Sézary syndrome treated with narrowband ultraviolet B: time-course measurement of serum levels of CCL17/CCL27

We describe a patient with Sézary syndrome (SS) who was successfully treated with topical steroid and narrowband UVB. Sézary cells in peripheral blood correlated with severity of skin lesions. In addition, serum levels of CCL17 and CCL27 decreased as disease activity improved. These chemokines may be important for the pathogenesis of SS.     

Stenting of Ductus Arteriosus in a Neonate with Truncus Arteriosus and Interrupted Aortic Arch Associated with a Right Aortic Arch

This report describes a case in which successful stenting of ductus arteriosus (DA) was performed for a 27-day-old boy with truncus arteriosus (TA) and interrupted aortic arch (IAA). The patent DA was associated with a right aortic arch. During the balloon catheter crossing of the ductus, the DA and descending aorta shifted toward the left side, making appropriate stent placement difficult. Additionally, the DA was longer than in previously reported cases with left aortic arch, thus requiring a longer stent. This experience suggests that DA stenting in neonates with TA and IAA averts surgical repair during the early neonatal period.     

Phase II study of a salvage regimen using cyclophosphamide, high-dose cytarabine, dexamethasone, etoposide, and rituximab in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma

The management of relapsed or refractory B-cell non-Hodgkin's lymphoma (B-NHL) remains challenging. We investigated the efficacy and safety of salvage chemoimmunotherapy (CHASER) in patients with relapsed or refractory B-NHL who had radiographically measurable disease and adequate major organ function. The CHASER treatment consisted of: rituximab 375 mg/m², day 1; cyclophosphamide 1200 mg/m², day 3; cytarabine 2 g/m², days 4 and 5; etoposide 100 mg/m², days 3–5; and dexamethasone 40 mg, days 3–5. The treatment was repeated every 3 weeks up to a total of four courses in the absence of disease progression. Thirty-two patients were enrolled and received a median of four courses of treatment (range 1–4 courses) per patient. Twenty patients (63%) were previously treated with rituximab-containing regimens. The median age was 54 years (range 28–67 years). The treatment was generally well tolerated, with major toxicities being grade 4 neutropenia ( n  = 32), thrombocytopenia requiring transfusion ( n  = 28), and grade 3 transaminase elevation ( n  = 2). Overall response rates in the entire group, and in patients with indolent ( n  = 17) and aggressive ( n  = 15) diseases were 84%, 100% and 67%, respectively. Responses were observed similarly in patients with ( n  = 20) and without ( n  = 12) previous rituximab exposure (85% and 83%, respectively). Stem cell harvest was successful in 19 of 22 patients. The median time to treatment failure for the entire group was 24.5 months. This promising result of high activity and favorable toxicity profile warrants further investigation in large-scale multicenter trials. ( Cancer Sci 2008; 99: 179–184)     

Expression of Tyk2 in dendritic cells is required for IL-12, IL-23, and IFN-gamma production and the induction of Th1 cell differentiation

It is well documented that dendritic cells (DCs), representative antigen-presenting cells, are important sources of Th1-promoting cytokines and are actively involved in the regulation of T-helper-cell differentiation. However, the intracellular event that regulates this process is still largely unknown. In this study, we examined the role of Tyk2, a JAK kinase that is involved in the signaling pathway under IL-12 and IL-23, in DC functions. While the differentiation and maturation of DCs was normal in Tyk2-deficient (Tyk2(-/-)) mice, IL-12-induced Stat4 phosphorylation was diminished in Tyk2(-/-) DCs. IL-12-induced IFN-gamma production was also significantly diminished in Tyk2(-/-) DCs to levels similar to those in Stat4(-/-) DCs. Interestingly, Tyk2(-/-) DCs were defective in IL-12 and IL-23 production upon stimulation with CpG ODN. Furthermore, Tyk2(-/-) DCs were impaired in their ability to induce Th1-cell differentiation but not Th2-cell differentiation. Taken together, these results indicate that the expression of Tyk2 in DCs is crucial for the production of Th1-promoting cytokines such as IL-12 and IFN-gamma from DCs and thereby for the induction of antigen-specific Th1-cell differentiation.     

Distraction osteogenesis assisted by tissue engineering in an irradiated mandible: a case report

Distraction osteogenesis (DO) can provide predictable bone regeneration without grafting procedures but requires long treatment time and forms less bone transverse to the direction of distraction. To promote 3-dimensional bone formation and shorten the consolidation period, tissue-engineered osteogenic material (injectable bone) was applied in a patient who was being treated with vertical DO with an osteocutaneous fibular flap to reconstruct the mandible. The material, which comprised autologous mesenchymal stem cells culture-expanded then induced to be osteogenic in character and platelet-rich plasma (PRP) activated with thrombin and calcium chloride, was infiltrated into the distracted tissue at the end of distraction and injected into a space created labially with a titanium mesh at implant placement. The infiltration contributed to full consolidation of the regenerate for 3 months, and the injection thickened the regenerated ridge and bridged a gap between the native mandible and distracted fibula. The reconstructed mandible was expanded from 10 mm to 25 mm in height despite a lacerated and opened labial periosteum in the distracted area. Six implants 18 mm in length were placed and subsequently achieved osseointegration. The cutaneous flap covering the implants was trimmed, and the palatal mucosa was transplanted to the regenerated ridge for vestibuloplasty. These raw surfaces were covered with PRP; within 3 weeks, they had attained an epithelium. The implants have supported a fixed prosthesis with adequate surrounding bone and attached mucosa. DO was assisted by tissue engineering and became effective in restoring the compromised mandible.     

Angiotensin II activates intermediate-conductance Ca2+ -activated K+ channels in arterial smooth muscle cells

Angiostensin II (Ang II) regulates the migration and proliferation of vascular smooth muscle cells. Recent studies indicate that intermediate-conductance Ca2+ -activated K+ (IKca) channels have an important role in cell migration and proliferation. It is not known, however, whether the action of Ang II is linked to IKca channel regulation. Here, we investigated the modulation of IKca channels by Ang II in artery smooth muscle cells. Functional IKca channel expression in cultured embryonic rat aorta smooth muscle (A10) cells was studied using the patch-clamp technique. These cells predominantly express IKca channels. In contrast, large-conductance Ca2+ -activated K+ (BKca) currents were rarely observed in excised patches. Ang II increased the IKca current in a contration-dependent manner. Losartan (1.0 microM), an AT1 selective antagonist, abolished the activation of IKca channels by Ang II. Pretreatment with 100 microM myristoylated protein kinase C inhibitor peptide 20-28 or 10 microM GF109203X completely abolished the AngII-induced activation of IKca currents, whereas the action of Ang II was not prevented in the presence of 100 microM Rp-cyclic 3', 5'-hydrogen phosphotiate adenosine triethylammonium, a protein kinase A inhibitor, or 1.0 microM KT-5823, a protein kinase G inhibitor. A membrane permeant analogue of diacylglycerol 1, 2-dioctanoyl-sn-glycerol (10 microM) induced the activation of IKca currents. These data suggest that Ang II activates IKca channels through the activation of protein kinase C, and the AT1 receptor is involved in the regulation of these channels.