A pharmacovigilance study on clinical factors of active vitamin D analog-related acute kidney injury using the Japanese Adverse Drug Event Report Database.

Acute kidney injury (AKI) due to vitamin D therapy for osteoporosis is encountered in clinical practice, but epidemiological studies are scarce. We aimed to determine the association between AKI and vitamin D therapy and to identify risk factors for AKI using the Japanese Adverse Drug Event Report database. We used reporting odds ratios (RORs) to detect signals and evaluate risk factors using multiple logistic regression analysis.

Design, Construction, and Validation of Targeted Gene Activation with TREE System in Human Cells.

Genome editing technologies can be diverted into artificial transcription activators. In particular, researchers have improved dCas9-based technologies by tandem-fusing or trans-accumulating effector domains. Previously, we developed a hierarchical effector accumulation system named "TREE," enabling robust activation of target genes even when strongly silenced.

Various strategies of effector accumulation to improve the efficiency of genome editing and derivative methodologies.

CRISPR-Cas9 is a sophisticated tool in which Cas9/sgRNA complexes bind to the programmed target sequences and induce DNA double-strand breaks (DSBs) enabling highly efficient genome editing. Moreover, when nuclease-inactive Cas9 (dCas9) is employed, its specific DNA-binding activity provides a variety of derivative technologies such as transcriptional activation/repression, epigenome editing, and chromosome visualization. In these derivative technologies, particular effector molecules are fused with dCas9 or recruited to the target site.

Three-Component Repurposed Technology for Enhanced Expression: Highly Accumulable Transcriptional Activators via Branched Tag Arrays.

In the past few years, several types of artificial transcriptional activator, based on CRISPR-Cas9, have been developed and refined. Of these, in synergistic activation mediator and SunTag systems, the effector proteins, expressed in , can be recruited to the target sites via the MS2 RNA-binding system and GCN4-scFv antibody system, respectively. Here, we report a strong transcriptional activation system achieved by fusing GCN4 repeat to MS2 coat protein to accumulate numbers of activators, fused to scFv antibodies.

Biased genome editing using the local accumulation of DSB repair molecules system.

Selective genome editing such as gene knock-in has recently been achieved by administration of chemical enhancer or inhibitor of particular DNA double-strand break (DSB) repair pathways, as well as overexpression of pathway-specific genes. In this study, we attempt to enhance the efficiency further to secure robust gene knock-ins, by using the local accumulation of DSB repair molecules (LoAD) system. We identify CtIP as a strong enhancer of microhomology-mediated end-joining (MMEJ) repair by genetic screening, and show the knock-in-enhancing effect of CtIP LoADing.

Sensitive colorimetric assay of serum diamine oxidase.

A simple and sensitive colorimetric assay for serum diamine oxidase (DAO) activity was based on a coupled reaction with peroxidase and a new chromogen, 10-(carboxymethyl-aminocarbonyl)-3,7-bis(dimethylamino) phenothiazine sodium salt (DA-67). In the presence of peroxidase and DA-67, peroxidase catalyzes the formation of methylene blue having an absorption maximum at 668 nm. The proposed method eliminates the interferences occurring in serum with use of ascorbate oxidase and stops the reaction with sodium diethyldithiocarbamate, leaving the methylene blue in the reaction mixture stable for about 2 h.

T-cell malignancy following B-cell lymphoma in remission.

A T-cell malignancy developed in a 64-year-old man with recurrent B-cell lymphoma after one and a half years of remission. Immunophenotypic and DNA analyses confirmed clonality and cell lineage of both lymphoid malignancies. Sequential development of B- and T-cell malignancies in this patient may be an example of biclonal lymphoma or treatment-related secondary lymphoma.

Peripheral T-cell lymphoma: clinicopathologic analyses of 25 cases.

Twenty-five patients with peripheral T-cell lymphoma (PTCL) were analyzed to assess clinicopathologic features of the disease and were classified according to the newly proposed histologic classification for T-cell lymphomas to study the correlation between histology and survival, if any. Histologic diagnoses were: Lennert's, 1; T-zone, 1; pleomorphic, small, 1; pleomorphic, large, 1; angiocentric, 4; pleomorphic, medium, 5; immunoblastic, 5; angioimmunoblastic, 7. Patients with PTCL were noted to be endowed with clinicopathologic factors known to adversely affect survival, such as advanced stage (92%), B symptoms (56%), liver involvement (56%), multinodal disease (52%), elevated serum LDH (48%), and so on.

T-cell phenotype is associated with decreased survival in non-Hodgkin's lymphoma.

This study was undertaken to determine which if any pretreatment factors are statistically significant determinants of the clinical outcome in patients with non-Hodgkin's lymphoma. The pretreatment factors in 20 patients with T-cell lymphoma, including two patients with adult T-cell leukemia/lymphoma (ATLL), and 28 patients with B-cell lymphoma were evaluated. In a stepwise logistic regression analysis, a T-cell phenotype in addition to high grade histology and pleural involvement demonstrated a statistically significant correlation with decreased response rate, when the analysis did not include patients with ATLL.

[Clinicopathologic analyses of eleven patients with Hodgkin's disease].

Clinicopathologic analyses were performed on 11 patients with histopathologic diagnosis of Hodgkin's disease which was confirmed immunohistochemically with the use of anti-Leu M 1 which is known to be specific to Reed-Sternberg cells. Patients with clinical stage II developed infradiaphragmatic involvement after Mantle field irradiation and should have been treated with extended field irradiation or combined modality therapy because of the possibility of PSIII1. Maintenance VENP therapy seemed to sustain remission but may have caused opportunistic infections.

Weekly CHOP for the treatment of advanced intermediate and high-grade non-Hodgkin's lymphoma.

Between January 1981 and September 1986, 48 patients with advanced (stages III and IV) intermediate and high-grade non-Hodgkin's lymphoma (NHL) were treated with weekly CHOP (doxorubicin, vincristine, cyclophosphamide, and prednisolone), using reduced dosages of cyclophosphamide and doxorubicin. Low-dose oral maintenance chemotherapy was given for 2 years to those patients in remission. Twenty-seven patients (56%) of the evaluable 48 patients achieved a complete response and 12 patients (25%) had a partial response, for an overall response rate of 81%.

[Clinical analyses on 10 patients with follicular lymphoma].

Clinicopathologic analyses were done on 10 patients with follicular lymphoma including 8 patients with low grade malignancy. The complete response rate to chemo- and combined modality therapy was 80% with no deaths occurring in patients in complete remission with median follow-up of 73 months. The 5-years' survival for these 10 patients was 86%.

[Evaluation of the response of advanced diffuse large cell lymphomas (LSG classification) to weekly CHOP therapy].

"Weekly CHOP" therapy characterized by reduced dosages of cyclophosphamide, doxorubicin and vincristine, was evaluated in 33 patients with advanced diffuse large cell lymphomas (LSG classification). There were 19 complete responders (59%) and 8 partial responders (25%) with a response rate of 84%. A prolonged disease-free survival rate (survival plateau) of 60% was considered comparable to the results of second-generation chemotherapies.

[Clinical studies on eleven patients with nasal and paranasal lymphoma, with special reference to staging evaluation].

Adequacy of applying Ann Arbor classification and TNM classification to evaluate extent of disease in extranodal lymphoma was assessed in patients with nasal and paranasal lymphoma. Ann Arbor classification proposed to evaluate extent of Hodgkin's disease was not considered to be good at assessing extranodal local lesions. TNM classification was superior to Ann Arbor classification in terms of the correspondence with survival.

Relationship between immunophenotype and the development of second primary neoplasms in patients with non-Hodgkin's lymphoma.

We reviewed the records of 107 patients with non-Hodgkin's lymphoma (NHL) to evaluate the relation between second primary neoplasms and the NHL immunophenotype. The incidence of second primary neoplasms was 3.7%.

Bone marrow Ig-secreting cells in patients with malignant lymphoma.

Bone marrow immunoglobulin (Ig)-secreting cells of three major Ig classes were quantitated in patients with malignant lymphoma with or without definite bone marrow invasion, using a protein A hemolytic plaque assay. The mean percentage of each class of Ig-secreting cells in patients without bone marrow invasion was 77% for IgG, 17% for IgA, and 6% for IgM, whereas it was 86% for IgG, 6% for IgA, and 8% for IgM in patients with definite bone marrow invasion. An increase in bone marrow Ig-secreting cells of the same Ig class that is detected on the surface of lymphoma cells and that is consistent with the concentration of the same serum monoclonal Ig is considered to indicate the presence of metastatic lymphoma cells in the bone marrow.

Non-Hodgkin's lymphoma following Hodgkin's disease. A case report and immunohistochemical corroboration.

Two non-Hodgkin's lymphomas, one a follicular mixed cell type and the other a diffuse large cell type (Working Formulation), appeared 7 and 12 years, respectively, after the initial histopathologic diagnosis of Hodgkin's disease (nodular sclerosis) in an elderly male. The clinicopathologic implications of non-Hodgkin's lymphoma complicating Hodgkin's disease as a second malignant neoplasm are discussed on the basis of immunohistochemical studies performed on the sequentially biopsied lymph nodes using various monoclonal antibodies, in particular, anti-Leu-M1, which is known as a valuable marker of the neoplastic cells of Hodgkin's disease.

Quantification of ferritin-secreting cells in patients with non-Hodgkin's lymphoma.

Ferritin secretion in patients with hematological malignancies, particularly malignant lymphomas, were evaluated in terms of circulating ferritin-secreting cells (FSC). There was a positive correlation between the tumor cell mass and the number of FSC, particularly monocytic FSC, but lymphoma cell suspensions contained very few FSC in comparison with the expected number. These results indicate that lymphoma cells per se may not be responsible for ferritin synthesis and secretion and suggest that ferritin synthesis and secretion in the reticuloendothelial system may be increased as a nonspecific response.