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Background: We studied the clinicopathological characteristics and prognoses of localized stage thyroid diffuse large B-cell lymphoma (DLBCL). Patients and methods: This study included 32 patients with stage I/IIE thyroid DLBCL. Their median age was 66 years, the male/female ratio was 10/22. Results: As to the cellular immunophenotype, CD20 was positive in 31/32, CD5 in 0/32, CD10 in 4/32, CD23 in 1/32, BCL2 in 14/30, and BCL6 in 24/32. Twelve cases showed abnormal karyotypes: two cases with t(8;14)(q24;q32), four cases with 3q27, two cases with 17p11, and four cases with other abnormal karyotypes. As for treatment, eight cases were treated with chemotherapy alone and 24 cases were treated with chemotherapy followed by radiotherapy. Complete response was achieved in 94%. The 5-year progression-free survival was 84% and the 5-year overall survival was 90% with a median follow-up period of 62 months. The germinal center B-cell (GCB) type had a significantly better prognosis than the non-GCB type. Conclusion: Localized stage thyroid DLBCL is a disease with a relatively good prognosis. It is, however, a heterogeneous disease with regard to histological type and pathological state. Localized stage thyroid DLBCL has a good prognosis and it is that there are more GCB-type DLBCL lymphomas. [ABSTRACT FROM AUTHOR]

Bioluminescence is a widespread phenomenon that has evolved multiple times across the tree of life, converging among diverse fauna and habitat types. The ubiquity of bioluminescence, particularly in marine environments where it is commonly used for communication and defense, highlights the adaptive value of this trait, though the evolutionary origins and timing of emergence remain elusive for a majority of luminous organisms. Anthozoan cnidarians are a diverse group of animals with numerous bioluminescent species found throughout the world's oceans, from shallow waters to the light-limited deep sea where bioluminescence is particularly prominent. This study documents the presence of bioluminescent Anthozoa across depth and explores the diversity and evolutionary origins of bioluminescence among Octocorallia-a major anthozoan group of marine luminous organisms. Using a phylogenomic approach and ancestral state reconstruction, we provide evidence for a single origin of bioluminescence in Octocorallia and infer the age of occurrence to around the Cambrian era, approximately 540 Ma-setting a new record for the earliest timing of emergence of bioluminescence in the marine environment. Our results further suggest this trait was largely maintained in descendants of a deep-water ancestor and bioluminescent capabilities may have facilitated anthozoan diversification in the deep sea.

Objectives: To evaluate caregivers' fear of post-fracture patients falling, we previously developed the Caregivers' Fear of Falling Index (CFFI). In this study, we investigated the relationship between patient performance in activities of daily living (ADLs) and CFFI., Methods: We surveyed 55 patients receiving home-visit rehabilitation after fall-related fracture and their primary caregivers. Participants (patient and caregiver pair) were divided into two groups based on patient performance in basic ADLs (BADLs) and instrumental ADLs (IADLs). ROC analysis was conducted to assess the usefulness of CFFI and Falls Efficacy Scale-International (FES-I) in determining declines in performance in BADLs and IADLs. Multivariate logistic regression analysis was performed to examine the association between CFFI and declining performance in BADLs and IADLs., Results: ROC analysis showed that CFFI exhibited a higher accuracy than FES-I (AUC: 0.73 in BADLs, 0.77 in IADLs) as an indicator of reduced ADL performance. Multivariate logistic analysis adjusted for age, sex, and physical function showed that CFFI was associated with a decline in patients' performance in IADLs (odds ratio, 0.92; 95% confidence interval, 0.85-0.99)., Conclusions: Caregivers' fear of post-fracture patients falling was associated with a decline in patients' performance in IADLs. These findings may serve as a guide for supporting caregivers of post-fracture patients., Competing Interests: CONFLICTS OF INTEREST: The authors declare no conflict of interest., (2023 The Japanese Association of Rehabilitation Medicine.)

Lobella sauteri was redescribed based on the lectotype and specimens obtained from the type locality Bugenji, Yokohama, Kanagawa, as the true identity of the luminous Collembola, Lobella sp. Lobella sauteri has morphological traits characteristic of the genus currently called Telobella. As L. sauteri is the type species of Lobella, the genus Telobella was synonymised with Lobella according to the principle of priority, and the genus Lobella was redefined to include both the species previously assigned to Telobella and those previously assigned to Lobella. A new species Lobella monstrum sp. nov. was described and new combinations were proposed for certain species in Lobellini. Light-emitting capacity was confirmed in L. sauteri and newly reported in Lobella yambaru comb. nov. Vitronura giselae and Vitronura kunigamiensis.

Objective: To evaluate the reliability and validity of this new measure, called the caregivers' fear of falling index (CFFI)., Methods: The study surveyed home-based rehabilitation patients with fall-related fracture, and their primary caregivers. The characteristics of these patients were evaluated, and the caregivers were surveyed using the CFFI and Falls Efficacy Scale-International (FES-I). The reliability of the CFFI was assessed using item-total correlation, while the validity of the CFFI was evaluated through correlation coefficients calculated between the CFFI and the FES-I., Results: The participants were 51 patient-caregiver pairs. The internal consistency of the CFFI showed an alpha coefficient of 0.904. No items were excluded in the corrected item-total correlations. The CFFI showed a moderate correlation with FES-I (r=0.432, p=0.002)., Conclusion: This study found the CFFI to be a reliable and valid tool for measuring the primary caregivers' fear. The CFFI may be a useful tool for healthcare professionals to identify and supporting these primary caregivers.

Bioluminescence, a phenomenon observed widely in organisms ranging from bacteria to metazoans, has a significant impact on the behaviour and ecology of organisms. Among bioluminescent organisms, Polycirrus , which has unique emission wavelengths, has received attention, and advanced studies such as RNA-Seq have been conducted, but they are limited to a few cases. In addition, accurate species identification is difficult due to lack of taxonomic organization. In this study, we conducted comprehensive taxonomic survey of Japanese Polycirrus based on multiple specimens from different locations and described as three new species: Polycirrus onibi sp. nov., P . ikeguchii sp. nov. and P . aoandon sp. nov. The three species can be distinguished from the known species based on the following characters: (i) arrangement of mid-ventral groove, (ii) arrangement of notochaetigerous segments, (iii) type of neurochaetae uncini, and (iv) arrangement of nephridial papillae. By linking the bioluminescence phenomenon with taxonomic knowledge, we established a foundation for future bioluminescent research development. We also provide a brief phylogenetic tree based on cytochrome c oxidase subunit I (COI) sequences to discuss the evolution of bioluminescence and the direction of future research., Competing Interests: We declare we have no competing interests., (© 2023 The Authors.)

Cisplatin- and gemcitabine-based chemotherapeutics represent a mainstay of cancer therapy for most solid tumors; however, resistance limits their curative potential. Here, we identify RNA polymerase II-associated factor 1 (PAF1) as a common driver of cisplatin and gemcitabine resistance in human cancers (ovarian, lung, and pancreas). Mechanistically, cisplatin- and gemcitabine-resistant cells show enhanced DNA repair, which is inhibited by PAF1 silencing. We demonstrate an increased interaction of PAF1 with RAD52 in resistant cells. Targeting the PAF1 and RAD52 axis combined with cisplatin or gemcitabine strongly diminishes the survival potential of resistant cells. Overall, this study shows clinical evidence that the expression of PAF1 contributes to chemotherapy resistance and worse clinical outcome for lethal cancers., Competing Interests: Declaration of interests S.K.B. is one of the co-founders of Sanguine Diagnostics and Therapeutics, Inc. The other authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The lanternfish is a deep-sea fish with ventral-lateral and head photophores. It uses its ventral-lateral photophores to camouflage its ventral silhouette, a strategy called counterillumination. The bioluminescent reaction of lanternfish involves coelenterazine as a substrate luciferin but the enzyme catalyzing the bioluminescent reaction has not been identified. We report a candidate enzyme of luciferase from lanternfish Diaphus watasei. We purified the luciferase and performed SDS-PAGE analysis resulted in two bands corresponding to the activity, and following mass spectrometry analysis detected three 14-3-3 proteins of which functions is known to exhibit protein-protein interactions. The molecular weights and isoelectric points of the 14-3-3 proteins were almost consistent with the luciferase properties. The addition of two 14-3-3 binding compounds, R18 peptide and fusicoccin, resulted in the inhibition of the luciferase activity. However, the two 14-3-3 recombinant proteins showed very slight luminescence activity. These results suggested that the 14-3-3 proteins are candidate luciferases of D. watasei., (© 2022. The Author(s), under exclusive licence to European Photochemistry Association, European Society for Photobiology.)

This study aimed to identify evaluation items that can be used to create an index to evaluate caregivers' fear of care recipient falls. A three-round Delphi method was conducted with medical professionals engaged in discharge support for patients with fall-related fractures. In the first round, a working group brainstormed evaluation items. In the second and third rounds, opinions of medical professionals were quantified and evaluation items were refined. The Delphi method showed convergence of opinion with Kendall's W of 0.561 in the third round. Of the 109 evaluation items pooled in the first round, the consensus was reached on the importance of 19 items and one more item was additionally included. The 20 items may be useful for creating an index that sensitively measures caregivers' fear of care recipient falls., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Bioluminescence is a natural light emitting phenomenon that occurs due to a chemical reaction between luciferin and luciferase. It is primarily an innate and inherited trait in most terrestrial luminous organisms. However, most luminous organisms produce light in the ocean by acquiring luminous symbionts, luciferin (substrate), and/or luciferase (enzyme) through various transmission pathways. For instance, coelenterazine, a well-known luciferin, is obtained by cnidarians, crustaceans, and deep-sea fish through multi-level dietary linkages from coelenterazine producers such as ctenophores, decapods, and copepods. In contrast, some non-luminous Vibrio bacteria became bioluminescent by obtaining lux genes from luminous Vibrio species by horizontal gene transfer. Various examples detailed in this review show how non-luminescent organisms became luminescent by acquiring symbionts, dietary luciferins and luciferases, and genes. This review highlights three modes (symbiosis, ingestion, and horizontal gene transfer) that allow organisms lacking genes for autonomous bioluminescent systems to obtain the ability to produce light. In addition to bioluminescence, this manuscript discusses the acquisition of other traits such as pigments, fluorescence, toxins, and others, to infer the potential processes of acquisition., (© 2021. The Author(s), under exclusive licence to European Photochemistry Association, European Society for Photobiology.)

Synthetic lethality is a successful strategy employed to develop selective chemotherapeutics against cancer cells. Inactivation of RAD52 is synthetically lethal to homologous recombination (HR) deficient cancer cell lines. Replication protein A (RPA) recruits RAD52 to repair sites, and the formation of this protein-protein complex is critical for RAD52 activity. To discover small molecules that inhibit the RPA:RAD52 protein-protein interaction (PPI), we screened chemical libraries with our newly developed Fluorescence-based protein-protein Interaction Assay (FluorIA). Eleven compounds were identified, including FDA-approved drugs (quinacrine, mitoxantrone, and doxorubicin). The FluorIA was used to rank the compounds by their ability to inhibit the RPA:RAD52 PPI and showed mitoxantrone and doxorubicin to be the most effective. Initial studies using the three FDA-approved drugs showed selective killing of BRCA1-mutated breast cancer cells (HCC1937), BRCA2-mutated ovarian cancer cells (PE01), and BRCA1-mutated ovarian cancer cells (UWB1.289). It was noteworthy that selective killing was seen in cells known to be resistant to PARP inhibitors (HCC1937 and UWB1 SYr13). A cell-based double-strand break (DSB) repair assay indicated that mitoxantrone significantly suppressed RAD52-dependent single-strand annealing (SSA) and mitoxantrone treatment disrupted the RPA:RAD52 PPI in cells. Furthermore, mitoxantrone reduced radiation-induced foci-formation of RAD52 with no significant activity against RAD51 foci formation. The results indicate that the RPA:RAD52 PPI could be a therapeutic target for HR-deficient cancers. These data also suggest that RAD52 is one of the targets of mitoxantrone and related compounds., Competing Interests: The authors have declared that no competing interests exist.

Coelenterazine is a key substrate involved in marine bioluminescence which is used for light-production by at least nine phyla. Some luminous animals, such as the hydromedusa Aequorea , lack the ability to produce coelenterazine endogenously and instead depend on dietary sources. Little is known about the source organisms or the metabolic process of coelenterazine biosynthesis. Here, we present evidence that ctenophores are both producers and suppliers of coelenterazine in marine ecosystems. Using biochemical assays and mass spectrometry analyses, we detected coelenterazine from cultured ctenophores fed with a non-luminous coelenterazine-free diet. We propose that ctenophores are an emerging model organism to study coelenterazine biosynthesis and the origins of bioluminescence., Competing Interests: The authors declare no competing interests., (© 2020 The Authors.)

To determine the impact of peripheral blood (PB) Wilms' tumour 1 ( WT-1 ) mRNA levels in patients with primary myelodysplastic syndromes (MDS), we analysed the relationships between several clinical variables at the time of diagnosis and the haematological response of patients treated with azacytidine. We observed overall responses in 20 (63%) patients; there were no significant differences in clinical variables, including bone marrow blast counts, IPSS scores and IPSS-R risk scores, between responders and non-responders. The responders' PB WT-1 mRNA levels were significantly lower than those of non-responders ( P  = 0.03). PB WT-1 mRNA expression could be a marker for predicting the response to azacytidine in patients with de novo MDS., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Tomoya Maeda has received honoraria from Nippon Shinyaku and advisory boards for Janssen. Akira Matsuda has received honoraria from GlaxoSmithKline, Kyowa Kirin, Nippon Shinyaku, Celgene, Alexion, Sanofi, Beckman Coulter, Siemens Healthineers and Shire Japan. Maho Ishikawa has received honoraria from Bristol-Myers Squibb and Pfizer. Kunihiro Tsukasaki has a consultancy in Daiich-Sankyo, Ono Pharma, and HUYA, has received research funding from Bayer and Celgene, and honoraria from Chugai Pharma, Celgene, Mundy and Kyowa Kirin. Norio Asou has received scholarships from Chugai Pharma, Astellas, Sumitomo Dainippon and Eisai and research funding from Novartis and Otsuka Pharma, has consulted for SRL, Nippon Shinyaku, and Novartis and has received honoraria from Kyowa Kirin, Sumitomo Dainippon, Asahi Kasei and Fuji Pharma. Masami Bessho has received honoraria from Chugai Pharma and GlaxoSmithKline. These sponsors had no control over the interpretation, writing or publication of this study. The other authors have no declaration of conflicts of interest to declare in relation to this manuscript., (© 2020 The Author(s). Published by Elsevier Ltd.)

Through their diet, animals can obtain substances essential for imparting special characteristics, such as toxins in monarch butterflies and luminescent substances in jellyfishes. These substances are typically small molecules because they are less likely to be digested and may be hard for the consumer to biosynthesize. Here, we report that Parapriacanthus ransonneti , a bioluminescent fish, obtains not only its luciferin but also its luciferase enzyme from bioluminescent ostracod prey. The enzyme purified from the fish's light organs was identical to the luciferase of Cypridina noctiluca , a bioluminescent ostracod that they feed upon. Experiments where fish were fed with a related ostracod, Vargula hilgendorfii , demonstrated the specific uptake of the luciferase to the fish's light organs. This "kleptoprotein" system allows an organism to use novel functional proteins that are not encoded in its genome and provides an evolutionary alternative to DNA-based molecular evolution., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Background: It is important to assess the fracture risk associated with metastasis in the proximal femur. The study aimed to clarify the effect of tumor location on the risk of pathological fracture of the proximal femur and investigate the fracture risk not only in the stance-loading configuration (SC), but also in the fall-loading configuration (FC) using a computed tomography (CT)-based finite element (FE) method based on a simulated metastatic model., Methods: The axial CT scans of the proximal femora of non-osteoporotic healthy men (n = 4; age range, 42-48 years) and osteoporotic post-menopausal women (n = 4; age range, 69-78 years) were obtained with a calibration phantom, from which the three-dimensional FE models were constructed. A single 15-mm-diameter spherical void simulating a tumor was created at various locations from the neck to subtrochanteric level. Nonlinear FE analyses were performed., Results: The mean predicted fracture loads without spherical voids in the SC were 7700 N in men and 4370 N in women. With the void at the medial femoral neck and in the region anteromedial to lesser trochanter, the mean predicted fracture load significantly reduced to 51.3% and 59.4% in men and 34.1% and 64.5% in women, respectively. The mean predicted fracture loads without a spherical void in the FC were 2500 N in men and 1862 N in women. With the void at the medial and posterior femoral neck, the predicted fracture load was significantly reduced to 65.7% and 79.7% in men and 48.3% and 65.4% in women, respectively., Conclusions: These results showed that the risk of pathologic fracture was quite high in both the SC and FC when the lytic lesion existed along the principal compressive trabecular trajectory or posterior neck. Prophylactic intervention should be considered for metastases at these locations., (Copyright © 2019 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Thermophilic enzymes are generally more thermally stable but are less active at moderate temperatures than are their mesophilic counterparts. Thermophilic enzymes with improved low-temperature activity that retain their high stability would serve as useful tools for industrial processes especially when robust biocatalysts are required. Here we show an effective way to explore amino acid substitutions that enhance the low-temperature catalytic activity of a thermophilic enzyme, based on a pairwise sequence comparison of thermophilic/mesophilic enzymes. One or a combination of amino acid(s) in 3-isopropylmalate dehydrogenase from the extreme thermophile Thermus thermophilus was/were substituted by a residue(s) found in the Escherichia coli enzyme at the same position(s). The best mutant, which contained three amino acid substitutions, showed a 17-fold higher specific activity at 25 °C compared to the original wild-type enzyme while retaining high thermal stability. The kinetic and thermodynamic parameters of the mutant showed similar patterns along the reaction coordinate to those of the mesophilic enzyme. We also analyzed the residues at the substitution sites from a structural and phylogenetic point of view.

Gemcitabine (2', 2'-difluorodeoxycytidine; dFdC) is a deoxycytidine analog and is used primarily against pancreatic cancer. The cytotoxicity of gemcitabine is due to the inhibition of DNA replication. However, a mechanism of removal of the incorporated dFdC is largely unknown. In this report, we discovered that nucleotide excision repair protein XPF-ERCC1 participates in the repair of gemcitabine-induced DNA damage and inactivation of XPF sensitizes cells to gemcitabine. Further analysis identified that XPF-ERCC1 functions together with apurinic/apyrimidinic endonuclease (APE) in the repair of gemcitabine-induced DNA damage. Our results demonstrate the importance of the evaluation of DNA repair activities in gemcitabine treatment.

Fireflies and their luminous courtships have inspired centuries of scientific study. Today firefly luciferase is widely used in biotechnology, but the evolutionary origin of bioluminescence within beetles remains unclear. To shed light on this long-standing question, we sequenced the genomes of two firefly species that diverged over 100 million-years-ago: the North American Photinus pyralis and Japanese Aquatica lateralis. To compare bioluminescent origins, we also sequenced the genome of a related click beetle, the Caribbean Ignelater luminosus , with bioluminescent biochemistry near-identical to fireflies, but anatomically unique light organs, suggesting the intriguing hypothesis of parallel gains of bioluminescence. Our analyses support independent gains of bioluminescence in fireflies and click beetles, and provide new insights into the genes, chemical defenses, and symbionts that evolved alongside their luminous lifestyle., Competing Interests: TF, SL, CC, MB, GM, AB, MB, HD, IW, JD, AS, CS, KS, DH, RS, DN, SL, SS, SB, AL, YO, JW No competing interests declared, (© 2018, Fallon et al.)

Thrombopoietin (TPO) is a critical regulator of hematopoiesis. We previously reported that a severe aplastic anemia (SAA) who received a short-term administration of pegylated recombinant human megakaryocyte growth and development factor (rHuMGDF). A trilineage hematologic response was induced, however the patient was diagnosed with leukemia after nine years and eight months from administration of rHuMGDF. In recent reports, somatic mutations in myeloid cancer candidate genes were present in one-third of the AA. A mutant clone may be expanded by rHuMGDF in our patient. The long-term safety of patients treated with TPO and eltrombopag remains unknown. Careful observations are warranted hereafter.

Blood glucose levels fluctuate considerably in diabetic patients with reduced secretion of endogenous insulin. We previously reported that glucagon is secreted excessively in these patients and that taurine increases glucagon secretion in vitro. Therefore, we hypothesized that glucose tolerance would further deteriorate when taurine was administered to diabetic mice incapable of insulin secretion. We generated four groups of streptozotocin (STZ)-treated C57BL/6J mice (STZ-mice): STZ-mice without taurine treatment (STZ-Con), STZ-mice treated with 0.5% (w/v) taurine (STZ-0.5% Tau), STZ-mice treated with 1% (w/v) taurine (STZ-1% Tau), and STZ-mice treated with 2% (w/v) taurine (STZ-2% Tau). Mice were treated for 4 weeks, and then, we evaluated glucose tolerance, pancreatic β-cell area and α-cell area, pancreatic insulin and glucagon content, and daily blood glucose variability. As a result, following the administration of taurine, glucose tolerance improved, both pancreatic β- and α-cell area increased, and both insulin and glucagon content increased. In the 1% taurine administration group, blood glucose variability decreased. These unexpected results suggest that taurine improves glucose tolerance, in spite of its subsequent increased glucagon production, partly by increasing pancreatic β-cells and insulin production in vivo., Competing Interests: All institutional and national guidelines for the care and use of laboratory animals were followed.TH. has received honoraria from Novo Nordisk Pharma for lectures. A.I. has received honoraria from Eli Lilly Japan for lectures. Y.N., Y.M–M., M.B-T., and J.T. declare that they have no conflict of interest.

Nocturnal Japanese fireflies, Luciola parvula, emit from their lanterns a yellow light, one of the most red-shifted colors found among fireflies. Previously, we isolated and characterized two different types of luciferase gene, Luc1 and Luc2, from the fireflies Luciola cruciata and Luciola lateralis; Luc1 is responsible for the green-yellow luminescence of larval and adult lanterns, whereas Luc2 is responsible for the dim greenish glow of eggs and pupal bodies. The biological role of firefly lanterns in adults is related to sexual communication, but why the eggs and pupae glow remains uncertain. In this study, we isolated the gene Luc2 from L. parvula, and compared its expression profiles and enzymatic characteristics with those of Luc1. A semi-quantitative reverse transcription polymerase chain reaction showed that Luc1 was predominantly expressed in larvae, prepupae, pupae and adults, whereas Luc2 was expressed in eggs, prepupae, pupae and adult females. Enzymatic analyses showed that the luminescent color of Luc1 matches the visual sensitivity of L. parvula eyes, whereas that of Luc2 is very different from it. These results suggest that the biological role of Luc2 expressed in immobile stages is not intraspecific communication., (Copyright © 2017 John Wiley & Sons, Ltd.)

Two paralogous genes of firefly luciferase, Luc1 and Luc2, have been isolated from the species in two subfamilies, Luciolinae and Photurinae, of the family Lampyridae. The gene expression profiles have previously been examined only in the species of Luciolinae. Here we isolated Luc1 and Luc2 genes from the Japanese firefly Pyrocoelia atripennis. This is the first report of the presence of both Luc1 and Luc2 genes in the species of the subfamily Lampyrinae and of the exon-intron structure of Luc2 in the family Lampyridae. The luminescence of both gene products peaked at 547 nm under neutral buffer conditions, and the spectrum of Luc1, but not Luc2, was red-shifted under acidic conditions, as observed for Luc2 in the Luciolinae species. The semi-quantitative reverse transcription-polymerase chain reaction suggested that Luc1 was expressed in lanterns of all the stages except eggs, while Luc2 was expressed in the non-lantern bodies of eggs, prepupae, pupae, and female adults. These expression profiles are consistent with those in the Luciolinae species. Considering the distant phylogenetic relationship between Lampyrinae and Luciolinae in Lampyridae, we propose that fireflies generally possess two different luciferase genes and the biochemical properties and gene expression profiles for each paralog are conserved among lampyrid species.

Progression of anemia in patients with chronic kidney disease (CKD) is associated with an increased risk of death and hospitalization. It is not sufficiently clear whether treating renal anemia with recombinant human erythropoietin (rHuEPO) has a beneficial effect on early survival after hemodialysis (HD) initiation in patients with CKD. The study was an open-label multicenter retrospective cohort study to evaluate the relationship between rHuEPO treatment and early survival after HD initiation in patients with CKD. Predialysis patients with CKD were divided into two groups: an rHuEPO-treated group (rHuEPO group) and a non-treatment group. The primary endpoint was all-cause mortality in the year after HD initiation. A total of 3261 patients were enrolled (2275 in the rHuEPO group and 986 in the non-treatment group). One-year survival was 95.36% in the rHuEPO group and 90.36% in the non-treatment group. The survival rate was significantly higher in the rHuEPO group (P < 0.0001). The results of multivariate analysis confirmed that predialysis treatment with rHuEPO is a predictor for reduced mortality risk (hazard ratio = 0.61, 95% confidence interval: 0.42-0.87, P = 0.006). Risk for the composite event of death/hospitalization was also lower in the rHuEPO group (hazard ratio = 0.88, 95% confidence interval: 0.78-0.98, P = 0.026). The results of this study suggest that treatment with rHuEPO can decrease early mortality risk after initiation of HD in patients with CKD. A prospective study is needed to further investigate early survival after HD initiation., (© 2016 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

Background: The significance of HBV reactivation during immunosuppressive therapy was evaluated in three nationwide cohorts including patients with previously resolved HBV (prHBV) infection., Methods: The clinical features of 1061 patients with acute liver failure (ALF) or late-onset hepatic failure (LOHF) were retrospectively examined, focusing on those who experienced HBV reactivation. Additionally, 420 patients with prHBV infection were prospectively enrolled: 203 received immunosuppressive therapies immediately after enrollment, while the remaining 217 were enrolled after having received immunosuppressive therapies without the occurrence of HBV reactivation. The serum HBV-DNA levels were prospectively monitored every month, and the incidences of HBV reactivation, defined as a serum HBV-DNA level of 1.3 log IU/ml or more, were evaluated., Results: In the retrospective study, persistent HBV infection was found in 90 patients, and HBV reactivation was responsible for liver injuries in 50 patients including 23 receiving immunosuppressive therapies (26 with HBs-antigen positivity, 7 with prHBV infection). None of seven patients with prHBV infection were rescued. In the prospective studies, HBV reactivation occurred in ten patients, but preemptive entecavir administration prevented liver injury. The cumulative reactivation rate was 3.2 % at 6 months, and the increase of the rate compared to that at 6 months was +1.5 % at 48 months., Conclusions: HBV reactivation during immunosuppression was responsible for liver injuries in a quarter of the ALF/LOHF patients with persistent HBV infection. Early serum HBV-DNA monitoring may improve patient prognosis, since HBV reactivation typically occurs within 6 months of the start of immunosuppressive therapies in patients with prHBV infection.

The percentage manifesting dysplasia in bone marrow needed to qualify as significant is ≥10 % in each lineage. However, detailed analyses of this threshold have not been reported. Here, we analyzed dyserythropoiesis (dysE) in 109 myelodysplastic syndromes (MDS) patients with 21 immune thrombocytopenia (ITP)/12 hemolytic anemia (HA) patients as a control. In present study, mild megaloblastic erythroblasts were specifically named 'red cell with abnormal chromatin clumping (RCACC)'. RCACC ≥10 % in erythroblasts was observed in 29 % of ITP patients and 58 % of HA patients. The numbers of MDS patients with RCACC in erythroblasts <10, 10-19 and ≥20 % were 1, 3, and 105, respectively. We analyzed dysE criteria according to the WHO classification (original WHO dysE). Most of our MDS patients (98 %) had original WHO dysE ≥20 %. The ITP patients with original WHO dysE ≥10 % was 48 %, and there were no ITP patients had original WHO dysE ≥20 %. Sixty-seven percent of HA patients had original WHO dysE ≥10 %, and three patients (25 %) had original WHO dysE ≥20 %. Raising the threshold of the original WHO dysE from 10 to 20 or 30 % may provide more suitable criteria. If RCACC is not included in dysE criteria, we think that '10 %' is a suitable threshold for the determination of dyserythropoiesis.

Objectives: We investigated the effect of cartilage degeneration on ultrasound speed in human articular cartilage in vitro., Methods: Ultrasound speed was calculated by the time-of-flight method for 22 femoral condyle osteochondral blocks obtained from osteoarthritis patients. In parallel, histological evaluation of specimens was performed using the modified Mankin and OARSI scores., Results: The mean ultrasound speed was 1757 ± 109 m/s. Ultrasound speed showed significant negative correlation with OARSI score, and a decreasing tendency with high Mankin scores. Good correlation was found between the optically measured and the calculated cartilage thickness., Conclusion: Our results show that articular cartilage degeneration has relatively little influence on ultrasound speed. In addition, morphological evaluation of articular cartilage using a preset value of ultrasound speed seems to offer relatively accurate results.

Objective: The objective of this study was to investigate the factors that affect the predicted bone strength of proximal femur in Japanese population., Methods: Participants (552 men and 273 women) in a health checkup program with computed tomography (CT) at the University of Tokyo Hospital were enrolled in this study. Three-dimensional finite element models of the proximal femur were constructed from CT data of the participants with simultaneous scans of a calibration phantom containing hydroxyapatite rods. Multiple regression analysis was performed to analyze the relationship between the predicted bone strength and clinical factors., Results: Average predicted strength of proximal femur was lower in women than in men in all age ranges. Predicted bone strength in women under both stance and fall configurations significantly decreased with age, and that in men had the tendency to decrease with age. Body weight positively affected the predicted bone strength in both men and women., Conclusions: This is the first cross-sectional analysis of the predicted bone strength of the proximal femur in Japanese population of wide age range. Age and body weight critically affected bone strength of proximal femur determined by quantitative CT-based finite element method, in particular in women, under both stance and fall configurations.

A number of studies have addressed the environmental temperatures experienced by ancient life. Computational studies using a nonhomogeneous evolution model have estimated ancestral G + C contents of ribosomal RNAs and the amino acid compositions of ancestral proteins, generating hypotheses regarding the mesophilic last universal common ancestor. In contrast, our previous study computationally reconstructed ancestral amino acid sequences of nucleoside diphosphate kinases using a homogeneous model and then empirically resurrected the ancestral proteins. The thermal stabilities of these ancestral proteins were equivalent to or greater than those of extant homologous thermophilic proteins, supporting the thermophilic universal ancestor theory. In this study, we reinferred ancestral sequences using a dataset from which hyperthermophilic sequences were excluded. We also reinferred ancestral sequences using a nonhomogeneous evolution model. The newly reconstructed ancestral proteins are still thermally stable, further supporting the hypothesis that the ancient organisms contained thermally stable proteins and therefore that they were thermophilic., (© 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.)

Immunosuppressive therapy has been employed as the initial treatment for acquired chronic pure red cell aplasia (PRCA), such as idiopathic, thymoma-associated, or large granular lymphocyte (LGL) leukaemia-associated PRCA, which is thought to be immune-mediated. To explore the overall long-term outcome following immunosuppression and to identify the risk factors for death in these disorders, we conducted nationwide surveys in Japan 2004 and 2006, and identified a total of 185 patients with acquired chronic PRCA, including 72 idiopathic, 41 thymoma-associated and 14 LGL leukaemia-associated cases of PRCA for whom data was available. The present study evaluated 127 patients with these three subsets of PRCA. The median overall survival has not yet been reached in idiopathic PRCA. The estimated median overall survival times in patients with thymoma-associated and LGL leukaemia-associated PRCA were 142·1 and 147·8 months, respectively. Twenty-two deaths were reported, and the response to induction therapy and relapse of anaemia were found to be associated with death. The major causes of death were infection in seven patients and organ failure in another seven patients. The results suggest that maintenance therapy and the management of infectious complications are crucial for improving the prognosis of chronic PRCA., (© 2015 John Wiley & Sons Ltd.)

We fabricated a transparent nonfibrillar collagen gel using gamma irradiation (5 kGy) and cultured rat mesenchymal stem cells (MSCs) on both the gamma-irradiated collagen gel and on unirradiated fibrillar collagen gel. Cells attached well and proliferated with high viability on the surface of both gels. The cells cultured on the gamma-irradiated nonfibrillar gel had a unique elongated shape and adhered to each other in culture. After 21 days of culture in dexamethasone-containing culture medium, the contents of bone-specific osteocalcin and calcium on the gamma-irradiated nonfibrillar gel were 1.4 and 1.9 times higher than those on fibrillar collagen gel, respectively. These data show that osteogenic differentiation of MSCs was promoted more efficiently on the gamma-cross-linked nonfibrillar gel than on the fibrillar gel and demonstrate the potential of the gamma-irradiated collagen gel for use in bone tissue engineering., (Copyright © 2014 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.)

Glycemic instability is a serious problem in patients with insulin-deficient diabetes, and it may be due in part to abnormal endogenous glucagon secretion. However, the intracellular metabolic mechanism(s) involved in the aberrant glucagon response under the condition of insulin deficiency has not yet been elucidated. To investigate the metabolic traits that underlie the distortion of glucagon secretion under insulin deficient conditions, we generated an αTC1-6 cell line with stable knockdown of the insulin receptor (IRKD), i.e., an in vitro α-cell model for insulin-deficient diabetes, which exhibits an abnormal glucagon response to glucose. A comprehensive metabolomic analysis of the IRKD αTC1-6 cells (IRKD cells) revealed some candidate metabolites whose levels differed markedly compared to those in control αTC1-6 cells, but also which could affect the glucagon release in IRKD cells. Of these candidates, taurine was remarkably increased in the IRKD cells and was identified as a stimulator of glucagon in αTC1-6 cells. Taurine also paradoxically exaggerated the glucagon secretion at a high glucose concentration in IRKD cells and islets with IRKD. These results indicate that the metabolic alterations induced by IRKD in α-cells, especially the increase of taurine, may lead to the distorted glucagon response in IRKD cells, suggesting the importance of taurine in the paradoxical glucagon response and the resultant glucose instability in insulin-deficient diabetes.

Although erythropoiesis-stimulating agents (ESAs) are effective at treating anemia, the association between hemoglobin (Hb) levels and survival is still unclear, especially for the incident Japanese hemodialysis (HD) population. The Japan Erythropoietin Treatment (JET) Study is an open multi-center, prospective, observational study designed to evaluate the relationship between the maintenance of Hb levels and new HD patient prognosis after the first administration of epoetin beta. Landmark analyses were performed to examine the relationship between Hb levels at 6 months and survival. Among a total of 10,310 patients, 6631 completed the initial 6 months of epoetin beta treatment (induction phase) and were followed up for a further 2.5 years (maintenance phase). Three-year survival rate of patients with <9 g/dL Hb levels after 6 months was 74.1%, which was significantly lower than 89.3% for patients with Hb levels 10 to 11 g/dL; the adjusted hazard ratio (HR) was 2.08 (95% CI, 1.57-2.77; P < 0.0001). Moreover, the 3-year survival rate for poor responders defined by Hb levels <10 g/dL and weekly epoetin beta doses ≥ 9000 IU during the induction phase was 71.6%, which was significantly lower than 89.4% for the group, which had Hb levels 10 to 11 g/dL excluding poor responders and those with excursion; the HR was 1.71 (95% CI, 1.13-2.60; P = 0.0118). Adverse events related to the treatment were reported in 71 of 10,310 patients (0.69%). These findings suggest that the achieved low Hb levels and poor response to ESA therapy are significantly associated with high mortality., (© 2014 The Authors. Therapeutic Apheresis and Dialysis © 2014 International Society for Apheresis.)

Background: The serum cytokeratin-18 fragment (CK-18) concentration has been suggested to be a biomarker of nonalcoholic fatty liver disease (NAFLD), although its usefulness in patients with type 2 diabetes mellitus (T2DM) is unknown., Methods: The study was divided into two parts. In the first cross-sectional study, a total of 200 patients with T2DM and 58 healthy control subjects were recruited. NAFLD was diagnosed using ultrasonography. In the subsequent longitudinal study, we evaluated the three-month change (Δ) in the CK-18 concentration and other parameters in 40 T2DM patients with NAFLD., Results: The serum CK-18 values were significantly higher in the NAFLD group than in the nonNAFLD group among both diabetic and nondiabetic subjects. The CK-18 concentration was found to be an independent determinant of NAFLD and was positively correlated with the ultrasonography score and AST and ALT concentrations in the T2DM patients. Positive correlations were also identified between the CK-18 and transaminase concentrations in the T2DM and NAFLD cohorts. ΔCK-18 was found to be significantly associated with ΔBMI in the T2DM patients with NAFLD., Conclusions: A dose effect between the CK-18 concentration and the severity of NAFLD was found in the T2DM patients; thus, the CK-18 concentration is a potentially useful biomarker for assessing the efficacy of treatment and the improvement in NAFLD in patients with T2DM., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Myelodysplastic syndromes with myelofibrosis (MDS-F) is a poor prognostic hematopoietic disorder. Azacitidine was shown to prolong survival of high-risk MDS patients. However, the effects of azacitidine on MDS-F have yet to be elucidated. Azacitidine was administered to a 74-year-old man with MDS-F at a dose of 75 mg/m(2)/daily subcutaneously for 7 days every 28 days. Hematologic improvements were observed according to the International Working Group 2006 criteria after 8 cycles of the azacitidine treatment, and complete remission was achieved after 14 cycles. The grade of myelofibrosis was also improved. The therapeutic activity of azacitidine was confirmed in our MDS-F patient.

The effect of recombinant human erythropoietin (rHuEPO) treatment on the progression of chronic kidney disease (CKD) has not been fully evaluated in Japan. We therefore retrospectively evaluated this in a sub-cohort of a prospective multicenter study to investigate optimal hemoglobin (Hb) level of CKD patients on hemodialysis (HD) treated with rHuEPO; Japan Erythropoietin Treatment Study for Target Hb and Survival (JET study). Effect of rHuEPO treatment during predialysis period to delay initiation of HD was retrospectively assessed in 2434 patients from the JET study comparing groups with and without rHuEPO treatment. The assessment was done by Cox proportional hazards regression analysis and inverse probability-weighted (IPW) analysis to adjust for time-dependent confounders. The weights used in the IPW analysis were calculated using a logistic model that included baseline confounders and time-dependent variables. During the predialysis period, 71.7% (1746 patients) were treated with rHuEPO (mean Hb level of 8.7 g/dL at initiation of rHuEPO treatment). Covariates significantly associated with initiation of rHuEPO treatment were Hb level, serum creatinine level, age, diabetes, cardiac insufficiency, and hypertension. The adjusted hazard ratio for time until HD initiation under rHuEPO treatment was 0.272 (95% CI, 0.223-0.331; P < 0.001) in the Cox analysis and 0.63 (95% CI, 0.53-0.76; P < 0.0001) in the IPW analysis. This retrospective study suggests that rHuEPO treatment during the predialysis period has preventive effects on the progression of CKD although further prospective investigation on the efficacy is needed., (© 2013 The Authors. Therapeutic Apheresis and Dialysis © 2013 International Society for Apheresis.)

We investigated the association between arginine-stimulated glucagon secretion (AUCIRG) and several parameters of glycaemic variability in 12 patients with type 1 diabetes without residual beta-cell function. AUCIRG positively correlated with the SD and mean amplitude of glycaemic excursions, thus glucagon might contribute to glycaemic instability, independent of endogenous insulin., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

The purpose of this study is to examine the molecular mechanism underlying the toxicity of arsenic trioxide (ATO) in cardiac cells. H9c2 rat cardiomyoblastoma cells undergo apoptosis during exposure to the concentrations of ATO > 10 μM for 24 h. The process is accompanied by the activation of caspases and is suppressed by the pan-caspase inhibitor z-VAD. Since ATO-induced H9c2 cell death is suppressed by Rho-kinase (ROCK) inhibitor Y-27632, but not by any antioxidants tested, apoptosis by ATO seems to be initiated through a ROCK-dependent and reactive oxygen species-independent mechanism. During the execution of apoptosis by ATO, the induction of autophagy is also observed. Importantly, autophagy is accelerated in cells treated with ATO plus Y-27632, although Y-27632 alone does not induce autophagy. The cytoprotective effect of Y-27632 against ATO toxicity is abrogated by the co-administration of an autophagy inhibitor, 3-methyladenine, suggesting that autophagy contributes to the cytoprotection by Y-27632. Taken together, the data indicate that the activation of ROCK is required for apoptotic H9c2 cardiomyoblastoma cell death by ATO, and that the ROCK inhibition not only inhibits caspase-dependent apoptotic machinery, but also causes a rise in the cytoprotective autophagy processes during ATO exposure.

Objectives: To analyze the correlation between dysplastic lineage and type of cytopenia in myelodysplastic syndromes., Methods: We analyzed the correlation between dysplasia and cell count using the data set of our previous morphologic study., Results: There were no correlations between dysgranulopoiesis of 10% or more and absolute neutrophil count (ANC). Similarly, hyposegmented mature neutrophils (Pelger) of 10% or more were not related to ANC. Interestingly, the platelet count of patients with dysmegakaryopoiesis (dys Mgk) was higher than that of patients without dys Mgk (dys Mgk ≥10% vs <10%, P = .08; dys Mgk ≥40% vs <40%, P = .02; micromegakaryocytes ≥10% vs <10%, P = .004)., Conclusions: Since low cell counts did not correlate with the presence of dysplastic features, we suggest that dysplastic features do not directly relate to apoptosis.

Poly(ADP-ribose) polymerase (PARP), an enzyme that is important to the regulation of nuclear function, is activated by DNA strand breakage. In massive DNA damage, PARP is overactivated, exhausting nicotinamide adenine dinucleotide and leading to cell death. Recent studies have succeeded in reducing cellular damage in ischemia/reperfusion by inhibiting PARP. However, PARP plays an important part in the DNA repair system, and its inhibition may be hazardous in certain situations. We compared the short-time inhibition of PARP against continuous inhibition during ischemia/reperfusion using isolated rat hearts. The hearts were reperfused after 21 minutes of ischemia with a bolus injection of 3-aminobenzamide (3-AB) (10 mg/kg) followed by continuous 3-AB infusion (50 μM) for the whole reperfusion period or for the first 6 minutes or without 3-AB. At the end of reperfusion, contractile function, high-energy phosphate content, nicotinamide adenine dinucleotide content, and infarcted area were significantly preserved in the 3-AB 6-minute group. In the 3-AB continuous group, these advantages were not apparent. At the end of reperfusion, PARP cleavage had significantly proceeded in the 3-AB continuous group, indicating initiation of the apoptotic cascade. Thus, continuous PARP inhibition by 3-AB does not reduce reperfusion injury in the isolated rat heart, which may be because of acceleration of apoptosis.

Conventional surgical navigation requires for surgeons to move their sight and conscious off the surgical field when checking surgical tool's positions shown on the display panel. Since that takes high risks of surgical exposure possibilities to the patient's body, we propose a novel method for guiding surgical tool position and orientation directly in the surgical field by a laser beam. In our navigation procedure, two cross-sectional planar laser beams are emitted from the two laser devices attached onto both sides of an optical localizer, and show surgical tool's entry position on the patient's body surface and its orientation on the side face of the surgical tool. In the experiments, our method gave the surgeons precise and accurate surgical tool adjusting and showed the feasibility to apply to both of open and percutaneous surgeries.

We isolated cDNA for a luciferase isotype, LlLuc2, from the ovary of the Japanese firefly, Luciola lateralis. The gene product LlLuc2 showed 59% amino acid identity with LlLuc1, which had been isolated from the adult L. lateralis lantern. Molecular phylogenetic analysis indicated that LlLuc2 is an orthologue of LcLuc2 from Luciola cruciata. The spectral maxima of the luminescence by recombinant LlLuc1 and LlLuc2 were 550 and 539 nm, respectively. Quantitative PCR analysis revealed that LlLuc1 was expressed predominantly in larvae and adults, and LlLuc2 was expressed in eggs and pupae, which glow dimly, and we found that the in vivo luminescence spectra of the egg and pupa in L. lateralis were in good agreement with the in vitro luminescence spectrum by LlLuc2. These results suggest that, in L. lateralis, LlLuc1 is responsible for the yellowish luminescence of larval and adult lanterns, and LlLuc2 is responsible for the dim, greenish glow of eggs and whole pupae. Similar results were obtained in L. cruciata.

A 64-year-old male was found dead in his house with his face covered with blood and a 38-caliber revolver between his legs. He had been suffering from type 2 diabetes mellitus and aftereffects of cerebral infarction. Autopsy revealed a normal round contact wound in the left lateral cervical region. A bullet from the firearm had entered through the left lateral cervical region and traveled to the outer right sternocleidomastoid muscle. This also triggered another wound from the fifth cervical vertebra to the muscle tissue near the right cartilage thyroid. At the end of this channel, there were three bone fragments. Here, we report this interesting case with two channels caused by a bullet and by a resulting bone fragment. We also discuss the characteristics of an ear lobe injury found on the victim and show how this injury and blood and skin on the revolver were used as clues to determine the posture at the time of the shot., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: It has been previously demonstrated that low-intensity pulsed ultrasound stimulation (LIPUS) enhances formation of the medullary canal and cortex in a gap-healing model of the tibia in rabbits, shortens the time required for remodeling, and enhances mineralization of the callus. In the current study, the mechanical integrity of these models was confirmed. In order to do this, the cross-sectional moment of inertia (CSMI) obtained from quantitative micro-computed tomography scans was calculated, and a comparison was made with a four-point bending test., Methods: This parameter can be analyzed in any direction, and three directions were selected in order to adopt an XYZ coordinate (X and Y for bending; Z for torsion)., Results: The present results demonstrated that LIPUS improved earlier restoration of bending stiffness at the healing site. In addition, LIPUS was effective not only in the ultrasound-irradiated plane, but also in the other two planes., Conclusions: CSMI may provide the structural as well as compositional determinants to assess fracture healing and would be very useful to replace the mechanical testing.

About 5-10 % of chronic myelogenous leukemia (CML) patients show variant Philadelphia (Ph) translocations. The formation mechanisms and clinical significance of variant Ph translocations remain unclear. We report a CML case with a novel five-way complex translocation. Although the result of initial G-banding was 46,XY,t(7;11;9)(q22;q13;q34),t(9;22)(q34;q11.2), fluorescence in situ hybridization (FISH) demonstrated t(7;11;9;22;9)(q22;q13;q34;q11.2;q34) consisting of sequential rearrangements involving five chromosomes. The patient was successfully treated by imatinib and obtained a major molecular response. To our knowledge, this is the tenth CML case with a complicated Ph translocation involving five chromosomes and the third one treated by imatinib. Good response with imatinib therapy suggested that a single-event rearrangement was involved in the chromosomal changes.

In 114 patients with monoclonal gammopathy of undetermined significance (MGUS) followed-up in Tachikawa Sougo hospital, we retrospectively analyzed progression of their disease to multiple myeloma (MM) or related disorders. The analysis was based on a total of 1,170 person-years of follow-up in a cohort with a median age at diagnosis of MGUS of 68 years 3 months, and with a median follow-up period of 9 years 5 months. Of these 114 patients, 13 (11%) showed progression to MM or related disorders with a median time to progression of 9 years 4 months; and the median age of these 13 patients was 78 years 8 months. The cumulative hazard ratio of progression at 5, 10, 15, and 20 years after diagnosis was 3.0%, 9.0%, 11.4%, and 32.1%, respectively. The risk of progression of MGUS to MM or related disorders in Japanese patients was as high as in Western patients studied previously, demonstrating that MGUS should be carefully monitored as a preneoplastic condition.

The present study aimed to develop a method to measure three-dimensional (3-D) thickness of cartilage (Tc) at the femoral condyle using B-mode ultrasonography (US) and to clarify the feasibility of US in clinical evaluations of articular cartilage by comparing the results with 3-D measurement values using magnetic resonance imaging (MRI) and assessing repeatability. The medial surface of the right knees of two healthy male volunteers (age, 37 and 59 years) and the knees on affected side of three male patients with osteoarthritis (OA) (age, 73, 81 and 83 years) were scanned using B-mode US with the knee flexed at 120°. The range of the angle of probe rotation for the arm was 0-80° and B-mode images (total, 101 images) were acquired every 0.8°. MRI of the knees was also performed using the double echo steady-state sequence. Both US and MRI images were used to create 3-D models of medial femoral condyle articular cartilage. Tc was determined at points 1 mm apart from one another in the US model (Tc-US) and MRI model (Tc-MRI). Tc-US was compared with Tc-MRI and the repeatability of Tc-US was assessed by mean Tc in the specific region of interest of the femoral condyle. Tc-US correlated significantly with Tc-MRI both in volunteers and in OA patients (p < 0.0001 each) and coefficients of correlation were 0.976 and 0.964 for volunteers and OA patients, respectively. The coefficient of variance for mean Tc-US was 4.90%. Our results show that 3-D US measurements of femoral cartilage are reproducible and correlate strongly with MRI measurements., (Copyright © 2012 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

A 37-year-old female who presented with pancytopenia in April 2008 was diagnosed with aplastic anemia stage 2 with a normal karyotype. She had a PNH phenotype in her red blood cells (RBC) and granulocytes, and HLA DR15. Her aplastic anemia was deteriorated from stage 2 to stage 3, and she required periodic RBC transfusions. Four months after cyclosporine therapy, the pancytopenia improved and she did not need RBC transfusion. However, three months thereafter, she again required RBC transfusions after developing severe ulcerative colitis. Although mesalazine and steroid pulse therapy improved her ulcerative colitis, her transfusion dependency persisted. Eleven months after the diagnosis of aplastic anemia, equine anti-thymocyte globulin (ATG) and cyclosporine were administered, but no hematological improvement was obtained. Six months after the administration of ATG and cyclosporine, transformation to refractory cytopenia with multilineage dysplasia (RCMD) with 7-monosomy was observed. An allogeneic bone marrow transplant (BMT) from a HLA-identical sibling was performed 23 months after the diagnosis of aplastic anemia. Complete remission of both the aplastic anemia and ulcerative colitis was obtained without medication. Although the relationship between aplastic anemia and ulcerative colitis remains unclear, immunological abnormalities might be involved in the pathogenesis of both disorders because she had PNH phenotype in RBC and HLA DR15 and because allogeneic BMT improved both disorders.