Th17 and non-Th17 interleukin-17-expressing cells in chronic lymphocytic leukemia: delineation, distribution, and clinical relevance

Background

The levels and clinical relevance of Th17 cells and other interleukin-17-producing cells have not been analyzed in chronic lymphocytic leukemia. The objective of this study was to quantify blood and tissue levels of Th17 and other interleukin-17-producing cells in patients with this disease and correlate blood levels with clinical outcome.

Design and Methods

Intracellular interleukin-17A was assessed in blood and splenic mononuclear cells from patients with chronic lymphocytic leukemia and healthy subjects using flow cytometry. Interleukin-17A-producing cells were analyzed in formalin-fixed, paraffin-embedded spleen and lymph node sections using immunohistochemistry and immunofluorescence.

Results

The absolute numbers of Th17 cells in peripheral blood mononuclear cells and the percentages of Th17 cells in spleen cell suspensions were higher in patients with chronic lymphocytic leukemia than in healthy subjects; in six out of eight paired chronic lymphocytic leukemia blood and spleen sample comparisons, Th17 cells were enriched in spleen suspensions. Circulating Th17 levels correlated with better prognostic markers and longer overall survival of the patients. Two “non-Th17” interleukin-17-expressing cells were identified in chronic lymphocytic leukemia spleens: proliferating cells of the granulocytic lineage and mature mast cells. Granulocytes and mast cells in normal spleens did not express interleukin-17. Conversely, both chronic lymphocytic leukemia and healthy lymph nodes contained similar numbers of interleukin-17+ mast cells as well as Th17 cells.

Conclusions

Th17 cells are elevated in chronic lymphocytic leukemia patients with better prognostic markers and correlate with longer survival. Furthermore, non-Th17 interleukin-17A-expressing cells exist in chronic lymphocytic leukemia spleens as maturing granulocytes and mature mast cells, suggesting that the microenvironmental milieu in leukemic spleens promotes the recruitment and/or expansion of Th17 and other IL-17-expressing cells. The pathophysiology of Th17 and non-Th17-interleukin-producing cells in chronic lymphocytic leukemia and their distributions and roles in this disease merit further study.     

Central airway obstruction due to malignant fibrous histiocytoma metastasis in a case with Mounier-Kuhn syndrome

Malign fibrous histiocytoma is one of the most observed soft tissue sarcomas seen in the adults. The most common metastasis region is the lung and metastasis. Mounier-Kuhn syndrome is characterized by the highly dilatation of the trachea and bronchi. We may encounter with the major airway obstruction in the endoluminal or extraluminal lung and mediastinal masses or those with both components together. In this article, we would like to highlight the occurrence of a rare seen clinical situation secondary to the giant mediastinal malign fibrous histiocytoma metastasis and the clinical difficulties experienced in resolving of the main airway obstruction caused by the mass. Since the lack of the similar studies conducted previously, we found the case worth presenting.     

Early-mid term follow-up results of percutaneous closure of the interatrial septal defects with occlutech figulla devices: a single center experience

Background: Percutaneous closure of secundum type atrial septal defect (ASD) and patent foramen ovale (PFO) has gained widespread use in recent years. Herein, we evaluated the safety and efficacy of the Occlutech® Figulla devices for PFO and ASD closure in a reference tertiary center. Methods: All 143 patients (46.9% male, mean age 39.3 ± 12.2 years) who underwent transcatheter PFO (n = 85) and ASD (n = 58) closure with Occlutech® Figulla devices between February 2009 and October 2011 were included in this study. An echocardiographic follow‐up examination was performed at the 1st, 6th, and 12th month visits. Results: The devices were successfully implanted in all 143 patients (100%). In‐hospital periprocedural complications were device embolization (0.7%; 1 ASD patient), atrial fibrillation (1.4%; 1 ASD and 1 PFO patients), supraventricular tachycardia (0.7%; 1 PFO patient), and vascular access hematoma (0.7%; 1 ASD patient). Among ASD patients, 2 patients had trivial (jet width <1 mm in diameter) and 1 patient had small (1–2 mm) residual shunts before hospital discharge, which disappeared after the 6‐month visit. During the mean 15.4 ± 9.6 months follow‐up, all patients were asymptomatic and no ischemic stroke, cardiac perforation, device erosion, embolization, thrombus formation, or malposition of the device was observed. Conclusions: Percutaneous PFO and secundum type ASD closure with the novel Occlutech® Figulla Occluder devices without left atrial central pin and with significantly reduced meshwork was safe, feasible, and effective. (J Interven Cardiol 2012;25:375–381)     

Resterilized Mesh in Repair of Abdominal Wall Defects in Rats

A variety of negative opinions about repeated usage of relatively expensive resterilized synthetic meshes have been considered. It had been stated that resterilized polypropylene meshes inhibits fibroblastic activity, decreases proliferative activity, and increases apoptosis in human fibroblast culture, in vitro. The purpose of this study is the in vivo evaluation of the resterilized mesh repairs of abdominal hernia defects in rat models of incisional hernia by comparing primer repair and original mesh repairs. The rats (n = 22) were separated into three groups. While the abdominal defect was repaired by primary suture in the control group (CG), the defects were repaired by original mesh (OG) or resterilized mesh (RG) in mesh-repaired groups. After 21 days, the rats were evaluated for tissue tensile strengths, tissue hydroxyproline levels, tissue inflammation, fibrosis, and apoptosis. Although the tensile strengths in OG and RG were significantly higher than those of CG (p <. 05 and p <. 05), there was no significant difference between two groups. The tissue hydroxyproline levels in OG and RG were also higher than those of CG. The difference was not significant between the two groups. The inflammation and fibrosis indexes in OG and RG were significantly higher than those of CG (p <. 0001 for both), but there was no difference between groups. While the apoptosis index in OG and RG was also higher than that of CG (p <. 0001 for both), there was no significant difference between OG and RG. The usage of resterilized mesh in abdominal wall repair did not reduce the tissue tensile strength, did not affect the tissue hydroxyproline levels, did not decrease the fibrosis, and did not increase the tissue inflammation and apoptosis. In conclusion, usage of resterilized meshes in abdominal wall defects was as safe as sterilized meshes.     

The Effects of Hyperbaric Oxygen Therapy on Colonic Anastomosis in Rats With Peritonitis

The aim of this study is to investigate the healing effect of hyperbaric oxygen (HBO) on colonic anastomoses in the presence of experimentally induced peritonitis. Thirty-two rats were allocated randomly into short-term anastomosis (STA), short-term anastomosis + HBO treatment (STA+HBO), long-term anastomosis (LTA), and long-term anastomosis + HBO (LTA+HBO) treatment groups. The STA and LTA groups were administered fluid resuscitation and antibiotics for 3 and 7 days, respectively, whereas the HBO treatment groups received additional HBO therapy for 3 and 7 days, respectively. The rats were reoperated on the third and the seventh days of anostomoses for evaluation. The bursting pressures in STA+HBO and LTA+HBO therapy groups were significantly higher than those in groups with anastomoses alone (p <. 001 and p <. 01). HBO therapy did not affect the fibrotic index neither in STA nor in LTA groups (p >. 05 for both); however, it was significantly higher in LTA+HBO group than that in STA+HBO group (p <. 05). The hydroxyproline level was significantly higher in LTA group than in STA group (p <. 05), yet HBO therapy did not affect the hydroxyproline levels in STA or LTA groups (p >. 05 for both). It is concluded that hyperbaric oxygen treatment has positive effects on colonic anastomotic healing in case of peritonitis.     

A platinum blue complex exerts its cytotoxic activity via DNA damage and induces apoptosis in cancer cells

Here, we describe the characteristics of a Pt‐blue complex [Pt₄(2‐atp)₈(H₂O)(OH)] (2‐atp: 2‐aminothiophenol) as a prodrug for its DNA‐binding properties and its use in cancer therapy. The nature of the interaction between the Pt‐blue complex and DNA was evaluated based on spectroscopic measurements, the electronic absorption spectra, thermal behavior, viscosity, fluorometric titration, and agarose gel electrophoresis. Our results suggested that the compound was able to partially intercalate DNA and appeared to induce both single‐ and double‐stranded breaks (DBS) on DNA in vitro, but no DSBs in cells. The ability of the compound to induce DNA damage was dependent on reactive oxygen species (ROS) in vitro. There was also elevated formation of ROS and SOD expression in response to drug treatment in cell culture. The complex was found to be more cytotoxic to cancer cells in comparison with noncancer controls using WST‐1 assay. The mean of cell death was determined to be apoptosis as assessed via biochemical, morphological, and molecular observations, including DNA condensation/fragmentation analysis, live cell imaging microscopy, TUNEL analyses, and increase in the levels of pro‐apoptotic genes such as Bag3, Bak, Bik, Bmf, and Hrk. Hence, the Pt‐blue complex under study grants premise for further studies.