pH response and mechanical properties of Fe2O3-TeO2-based glass/stainless steel enamel electrodes for pH sensors.

Glass pH sensors are unsuitable for in vivo biomedical, clinical, or food applications because of the brittleness of glass and the difficulty in measuring small volumes. Enamel structures such as glass/stainless steel are candidates for glass-based pH electrodes. In this study, new enamel electrodes for pH sensors using Fe2O3-TeO2-based glass/stainless steel were developed. The effect of NiO addition to Fe2O3-TeO2 glass on the pH sensitivity and the three-point bending strength of enamels were investigated. The effect of NiO addition to Fe2O3-TeO2 glass/stainless steel on the pH sensitivity was negligible. Fe2O3-TeO2-based glass/stainless steel showed pH sensitivity appropriate to a working electrode. Enameling at a lower temperature under an air atmosphere was desirable for narrowing the gap between pH 4-7 and pH 7-9 sensitivities. The NiO addition to Fe2O3-TeO2 glass/stainless steel decreased the three-point bending strength. Therefore, NiO did not serve as an adhesion oxide in the Fe2O3-TeO2 glass. Fe2O3-TeO2 glass/stainless steel possessed the highest three-point bending strength among all samples when prepared at 670 °C under an air atmosphere. Therefore, no NiO addition and enameling at a lower temperature under an air atmosphere are desirable for obtaining more robust Fe2O3-TeO2 glass/stainless steel than Li2O-SiO2-based glass electrodes for pH sensors.

[A case of mucosa-associated lymphoid tissue lymphoma of the bile duct diagnosed using intraductal ultrasonography and transpapillary investigation of the bile duct].

A 78-year-old woman with a chief complaint of mammary tumor was referred to our hospital and was diagnosed with mucosa-associated lymphoid tissue (MALT) lymphoma using needle biopsies. She presented with MALT lymphoma lesions in the stomach, duodenum, and intraperitoneal lymph nodes. Abdominal ultrasonography revealed thickened internal layer of the bile duct. Cholangiocarcinoma, immunoglobulin G4-related sclerosing cholangitis, and MALT lymphoma were suspected. She did not report any abdominal pain, and did not have jaundice. Endoscopic retrograde cholangiopancreatography and intraductal ultrasonography indicated diffuse, irregular wall thickening with the formation of nodule lesions in the extrahepatic bile duct. Transpapillary cytology indicated CD20-positive atypical lymphocytes. MALT lymphoma of the bile duct was diagnosed. CVP with rituximab therapy was performed. After treatment, computed tomography, gastrointestinal endoscopy, endoscopic retrograde cholangiopancreatography, intraductal ultrasonography, and transpapillary cytology revealed that the tumor and the biliary wall thickening had disappeared. It is difficult to diagnose MALT lymphoma of the bile duct. We report a case in which intraductal ultrasound and transpapillary cytology were useful for establishing a diagnosis and evaluating the therapy for MALT lymphoma of the bile duct.

Effect of heat-treatment on the pH sensitivity of stainless-steel electrodes as pH sensors.

Effect of heat-treatment on the pH sensitivity of uncoated stainless-steel electrodes was investigated to comprehend the pH sensitivity of metal-oxide coated stainless-steel electrodes as novel pH sensors. The pH sensitivity of stainless-steel electrodes as-received and heat-treated at 500 °C, 600 °C and 700 °C for 24 h were 91 %, 94 %, 102 % and 91 %, respectively. The pH sensitivity tended to increase with increasing heat-treatment time at a given temperature. Thus, the most suitable heat-treatment condition for the stainless-steel electrodes was 600 °C for 24 h. The austenite phase (fcc) was the main phase on the surface of the heat-treated stainless-steel electrodes. Unexpectedly, the change in the martensite phase (bcc) as the second phase with heat-treatment temperature was similar to the pH sensitivity, with the martensite phase affecting the pH sensitivity. Therefore, it appeared that the pH sensitivity of the metal-oxide coated stainless-steel electrodes was affected by the underlying stainless-steel as well as the outer metal-oxide film coating. A prototype stainless-steel tube electrode was used as a working electrode for demonstrating the depth profiling of pH. The stainless-steel tube electrode showed good performance for measuring pH depth profiles compared to commercially available glass electrodes.

Light-chain plasma cell myeloma caused by 14q32/IGH translocation and loss of the other allele.

Light-chain plasma cell myeloma (LC-PCM) is a PCM subtype in which only immunoglobulin light-chain is secreted. However, the absence of immunoglobulin heavy-chain (IGH) production in this condition has not been fully elucidated. To address this issue, we retrospectively analyzed patients at our center with LC-PCM and found a group who had only split signals of IGH gene derived from 14q32/IGH translocations by fluorescence in situ hybridization (FISH). Six patients were identified with only split signals of the IGH gene derived from 14q32/IGH translocations. Five of these patients were newly diagnosed, while one had IgG-λ PCM at presentation, which transformed to λ LC-PCM after treatment. The translocation partners were identified in four patients: two cases of (11;14)(q13;q32) and two cases of (4;14)(p16;q32). The development of LC-PCM appears to be explained by the application of allelic exclusion in these patients, such that 14q32/IGH translocation in one allele contributes to the pathogenesis of PCM and the subsequent loss of the other allele is responsible for the loss of IGH production. These findings suggest that a FISH pattern of IGH with "split and loss" may constitute a unique subgroup of LC-PCM.

Correction to: Cell dynamics during differentiation therapy with all-trans retinoic acid in acute promyelocytic leukemia.

In the original publication of the article, Table 2 was published incorrectly. The column names were swapped under the column heading "Prom (%)". The correct column names are PB and BM.

Cell dynamics during differentiation therapy with all-trans retinoic acid in acute promyelocytic leukemia.

The introduction of all-trans retinoic acid (ATRA) has made acute promyelocytic leukemia (APL) a curable disease; however, early death prior to the completion of treatment remains a problem. In quantitative evaluation of response to ATRA treatment, lymphocytes must be excluded as they do not originally have t(15;17). We categorized peripheral blood leukocytes by nuclear morphology into polymorphonuclear cells (PMNs) comprising segmented granulocytes, and non-polymorphonuclear cells (NPMs) which includes lymphocytes, monocytes, band cells, and immature myeloid cells. We consecutively evaluated the ratio of t(15;17)-positive cells using fluorescence in situ hybridization in eight newly diagnosed patients with APL. We confirmed the differentiation of APL cells until cytogenetic complete remission; the association of a decrease of t(15;17)-positive NPMs and an increase of t(15;17)-positive PMNs was followed by a decrease of t(15;17)-positive PMNs. The kinetic pattern of t(15;17)-positive NPMs and PMNs was consistent in most patients, irrespective of leukocyte counts at diagnosis, additional chromosomal changes, and ATRA with or without chemotherapies. Kinetic analysis enables us to evaluate treatment response and the recovery of normal hematopoiesis in individuals.

[MALT lymphoma with t (X;14) (p11.2;q32) developing during the course of cutaneous leukocytoclastic angitis].

A 73-year-old man with left parotid gland swelling over 2 months was referred to our hospital in March 201X. Purpura on the lower legs had been recurrent for >20 years. Biopsy of the parotid gland demonstrated diffuse infiltration of abnormal lymphocytes that were negative for CD10 and positive for CD19, CD20, and κ-chain. The Ki-67 positivity was <10%; lymphoepithelial lesions were observed. The patient was diagnosed with extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). Chromosome analysis revealed t (X;14) (p11.2;q32), and fluorescence in situ hybridization (FISH) of metaphase spreads showed three signals of the immunoglobulin heavy chain (IGH) gene on the derivative chromosomes X and 14, besides the normal chromosome 14. CT findings of parotid glands were suggestive of Sjogren syndrome, and biopsy of the purpura on the leg demonstrated leukocytoclastic vasculitis. In the literature, only seven patients with lymphoma and t (X;14) translocation have been reported. Of these, five patients had MALT lymphoma, one had nodal marginal zone lymphoma, and one had diffuse large B-cell lymphoma. In all patients, lymphoma evolved from previous autoimmune diseases. It is suggested that MALT lymphoma with the t (X;14) translocation forms a new entity of lymphoma.

Expression of activating natural killer-cell receptors is a hallmark of the innate-like T-cell neoplasm in peripheral T-cell lymphomas.

Peripheral T- or natural killer (NK)-cell lymphomas are rare and difficult-to-recognize diseases. It remains arduous to distinguish between NK cell- and cytotoxic T-lymphocyte-derived lymphomas through routine histological evaluation. To clarify the cells of origin, we focused on NK-cell receptors and examined the expression using immunohistochemistry in 22 cases with T- and NK-cell neoplasms comprising angioimmunoblastic T-cell lymphoma, anaplastic lymphoma kinase (ALK)-positive and -negative anaplastic large-cell lymphomas, extranodal NK/T-cell lymphoma, nasal type, monomorphic epitheliotropic intestinal T-cell lymphoma, aggressive NK-cell leukemia, and other peripheral T-cell lymphomas. Inhibitory receptor leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1) was detected in 14 (64%) cases, whereas activating receptors DNAM1, NKp46, and NKG2D were expressed in 7 (32%), 9 (41%), and 5 (23%) cases, respectively. Although LILRB1 was detected regardless of the disease entity, the activating NK-cell receptors were expressed predominantly in TIA-1-positive neoplasms (DNAM1, 49%; NKp46, 69%; and NKG2D, 38%). In addition, NKp46 and NKG2D were detected only in NK-cell neoplasms and cytotoxic T-lymphocyte-derived lymphomas including monomorphic epitheliotropic intestinal T-cell lymphoma. One Epstein-Barr virus-harboring cytotoxic T-lymphocyte-derived lymphoma mimicking extranodal NK/T-cell lymphoma, nasal type lacked these NK-cell receptors, indicating different cell origin from NK and innate-like T cells. Furthermore, NKG2D expression showed a negative impact on survival among the 22 examined cases, which mainly received the standard chemotherapy regimen (log-rank test, P = .024). We propose that the presence of activating NK-cell receptors may provide new insights into understanding peripheral T-cell lymphomas and characterizing them as innate-like T-cell neoplasm.

De novo acute lymphoblastic leukemia-like disease of high grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements: a case report and literature review.

BACKGROUND: B-cell lymphomas harboring the 8q24/MYC plus 18q21/BCL2 translocations are now referred to as high grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (HGBL-MBR). Although HGBL-MBR is frequently found in cases with diffuse large B-cell lymphoma or Burkitt lymphoma-like B-cell lymphoma, acute lymphoblastic leukemia (ALL)-like disease of HGBL-MBR (AL-HGBL-MBR) has been reported incidentally. CASE PRESENTATION: A 69-year-old Japanese woman developed remittent fever and increasing systemic bone pain. The bone marrow examination revealed that more than 90% of nuclear cells were blastoid cells, which were positive for CD10, CD19, CD20, and surface IgMκ and negative for terminal deoxynucleotidyl transferase (TdT). Cytogenetic studies confirmed that the patient had de novo AL-HGBL-MBR with the extra copies of MYC and loss of chromosome 17p. She showed resistance to chemoimmunotherapy and died seven months after the diagnosis. The literature review identified further 47 de novo AL-HGBL-MBR cases within the last 32 years. The median age was 61 years (range, 27 - 86); the male/female ratio was 2.0. Thirty-eight cases (79%) presented a clinical picture of ALL at diagnosis; 14 (36%) of 39 available cases showed central nervous system involvement. Loss of 17p and translocations at 2p12-13, 3q27, 9p13 were frequently observed as additional cytogenetic abnormalities. Although the median survival of 46 available cases was only five months (range, 0.1-18), rituximab use significantly improved the survival of AL-HGBL-MBR (log-rank test, P = 0.0294). CONCLUSION: Our patient and most reported de novo AL-HGBL-MBR cases showed resistance to conventional chemoimmunotherapy and disastrous consequences. AL-HGBL-MBL is a rare, but should be considered a distinct clinical condition in HGBL-MBR. Other therapeutic strategies, such as using inhibitors of MYC and BCL2, are needed to overcome the chemoresistance of AL-HGBL-MBR.

Acute myeloid leukemia with t (3;8) (q26.2;q24), a simple variant of 3q26.2/EVI1 translocation.

A 70-year-old man with pancytopenia was referred to our hospital. His bone marrow comprised 75.4% leukemic blast cells and increased micromegakaryocytes. The leukemic cells were positive for myeloperoxidase and expressed CD2, CD13, CD33, CD34, CD56, CD117, HLA-DR, and MYC. Chromosomal analysis revealed 45,XY,t (3;8) (q26.2;q24),-7[6]/46,XY[14]. Fluorescence in situ hybridization revealed the rearrangement of the ecotropic viral integration site 1 (EVI1) gene. Thus, the patient was diagnosed as having acute myeloid leukemia (AML) with maturation, according to the WHO classification; he achieved complete cytogenetic remission after two courses of combination chemotherapy using anthracyclines and cytarabine. The t (3;8) translocation is a rare simple variant of the 3q26.2/EVI1 translocation, which is an adverse prognostic factor of AML. Clarifying the clinical features of leukemia in patients with simple variant translocations facilitates the development of therapies.

Acute myeloid leukemia with t(3;21)(q13;q22), a novel simple variant of the 21q22/RUNX1 translocation.

A 69-year-old man diagnosed with leukocytosis was referred to our hospital in July 201X. The patient was diagnosed as having a myelodysplastic/myeloproliferative neoplasm. However, he presented with leukemia 2 months later. Chromosomal analysis of a bone marrow sample documented that this patient had a normal karyotype. The patient was successfully treated with idarubicin and cytarabine, and he underwent three courses of consolidation therapy. However, he suffered a relapse in May of the following year. A cytogenetic analysis revealed the presence of a t (3;21) (q13;q22) translocation, and fluorescence in situ hybridization of metaphase spreads detected three signals corresponding to the runt related transcription factor 1 (RUNX1) on the derivative chromosomes 3 and 21, besides the normal chromosome 21. Chromosomal translocations in leukemia often involve genes encoding transcription factors, and the RUNX1 is a common target for such translocations. To the best of our knowledge, this is a novel variant of the RUNX1 translocation. Identifying genes associated with translocations in leukemia contributes to novel insights into the mechanisms of disease progression and chemotherapy resistance and also facilitates the development of molecularly targeted therapies.

PAX5-positive plasma cell myeloma with t(9;14;11)(p13;q32;q13), a novel complex variant translocation of t(11;14)(q13;q32) and t(9;14)(p13;q32).

We describe herein the case of a 64-year-old man with a diagnosis of plasma cell myeloma (PCM). A chromosome analysis based on G-banding and spectral karyotyping revealed the following complex karyotype: 46,XY,del(3)(p?), t(4;15)(q31;q24),t(9;14;11)(p13;q32;q13),add(15)(q24),add(18)(q21). Fluorescence in situ hybridization (FISH) detected one signal each for the immunoglobulin heavy chain (IGH) and cyclin D1 (CCND1) genes, and three fusion signals of IGH and CCND1. FISH analysis of metaphase spreads revealed fusion signals on the derivative chromosomes 9, 11, and 14. Immunohistochemical analysis identified abnormal expression of CCND1 and PAX5. PAX5-positive PCM is rare because the down-regulation of PAX5 is essential for the terminal differentiation of B cells into plasma cells. To the best of our knowledge, this is the first reported case of a novel complex variant translocation of t(11;14)(q13;q32) and t(9;14)(p13;q32).

Drastic Dependence of the pH Sensitivity of Fe2O3-Bi2O3-B2O3 Hydrophobic Glasses with Composition.

Fe2O3-Bi2O3-B2O3 (FeBiB) glasses were developed as novel pH responsive hydrophobic glasses. The influence of the glass composition on the pH sensitivity of FeBiB glasses was investigated. The pH sensitivity drastically decreased with decreasing B2O3 content. A moderate amount of Fe2O3 and a small amount of B2O3 respectively produces bulk electronic conduction and a pH response on glass surfaces. Because the remaining components of the glass can be selected freely, this discovery could prove very useful in developing novel pH glass electrodes that are self-cleaning and resist fouling.

Cytogenetic Study and Analysis of Protein Expression in Plasma Cell Myeloma with t(11;14)(q13;q32): Absence of BCL6 and SOX11, and Infrequent Expression of CD20 and PAX5.

The t(11;14)(q13;q32) translocation is the most common chromosomal translocation in plasma cell myeloma (PCM), but the cytogenetic and immunophenotypic features of PCM with t(11;14)(q13;q32) remain to be fully elucidated. To address the issue, we retrospectively analyzed 21 newly diagnosed PCM patients with the t(11;14)(q13;q32) translocation in our institute. CD20 is a B-cell-specific transmembrane protein that is the topic of much focus as a potential target in immunotherapy. We observed a low incidence of CD20 expression (2 of 21 patients, 11%), although the expression of CD20 was previously reported to be associated with t(11;14)(q13;q32). PAX5 is an essential transcriptional factor involved in B-cell development and commitment, and is down-regulated upon plasma cell differentiation. We observed one patient (6%) with expression of PAX5. The expression of CD19, CD56, and CD138 was detected in one (0.7%), nine (60%), and 13 patients (87%), respectively. Cyclin D1, CD38, and BCL2 were detected in all patients; on the other hand, neither BCL6 nor SOX11 was detected in any of the evaluated patients. Abnormalities of chromosome 13 were detected in six patients (38%), but deletion of TP53 was not observed in any of the evaluated patients. Our results suggest the absence of BCL6 and SOX11 expression, and infrequent expression of CD20, PAX5, and CD56 in PCM with t(11;14)(q13;q32), in contrast to the findings of earlier reports.

Pharmacokinetics of cyclosporine a conversion from twice-daily infusion to oral administration in allogeneic hematopoietic stem cell transplantation.

Twice-daily administration of cyclosporine A (CyA) has often been used for prophylaxis of acute graft versus host disease in allogeneic hematopoietic stem cell transplantation (allo-HSCT). But there have not been any reports that calculated the conversion ratio of the switch from twice-daily intravenous infusion to oral administration of CyA in adult patients. To establish the conversion ratio and the best strategy of twice-daily administration of CyA, the authors investigated the serial changes in the blood CyA concentration during the switch from twice-daily intravenous infusion to oral administration while maintaining high-peak concentration (over 1000 ng/mL) and calculated the bioavailability of Neoral, a micro emulsion cyclosporine, in 11 patients. All the patients underwent allo-HSCT with graft versus host disease prophylaxis consisting of CyA at a high-peak concentration of twice-daily infusion with short-term methotrexate and oral administration. Neoral was started at an oral dose, 2 times daily, at twice the latest dose of intravenous dose according to the bioavailability of healthy volunteers. Micafungin, a mild inhibitor of CYP3A4, was administered for prophylaxis against fungal infection. The total area under the concentration-time curve during oral administration (AUCpo) was nearly the same as AUC during intravenous infusion (AUCiv) (mean ± SD, 7206 ± 1557 ng·h·mL and 7783 ± 897.7 ng·h·mL, respectively). The bioavailability of Neoral, defined as F = AUCpo × DOSEiv/AUCiv × DOSEpo was 0.58 ± 0.15 (mean ± SD, range: 0.41-0.94). When patients were switched from twice-daily infusion to oral administration, the dose conversion ratio of 1:2 seemed to be appropriate. At that time, the target trough level of Neoral was nearly the same as that of the infusion.

Importance of appropriate pharmaceutical management in pregnant women with ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) often occurs in women of childbearing age. Compared to Western countries, however, few studies have investigated the impact of UC on the progress of pregnancy in Asian populations. METHODS: We retrospectively examined 91 pregnancies in 64 patients with UC experienced at our hospital and related institutions from 1991 to 2011, focusing on the relationship between the progression of UC during pregnancy, progress of the pregnancy itself, and the treatment of UC. RESULTS: In 80 of 91 pregnancies the patient had already been diagnosed with UC at the time she became pregnant, of whom 31 (38.8%) experienced exacerbation during pregnancy. Regarding severity, moderate or severe active-stage disease during pregnancy was seen in 13.7% of those who had been in remission at the onset of pregnancy versus 58.6% of those who had been in the active stage at onset (OR 8.9: 95%CI 3.0~26.4; P<0.01). The incidence of miscarriage or abortion was 9.8% in pregnancies in which UC was in remission at onset versus 31% in those in which it was in the active stage at onset (OR 4.1: 95%CI 1.2~13.9; P=0.02). Among patients, 62.5% were receiving pharmaceutical treatment at onset of pregnancy. Exacerbation during pregnancy occurred in 26.5% of the group who continued to receive the same treatment during pregnancy versus 56.3% of those with a dose decrease or discontinuation after onset (OR 3.6: 95%CI 1.0~12.4; P=0.04). CONCLUSIONS: UC patients wishing to conceive should do so when in remission and continue appropriate pharmaceutical treatment during pregnancy.

Role of serum high mobility group box 1 in hematological malignancies complicated with systemic inflammatory response syndrome and effect of recombinant thrombomodulin.

High mobility group box 1 (HMGB1) mediates inflammation. We investigated the role of serum HMGB1 in 54 patients with hematological malignancies with and without systemic inflammatory response syndrome (SIRS). There was no difference between groups 1 (complete remission of hematological disease: n = 13) and 2 (no remission: n = 16) in serum HMGB1 levels. However, those of group 3 (complicated by SIRS: n = 25) were significantly higher (vs. group 1: p < 0.001 and vs. group 2: p = 0.008, respectively). Seventeen patients in group 3 also developed disseminated intravascular coagulation and received recombinant human thrombomodulin (rhTM). Thirteen of those with SIRS improved, and serum HMGB1 levels significantly decreased (p = 0.047). Seven patients in group 3 who died within 28 days of SIRS onset had significantly higher serum HMGB1 levels than the survivors (p = 0.016). The anti-HMGB1 properties of rhTM might be useful therapy if serum HMGB1 is associated with the development of SIRS in the presence of hematological malignancies.

Drug interactions between micafungin at high doses and cyclosporine A in febrile neutropenia patients after allogeneic hematopoietic stem cell transplantation.

OBJECTIVES: The aim of this study was to assess the drug interaction between high doses of micafungin and cyclosporine A (CyA) in allo-HSCT patients. METHODS: We assigned 15 patients to Groups 1, 2, or 3. We investigated the serial changes in the blood concentration/dose (C/dose) of intravenous CyA during micafungin coadministration in 5 patients during the switch from the prophylactic dose (150 mg/body) to the therapeutic dose (300 mg/body) of micafungin (Group 1), and compared each of the 5 patients in Group 1 with those who continued to receive the prophylactic doses of 150 mg or 50 mg/body of micafungin (Groups 2 and 3). We collected blood samples from patients in Group 1 receiving CyA at 0 h (C0) and (C3) 3 h on the 7th day after allo-HSCT, and on the 3rd and 10th days after escalation of the dose of micafungin to 300 mg. RESULTS: In Group 1, no significant difference was observed between C0/dose (2.11 ± 0.14) and C3/dose ratios of CyA (11.1 ± 5.34, p > 0.05) under 150 mg; the C0/dose and C3/dose ratios of CyA were 2.40 ± 0.60 and 10.8 ± 4.72 on the 3rd day and 2.23 ± 0.41 and 11.8 ± 3.06 on the 10th day, respectively, after dose escalation of micafungin to 300 mg. No significant differences were observed in those ratios between Groups 1 and 2 and between Groups 1 and 3. CONCLUSION: Thus, high dose of micafungin seems to be safe and does not significantly interact with CyA in allo-HSCT.