Maintenance and characterization of an Epstein Barr virus-infected CD56-negative T cell lymphoma.

T cell lymphoma carrying Epstein Barr virus (EBV(+) TL) is very rare among Western countries while it is much more common among Japanese. Here we report an EBV(+) TL which has been maintained for years by the use of mice with severe combined immune deficiency (SCID) mice. Lymphoma was obtained from a 55-year-old male suffering from oculomotor nerve palsy and lymphadenopathy. A small piece of biopsied tumor was transplanted into SCID mice and the lymphoma has been maintained for over 3 years with passages every 2 - 3 weeks. The maintained lymphoma, termed as TMS24, and the original lymphoma cells showed identical phenotype and genotype, including diffuse medium-sized cell morphology lacking granules, suppressor / cytotoxic immunophenotype and identical T cell receptor beta-chain gene rearrangement mode. Further, both were shown to carry an identical EBV clone in terms of the number of terminal repeats and the latency II-type restricted gene expression profile. Cytogenetically, TMS24 retained two characteristic chromosomal translocations of t(1;18)(q32;q21) and t(6;12)(p21;q24). Since only one cell line with such characters has been reported previously, TMS24 should be useful for detailed analysis of EBV(+) TL.     

TP53 variants in p53 signatures and the clonality of STICs in RRSO samples

ObjectivePrecursor lesions may be identified in fallopian tube tissue after risk-reducing salpingo-oophorectomy (RRSO) in patients with pathogenic variants of BRCA1/2. Serous tubal intraepithelial carcinoma (STIC) is considered a precursor of high-grade serous carcinoma, whereas the significance of the p53 signature remains unclear. In this study, we investigated the relationship between the p53 signature and the risk of ovarian cancer.MethodsWe analyzed the clinicopathological findings and conducted DNA sequencing for TP53 variants of p53 signatures and STIC lesions isolated using laser capture microdissection in 13 patients with pathogenic variants of BRCA1/2 who underwent RRSO and 17 control patients with the benign gynecologic disease.Results TP53 pathogenic variants were detected significantly higher in RRSO group than control (p<0.001). No difference in the frequency of p53 signatures were observed between groups (53.8% vs 29.4%; p=0.17). TP53 sequencing and next-generation sequencing analysis in a patient with STIC and occult cancer revealed 2 TP53 mutations causing different p53 staining for STICs and another TP53 mutation shared between STIC and occult cancer.ConclusionThe sequence analysis for TP53 revealed 2 types of p53 signatures, one with a risk of progression to STIC and ovarian cancer with pathological variants in TP53 and the other with a low risk of progression without pathological variants in TP53 as seen in control.     

Correlation between a Bedridden Status and the Long-term Outcome in Hemodialysis Patients after Intracerebral Hemorrhaging

Objective The quality of life and activities of daily living (ADL) are generally poor among dialysis patients after intracerebral hemorrhaging, and their precise clinical course remains unclear. In addition, the association between the severity of cerebral hemorrhaging and the long-term prognosis in these patients has not been fully elucidated. This study aimed to evaluate the subsequent prognosis of hemodialysis patients who survived the acute phase of intracerebral hemorrhaging. Methods We included hemodialysis patients who were admitted to Nagasaki University Hospital between 2007 and 2015 for intracerebral hemorrhaging treatment. After excluding cases of in-hospital death, survivors were classified using the 5-point modified Rankin Scale (mRS), which specifically measures the ADL in patients with cerebrovascular diseases. The patients were followed up at the medical facilities to which they were transferred in the same medical zone until 2017. Results Out of 91 patients with cerebral hemorrhaging (65±11 years old, 66% men, hemodialysis duration 108±91 months), 62 survived until discharge. Twenty-one patients died during observation, largely due to infectious diseases, such as sepsis and pneumonia (n=16, 76%). Compared to patients with mRS 0-4 (n=31), those with mRS 5 (n=31) showed a significantly poorer prognosis. The hazard ratio adjusted for age and antiplatelets was 13.7 (95% confidence interval: 3.88-63.7, p<0.001). Conclusion Hemodialysis patients with intracerebral hemorrhaging who were bedridden showed poor outcomes. The major causes of death were infections. Therefore, these patients should be carefully monitored for infections in order to improve their prognosis.     

Evaluation of beam hardening and photon scatter by brass compensator for IMRT

When a brass compensator is set in a treatment beam, beam hardening may take place. This variation of the energy spectrum may affect the accuracy of dose calculation by a treatment planning system and the results of dose measurement of brass compensator intensity modulated radiation therapy (IMRT). In addition, when X-rays pass the compensator, scattered photons are generated within the compensator. Scattered photons may affect the monitor unit (MU) calculation. In this study, to evaluate the variation of dose distribution by the compensator, dose distribution was measured and energy spectrum was simulated using the Monte Carlo method. To investigate the influence of beam hardening for dose measurement using an ionization chamber, the beam quality correction factor was determined. Moreover, to clarify the effect of scattered photons generated within the compensator for the MU calculation, the head scatter factor was measured and energy spectrum analyses were performed. As a result, when X-rays passed the brass compensator, beam hardening occurred and dose distribution was varied. The variation of dose distribution and energy spectrum was larger with decreasing field size. This means that energy spectrum should be reproduced correctly to obtain high accuracy of dose calculation for the compensator IMRT. On the other hand, the influence of beam hardening on k_Q was insignificant. Furthermore, scattered photons were generated within the compensator, and scattered photons affect the head scatter factor. These results show that scattered photons must be taken into account for MU calculation for brass compensator IMRT.     

Evaluation of olfactory dysfunction to estimate the presence of eosinophilic chronic rhinosinusitis in patients with asthma

BackgroundEosinophilic chronic rhinosinusitis (ECRS) is often complicated by asthma and can be difficult to diagnose. This study aimed to clarify the usefulness of the self-administered odor questionnaire (SAOQ) and visual analog scale (VAS) to identify olfactory disorders in patients with asthma.MethodsThis retrospective study was conducted on patients with asthma who were referred to the Otolaryngology clinic between May and September 2018. The treatment step of asthma, asthma control test (ACT), pulmonary function test, peripheral blood eosinophils, and fractional exhaled nitric oxide (FeNO) were analyzed. ECRS was diagnosed based on the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis Study score. Olfactory dysfunction was evaluated using the SAOQ and VAS for olfactory disorders.ResultsThe study included 56 patients (18 males and 38 females), who were divided into two groups; those with ECRS (n = 18) and those without ECRS (n = 38). Age, sex, treatment step, ACT score, and pulmonary function were not significantly different between the groups. The ECRS group had a significantly higher FeNO value (89.1 ppb vs. 39.1 ppb) and a significantly lower SAOQ score (40.1% vs. 96.1%). The area under the receiver operating characteristic curve for the efficacy of ECRS diagnosis was 0.88, 0.889, 0.799, and 0.757 for SAOQ, VAS, blood eosinophil count, and FeNO, respectively.ConclusionThe SAOQ and VAS scores were useful tools that presented similar results to the blood eosinophil count and FeNO, and may help to improve the diagnosis of ECRS in patients with asthma.     

Identification of the optimal structure required for a Shiga toxin neutralizer with oriented carbohydrates to function in the circulation

Shiga toxin (Stx) is a major virulence factor of Stx-producing Escherichia coli. Recently, we developed a therapeutic Stx neutralizer with 6 trisaccharides of globotriaosyl ceramide, a receptor for Stx, in its dendrimer structure (referred to as "SUPER TWIG [1]6") to function in the circulation. Here, we determined the optimal structure of SUPER TWIG for it to function in the circulation and identified a SUPER TWIG with 18 trisaccharides, SUPER TWIG (2)18, as another potent Stx neutralizer. SUPER TWIGs (1)6 and (2)18 shared a structural similarity, a dumbbell shape in which 2 clusters of trisaccharides were connected via a linkage with a hydrophobic chain. The dumbbell shape was found to be required for formation of a complex with Stx that enables efficient uptake and degradation of Stx by macrophages and, consequently, for potent Stx-neutralizing activity in the circulation. We also determined the binding site of the SUPER TWIGs on Stx.     

A case of factor X (FX) deficiency due to novel mutation V196M,FX Hofu

The patient, a 20-year-old male, was found to have a slightly prolonged prothrombin time (PT). No episodes of bleeding were noted. The measurement of coagulation factors revealed that the level of factor X (FX) activity was solely deficient, 51% (normal range: 70–130% ), and that of FX antigen was 100%. Analysis of the entire FX gene revealed the novel missense mutation of GTG to ATG, resulting in the substitution of the 196th amino acid valine → methionine. The mother and younger brother had a normal PT time and expressed no episode of bleeding. The mother exhibited a normal level of FX activity and antigen; however the younger brother showed a slight decrease in both the parameters. This mutation was not observed in the mother and younger brother. Polymorphism is not observed at this point in healthy persons. The present novel FX mutation was named FX Hofu.     

Transmission of Helicobacter pylori from Challenged to Nonchallenged Nude Mice Kept in a Single Cage

To determine the transmission route of Helicobacter pylori, one nude mouse was challenged by H. pylori, and then raised with nonchallenged nude mice in a single cage in a sterilized environment with and without exposure to their feces. After coraising for two and four weeks, all mice were killed to determine H. pylori in the stomach, saliva, and feces and to assess gastritis grade. Natural transmission of H. pylori occurred in 50% (2/4) and 70% (7/10) of mice after two weeks and four weeks of coraising when they were exposed to their feces. H. pylori was detected not only in the stomach but also in saliva and feces by PCR of all challenged and transmitted mice. However, no transmission occurred in mice not exposed to feces of a challenged mouse, while sharing food and water in a single cage. These findings suggest that the fecal–oral transmission route is important, at least in the animal model. Serum levels of anti-H. pylori urease IgG of the H. pylori-transmitted mice increased after coraising, and gastritis was observed in the stomach of both challenged and transmitted mice. We conclude that H. pylori bacteria are transmitted through the fecal–oral route from challenged to nonchallenged nude mice, resulting in gastritis.