Prolonged lymphocytopenia after bendamustine therapy in patients with relapsed or refractory indolent B-cell and mantle cell lymphoma.

This corrects the article DOI: 10.1038/bcj.2015.86.

Factors related to long-term prognosis in medically treated type B aortic dissection: a physical predisposing factor.

AIM: In medically treated patients with Stanford type B aortic dissection, it has been shown that the state of the dissecting aorta in the acute phase predicts the prognosis. The present study examined other crucial factors, including physical characteristics, related to the long-term prognosis in type B aortic dissection. METHODS: Two hundred and two patients with type B aortic dissection who were discharged alive with medical treatment in the acute phase (mean age 66.5 years, range 29-90 years, 160 males) were followed. RESULTS: During the mean follow-up period of 4.9 years (ranging up to 12.2 years), 37 all-cause deaths were confirmed. A surgical procedure related to aortic dissection was performed in 8, and re-dissection occurred in 3. The survival rate at 5 years after onset was 82%. On Cox regression analysis, increased height (greater than the median value) was significantly associated with all-cause death and the composite aortic event when adjusted by age and sex (hazard ratio [HR]=2.22, 95%confidence interval [CI] 1.15-4.83, P=0.021, and HR=4.53, 95%CI 1.26-16.35, P=0.021, respectively). Patients with coexisting true aortic aneurysms also had a higher risk than those without (composite aortic events, HR=3.63, 95%CI 1.41-9.35, P=0.008). CONCLUSION: More strict management in the chronic phase is needed in taller patients as well as patients with coexisting true aortic aneurysms. This common physical predisposing feature may also assist in making the decision for earlier surgical intervention to the affected aorta.

[Combined pulmonary resection and cardiac operation; report of a case].

A 59-year-old woman was admitted because of an abnormal shadow on the chest X-ray film. Transbronchial lung biopsy revealed adenocarcinoma of the right lung, and chest computed tomography showed left atrial tumor. First, we performed a resection of left atrial tumor (myxoma) under cardiopulmonary bypass (CPB), followed by a right upper lobectomy with lymph node dissection. The postoperative course was uneventful, and she was discharged on the 14th postoperative day. It is safe and efficient that pulmonary resection and cardiac operation under CPB are surgically treated in a one-stage operation.

Three-dimensional optical coherence tomography of proliferative diabetic retinopathy.

Fourier-domain optical coherence tomography (OCT) was used to image the three-dimensional (3D) structures of the proliferative membrane in proliferative diabetic retinopathy. The case of a 51-year-old man with retinal detachment of the macula in his left eye is reported. The proliferative membrane covered the entire macular area. In the OCT image, the 3D structure of the proliferative membrane could be clearly visualised. The OCT image showed the presence of multiple adhesions between the retina and the proliferative membrane and separation of the proliferative membrane. The patient underwent three-port vitrectomy, and the extent and locations of the adhesions corresponded well with the findings during vitrectomy. Three-dimensional OCT is an effective tool for understanding the 3D structure of the proliferative membrane in diabetic retinopathy and is useful for training and planning of the surgical procedures in vitrectomy. To view the full report and accompanying video please go to: http://bjo.bmj.com/cgi/content/full/92/5/713/DC1. All videos from the BJO video report collection are available from: http://bjo.bmj.com/video/collection.dtl.

FTY720 suppresses CD4+CD44highCD62L- effector memory T cell-mediated colitis.

FTY720, a sphingosine-derived immunomodulator, causes immunosuppression via enhancement of lymphocyte sequestration into secondary lymphoid organs, thereby preventing their antigen-activated T cell egress to sites of inflammation. FTY720 is highly effective in inhibiting autoimmunity in various animal models. However, there is little known about how FTY720 controls the migration property of memory T cells. Here, we demonstrated that FTY720 prevents the development of colitis induced by the adoptive transfer of lamina propria (LP) colitogenic effector memory CD4+ T cells (TEM cells; CD45RB(low)CD44(high)CD62L-) into severe combined immunodeficiency (SCID) mice and suppresses interferon-gamma, interleukin-2, and tumor necrosis factor-alpha production by LP CD4+ T cells. The numbers of spleen, peripheral blood, mesenteric lymph node, and LP CD4+ T cells in FTY720-treated mice were significantly reduced compared with those in control mice. Notably, LP CD4+ TEM cells as well as splenic CD4+CD45RBhigh T cells expressed several spingosine-1-phosphate receptors that are targets for FTY720. Furthermore, FTY720 also prevented the development of colitis induced by the adoptive transfer of splenic CD4+CD45RBhigh T cells into SCID mice. Collectively, the present data indicate that FTY720 treatment may offer the potential not only to prevent the onset of disease but also to treat memory T cell-mediated autoimmune diseases including inflammatory bowel diseases.

Naturally arising CD4+CD25+ regulatory T cells suppress the expansion of colitogenic CD4+CD44highCD62L- effector memory T cells.

Naturally arising CD4+CD25+ regulatory T (T(R)) cells have been shown to prevent and cure murine T cell-mediated colitis. However, their exact mechanism of controlling colitogenic memory CD4+ T cells in in vivo systems excluding the initial process of naive T cell activation and differentiation has not been examined to date. Using the colitogenic effector memory (T(EM)) CD4+ cell-mediated colitis model induced by adoptive transfer of colitogenic CD4+CD44(high)CD62L(-) lamina propria (LP) T cells obtained from colitic CD4+CD45RB(high) T cell-transferred mice, we have shown in the present study that CD4+CD25+ T(R) cells are able not only to suppress the development of colitis, Th1 cytokine production, and the expansion of colitogenic LP CD4+ T(EM) cells but also to expand these cells by themselves extensively in vivo. An in vitro coculture assay revealed that CD4+CD25+ T(R) cells proliferated in the presence of IL-2-producing colitogenic LP CD4+ T(EM) cells at the early time point (48 h after culture), followed by the acquisition of suppressive activity at the late time point (96 h after culture). Collectively, these data suggest the distinct timing of the IL-2-dependent expansion of CD4+CD25+ T(R) cells and the their suppressive activity on colitogenic LP CD4+ T(EM) cells.

[Long survival with chronic ventricular fibrillation under support of uni-left-ventricular assist system].

Few minutes of suspended malignant ventricular arrhythmia may be permitted for the patient with left ventricular assist system (LVAS). However, longer and continuous ventricular arrhythmia, especially ventricular fibrillation (Vf), may induce the low output of LVAS, which leads circulatory collapse immediately. Our presenting case is a female dilated cardiomyopathy patient who has been supported with LVAS. Four months after the LVAS installation, her electrocardiogram has changed to Vf without any symptoms. Her ventricular function has never recovered, even ventricular tachycardia. She has been a candidate of heart transplantation for more than 19 months with this rare hemodynamic condition (LVAS+Vf), like the Fontan circulation. Her performance status is limited due to deceasing of the LVAS flow, which caused by the change of her position: 2.5-2.9 l/min (lie down) to 2.0 l/min (rise). Her peak VO2/W is 6.9 ml/min/kg measured by the cardio-pulmonary exercise test. However, she has developed her general status by doing rehabilitation program and is able to walk for more than 100-150 meters.

Treatment with buserelin, an agonist of gonadotropin-releasing hormone, suppresses ovarian hyperstimulation syndrome induced in rabbits.

Human menopausal gonadotropin (hMG, 75 IU/body/day) and a gonadotropin-releasing hormone (GnRH) agonist buserelin (1, 10, 100 microg/kg/day) were simultaneously administered to female rabbits by the subcutaneous route for 7 days, and the effects on organ weights, plasma hormones and weight of ascitic fluid were examined. Treatment with hMG increased the ovarian weight, plasma estradiol and weight of ascites, thus indicating that ovarian hyperstimulation syndrome had been induced. Simultaneous treatment with buserelin decreased the changes induced by hMG. GnRH agonists can thus be surmised to reduce the severity of ovarian hyperstimulation syndrome in the rabbit. However, caution is needed when extrapolating the results of this rabbit model to humans.

Human intestinal epithelial cell-derived interleukin (IL)-18, along with IL-2, IL-7 and IL-15, is a potent synergistic factor for the proliferation of intraepithelial lymphocytes.

Intestinal epithelial cell (IEC)-derived cytokines, such as stem cell factor (SCF), interleukin (IL)-7 and IL-15 are known to be required for the development of intestinal intraepithelial lymphocytes (IELs). A newly described cytokine, IL-18, has also been shown to be produced by intestinal epithelial cells. To demonstrate the functional effects of IL-18 on human IELs, we assessed IL-18/IL-18 receptor expression in IEC/IEL and proliferation following stimulation of intestinal IELs by IL-18. IL-18 transcripts were detected both in freshly isolated human colonic epithelial cells and in various colonic epithelial cell lines. IL-18 protein was also detected by ELISA and flow cytometric analysis using antihuman IL-18-specific monoclonal antibody (MoAb). Furthermore, IELs constitutively expressed the IL-18 receptor in addition to the IL-2 and IL-7 receptors. More importantly, IL-18 augmented significant proliferative responses of IEL in combination with IL-2, IL-7 and IL-15 both in the presence and in absence of anti-CD3 MoAb. These results suggest that IL-18 might play a crucial role in the proliferation and maintenance of intestinal IELs.

Normal development of the gut-associated lymphoid tissue except Peyer's patch in MyD88-deficient mice.

MyD88 is a key adaptor molecule for signalling via Toll-like receptors (TLRs) and the response to gut commensal microbes. To investigate the role of TLRs/MyD88 pathway in the development of the gut-associated lymphoid tissue (GALT), we examined the development of Peyer's patches (PPs) and cryptopatch (CP), and also one of effector compartment, intraepithelial lymphocyte (IEL) in MyD88-/-, TLR2-/- and TLR4-/- mice. In MyD88-/- mice, the organogenesis of PPs was not disturbed. However, PPs in 2-week-old MyD88-/- mice were significantly smaller than those in MyD88+/- mice. Also, in 2-week-old TLR4-/-, but not TLR2-/- mice, PPs did not develop rapidly. The development of PPs in MyD88-/- and TLR4-/- mice was completely recovered in 10 weeks. PP cells from MyD88-/- mice showed significant decrease in proliferation when stimulated with lipopolysaccharide. The development of CP and IEL was also normal in 10-week-old MyD88-/- mice. These results suggest that the TLRs/MyD88 pathway might be involved in the development of PPs only at early postnatal stage, and TLRs/MyD88-independent signalling is critically involved in the development of GALT in adult mice.

The role of cryptopatch-derived intraepithelial lymphocytes in the development of chronic ileocecitis.

Lympho-haemopoietic progenitors residing in murine gut cryptopatches (CPs) have been shown to generate intestinal extrathymic intraepithelial lymphocytes (IELs). However, the role of CPs in the development of intestinal inflammation remains unclear. To investigate the role of CPs in the development of intestinal inflammation, we examined SAMP1/Yit mice, which spontaneously develop a chronic intestinal inflammation localized to the terminal ileum and cecum. Here, we showed the sharp correlation between the disease onset and the decreased number of CPs, resulting in decreased number of both thymus-independent IELs including T-cell receptor gammadelta+ (TCRgammadelta+) and CD8alphaalpha+TCRalphabeta+ cells but not thymus-dependent CD8alphabeta+TCRalphabeta+ and CD4+TCRalphabeta+ cells in SAMP1/Yit mice. These data provide the first suggestion that thymus-independent IELs derived from CP might play protective role against the onset and the development of intestinal inflammation.

Spectral interferometric optical coherence tomography with nonlinear beta-barium borate time gating.

A high-speed, all optical coherence tomography system was designed and constructed. This tomography system employs spectral interferometry and optical Fourier transformation to reduce the number of mechanical scanning dimensions required for multidimensional profilometry. The system also employs a time gate comprising a beta -barium borate crystal driven by a femtosecond laser pulse to improve measurement time. This system has 43-mum depth resolution and 150-fs temporal resolution and is capable of taking 1000 cross-sectional image frames per second.

Birefringence imaging of human skin by polarization-sensitive spectral interferometric optical coherence tomography.

We have developed a spectral interferometric optical coherence tomography (OCT) system with polarization sensitivity that is able to measure a two-dimensional tomographic image by means of one-dimensional mechanical scanning. Our system, which has an axial resolution of 32 mum , calculates the distribution of each element of the Müller matrix of a measured object from 16 OCT images. The OCT system successfully reveals the birefringent nature of human skin tissue.

Dilation and reduced distensibility of carotid artery in patients with abdominal aortic aneurysms.

BACKGROUND: Although patients with abdominal aortic aneurysms (AAA) frequently have coexisting systemic atherosclerosis, the dilatative manifestation of AAA is the opposite of the occlusion characteristic of atherosclerotic disease. It has been suggested that this dilatative disease is caused by an alteration in connective tissue metabolism in systemic arterial wall. Such a condition might alter systemic arterial diameter and wall behavior. We investigated arterial characteristics in AAA patients, including morphologic changes and wall mechanics in the carotid artery. METHODS AND RESULTS: Atherosclerotic intimal changes such as intima-media thickness (IMT), plaque formation, diameter, and wall elasticity of the carotid artery were determined ultrasonographically in patients with AAA (n = 102) and compared with age-matched patients with the atherosclerotic diseases arteriosclerosis obliterans (ASO, n = 115) and coronary artery disease (CAD, n = 123) and with age-matched healthy control patients (CTL, n = 45). Intimal disease in AAA was significantly milder than in ASO, at the same level as CAD, and more severe than in CTL. Although end-diastolic luminal diameters (mm) in AAA (7.05 +/- 1.08), ASO (6.74 +/- 0.18), and CAD (6.66 +/- 0.83) were significantly higher than in CTL (5.97 +/- 0.93), they were also excessively increased compared with the equivalent diameters seen in ASO (P <.01) and CAD (P <.01). Luminal distensibility (x 10(-6) cm(2). dyne(-1)) in AAA (0.83 +/- 0.48) was excessively decreased compared not only with CTL (1.70 +/- 1.11, P <.01) but also with ASO (1.12 +/- 0.47, P <.01) and CAD (1.18 +/- 0.59, P <. 01). These relations remained true when adjusted for blood pressure and luminal diameter. Intra-AAA group analysis showed that distensibility in ruptured cases (n = 14) was significantly lower than in nonruptured cases (n = 88) (0.58 +/- 0.24 vs 0.88 +/- 0.50, P <.05). CONCLUSIONS: Excessive arterial dilation and reduced distensibility without severe intimal disease were found in the carotid arteries of patients with AAA. This suggests that these patients may be subject to systemic arterial alterations, including structural and functional abnormalities.