report the results of an animal study using a new transbronchoscopic alternative to LVRS in which a washout solution and fibrin-based glue are used to collapse, seal, and scar target regions of abnormal lung. Twelve sheep had static and dynamic lung functions measured at baseline. Emphysema was produced by inhaled papain (7,000 U/wk x 4 wk), resulting in a significant increase of lung volumes, compliance, and airway resistance. The animals were then divided into three treatment groups of four animals, and underwent surgical volume reduction (SVR), bronchoscopic volume reduction (BVR), or bronchoscopy alone (Sham-BVR). Response to each intervention was assessed 8 to 12 wk after treatment by measuring lung function and examining lung tissue. BVR and SVR groups responded with significant and similar decreases in TLC and residual volume (RV). Tissue examination demonstrated that BVR caused collapse of the lung with focal scarring in 11 of 20 target territories (55% success rate). Three of the 11 target zones developed sterile abscesses. Postprocedure complications were less frequent with BVR than with SVR. This pilot study suggests that lung volume reduction can be achieved in animals without surgery using a bronchoscopic approach and a novel fibrin-based glue system. BVR has the potential for simplifying volume reduction, extending indications, and reducing morbidity, mortality, and costs in humans.

Cell adhesion molecule expression in the sheep thymus.

Cell adhesion molecules are potential regulating factors in both prethymic and intrathymic T cell development. An experimental challenge has been the development of a large animal model that facilitates in vivo studies of both intrathymic development and lymphocyte migration. To extend earlier studies of thymic development, we have developed a panel of monoclonal antibodies (mAb) to a variety of sheep cell adhesion molecules. Immunohistochemistry was used to define mAb reactivity and flow cytometry was used to quantify expression of cell adhesion molecules within the thymus. To facilitate flow cytometry definition of cortical thymocytes, mAbs were developed to the sheep CD1 antigen. Dual parameter flow cytometry provided a phenotypic characterization of cell adhesion molecule expression on both CD1(+) and CD1(-) sheep thymocyte populations. These studies demonstrated significantly enhanced cortical thymocyte expression of three cell adhesion molecules: beta1 integrin (CD29), ICAM-2 and LFA-3. The beta1 integrin cell adhesion molecule was also expressed at higher levels on CD1(+) thymocytes in post-natal lambs as compared to adult sheep. These studies of thymocyte membrane molecule expression should facilitate future investigations of sheep intrathymic development and T lymphocyte immigration.