Two Cases of Cerebral Involvement in Malignant Lymphoma (CD20+) That Responded to Combination Therapy with Rituximab and Cladribine

Cerebral involvement frequently occurs in association with progression or relapse of malignant lymphoma. Chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisolone, the standard chemotherapy for malignant lymphoma, is an ineffective treatment for cerebral involvement because these drugs cannot cross the blood-brain barrier. Therefore, various alternative strategies have been attempted. Although high-dose methotrexate combined with whole-brain radiotherapy is widely used to treat primary central nervous system lymphoma, there is no standard therapy to treat cerebral involvement in malignant lymphoma. Furthermore, high-dose methotrexate in combination with whole-brain radiotherapy is not always effective, and high rates of neurotoxicity are often observed, particularly in the elderly. To expand the therapeutic options for central nervous system involvement in recent years, systemic chemotherapies, including rituximab, high-dose methotrexate, and other agents that act during the S, G2, and M phases of the cell cycle, have been attempted. In our hospital, cladribine, a purine analogue with a cytocidal effect on resting malignant cells (G0/G1 phase of the cell cycle), has been used in combination with rituximab, which exhibits antitumor effects on nodal and extranodal lesions of relapsed and/or refractory B cell lymphomas, particularly cerebral lesions. Here, we report 2 representative cases of patients who were treated with cladribine plus rituximab and survived for 30 months (died of sepsis) and 52 months (still alive), respectively. The outcomes of these cases suggest that cladribine plus rituximab combination therapy with whole-brain radiotherapy may be very useful as salvage therapy for secondary central nervous system lymphoma and as initial therapy for primary central nervous system lymphoma

Observation of finite excess noise in the voltage-biased quantum Hall regime as a precursor for breakdown

We performed noise measurements in a two-dimensional electron gas to investigate the nonequilibrium quantum Hall effect (QHE) state. While excess noise is perfectly suppressed around the zero-biased QHE state reflecting the dissipationless electron transport of the QHE state, considerable finite excess noise is observed in the breakdown regime of the QHE. The noise temperature deduced from the excess noise is found to be of the same order as the energy gap between the highest occupied Landau level and the lowest empty one. Moreover, unexpected finite excess noise is observed at a finite source-drain bias voltagesmaller than the onset voltage of the QHE breakdown, which indicates finite dissipation in the QHE state and may be related to the prebreakdown of the QHE.Comment: 8 pages, 8 figure

COVID-19 mRNA Vaccine–Associated Uveitis Leading to Diagnosis of Sarcoidosis: Case Report and Review of Literature

A 34-year-old Japanese person with male gender identity who had been taking intramuscular injection of methyltestosterone depot for 11 years after bilateral mastectomy noticed blurred vision 5 days after the second vaccination for COVID-19 (Tozinameran; Pfizer-BioNTech) in the interval of 3 weeks following the first vaccination. The patient was diagnosed as granulomatous iritis with mutton-fat keratic precipitates and small iris nodules at the pupillary margin in the right eye and began to have 0.1% betamethasone eye drops with good response. The patient, however, continued to have fever and malaise and showed a high level of serum soluble interleukin-2 receptor (sIL-2R) even 4 weeks after the second vaccination. Computed tomographic scan disclosed mediastinal and bilateral hilar small lymphadenopathy together with limited granular lesion in the right lung. Gallium-67 scintigraphy demonstrated high uptake not only in mediastinal and hilar lymph nodes but also in bilateral parotid glands. Right parotid gland biopsy revealed noncaseating granulomas and proved pathological diagnosis of sarcoidosis. The systemic symptoms were relieved by oral prednisolone 20 mg daily. Even though the causal relationship remains undetermined, this case is unique at the point that vaccine-associated uveitis led to the detection of pulmonary lesions and lymphadenopathy, resulting in clinical and pathological diagnosis of sarcoidosis. In literature review, 3 patients showed sarcoidosis-like diseases after COVID-19 vaccination: 2 patients were diagnosed clinically as Lofgren syndrome with acute onset of erythema nodosum and ankle swelling, with or without mediastinal and hilar lymphadenopathy, whereas 1 patient with mediastinal lymphadenopathy but no uveitis was diagnosed pathologically by biopsy as sarcoidosis. </jats:p

Experimental Verification of a One-Dimensional Diffraction-Limit Coronagraph

We performed an experimental verification of a coronagraph. As a result, we confirmed that, at the focal region where the planetary point spread function exists, the coronagraph system mitigates the raw contrast of a star-planet system by at least $1\times10^{-5}$ even for the 1-$\lambda/D$ star-planet separation. In addition, the verified coronagraph keeps the shapes of the off-axis point spread functions when the setup has the source angular separation of 1$\lambda/D$. The low-order wavefront error and the non-zero extinction ratio of the linear polarizer may affect the currently confirmed contrast. The sharpness of the off-axis point spread function generated by the sub-$\lambda/D$ separated sources is promising for the fiber-based observation of exoplanets. The coupling efficiency with a single mode fiber exceeds 50% when the angular separation is greater than 3--4$\times 10^{-1}\lambda/D$. For sub-$\lambda/D$ separated sources, the peak positions (obtained with Gaussian fitting) of the output point spread functions are different from the angular positions of sources; the peak position moved from about $0.8\lambda/D$ to $1.0\lambda/D$ as the angular separation of the light source varies from $0.1\lambda/D$ to $1.0\lambda/D$. The off-axis throughput including the fiber-coupling efficiency (with respect to no focal plane mask) is about 40% for 1-$\lambda/D$ separated sources and 10% for 0.5-$\lambda/D$ separated ones (excluding the factor of the ratio of pupil aperture width and Lyot stop width), where we assumed a linear-polarized-light injection. In addition, because this coronagraph can remove point sources on a line in the sky, it has another promising application for high-contrast imaging of exoplanets in binary systems.Comment: 18 pages, 10 figures, accepted for the Publications of the Astronomical Society of the Pacifi

A Review of Oxidative Stress and Urinary Dysfunction Caused by Bladder Outlet Obstruction and Treatments Using Antioxidants

Urinary dysfunction is a common pathological condition that can significantly decrease the quality of life.Bladder outlet obstruction (BOO) is a major cause of urinary dysfunction, and various lower urinary tract diseases including benign prostatic hyperplasia and urethral stricture disease cause BOO. According to the results of a variety of animal experiments on partial BOO (PBOO), there is a general agreement that ischemic conditions and repeated ischemia/reperfusion of the bladder are closely associated with BOO-induced bladder damage, and that increased oxidative stress by ischemia/reperfusion plays a crucial role in the pathological mechanisms underlying urinary dysfunction. Changes in biomarkers of oxidative stress in PBOO animal models support this association between oxidative stress and urinary dysfunction. Oxidative stress is defined as an imbalance between the production of pro-oxidants, such as free radicals and reactive species, and their elimination through protective mechanisms of antioxidants. Therefore, organizing the knowledge on the state of oxidative stress, changes in biomarkers, and biological roles of antioxidants in systemic and bladder tissues is essential to understand the detailed pathological characteristics of the urinary dysfunction caused by PBOO. Furthermore, information on drugs and supplements that have antioxidant effects is important for defining treatment strategies for urinary dysfunction with PBOO. In this review, we paid special attention to the following three issues; (1) changes in oxidative stress, including its biomarkers, (2) antioxidant status, and (3) previous reports on treatment strategies involving agents with antioxidative activity for urinary dysfunction caused by BOO. In particular, we provide systematic information on the detailed mechanisms underlying the antioxidative effects of agents used to treat PBOO. In addition, we show present research issues and research limitations, as well as suggest possible future antioxidant treatment strategies for patients with PBOO

High expression of Twist is associated with tumor aggressiveness and poor prognosis in patients with renal cell carcinoma

Aims: Twist has been reported to play crucial roles for malignant aggressiveness; however, detailed pathological significance of Twist in renal cell carcinoma (RCC) is not fully understood. The present study was to clarify clinical significance and molecular functions of Twist in patients with RCC. Methods: Twist expression was examined by immunohistochemical techniques in 156 formalin-fixed specimens. Cell proliferation, angiogenesis, and apoptosis were measured as the percentage of Ki-67-positive cells (proliferation index, PI), CD31-stained vessels (microvessel density, MVD), and TUNEL-positive cells (apoptotic index, AI). In addition, semi-quantification of matrix metalloproteinase (MMP)-2 was performed. Macrophages were identified with anti-CD68 antibody, and the tumor associated macrophage (TAM) density was calculated as CD68-positive cells per high-power field. Results: Twist expression was positively associated with grade, pT stage, and metastasis (p<0.001). We also noticed that its expression was considerably higher in cancer cells of sarcomatoid RCC and in those at the edge of the tumors. Twist expression was positively correlated with PI, MVD, MMP2 expression, and TAM density (P<0.001), but not with AI, and MMP-2 expression and TAM density were independently correlate by multi-variate analyses. Kaplan-Meir survival curves showed high Twist expression was a worse predictor for cause-specific survival (P<0.001). Conclusions: Twist plays important roles in tumor growth, progression, and survival in patients with RCC patients. Such pathological mechanisms are significantly associated with increased cancer cell proliferation, angiogenesis, MMP2 expression, and macrophage recruitment. These findings are important information for discussion of treatment and observation strategies in these patients