Effects of Kurozu concentrated liquid on adipocyte size in rats

<p>Abstract</p> <p>Background</p> <p>Kurozu concentrated liquid (KCL) is used as a health-promoting supplement for the treatment of disorders such as cancer, hyperlipidemia, and hypertension in Japan. We investigated the possible anti-obesity effects of KCL in rats.</p> <p>Methods</p> <p>Male Sprague Dawley rats were fed American Institute of Nutrition 76 formula diet and were orally administrated KCL or acetic acid at a dose of 100 mg/kg body weight or deionized water for 4 weeks. Adipocyte size, DNA content in subcutaneous adipose tissue, lipid levels in the serum and liver, and the rate of fatty acid excretion were determined. Effects of KCL on pancreatic lipase activity and 3T3-L1 preadipocyte differentiation were investigated <it>in vitro</it>.</p> <p>Results</p> <p>In the KCL group, the average adipocyte size in subcutaneous and perirenal adipose tissues was significantly reduced. The KCL-administered rats displayed greater numbers of small adipocytes in the subcutaneous, perirenal and mesenteric adipose tissues than did rats from the other groups. In the KCL group, the DNA content in subcutaneous adipose tissue was significantly increased. The rate of fatty acid excretion was significantly increased in the KCL group. Furthermore, KCL significantly inhibited pancreatic lipase activity <it>in vitro</it>, and also significantly inhibited fat accumulation and mRNA expression of fatty acid binding protein 2 (aP2) and peroxisome proliferator-activated γ (PPARγ) in 3T3-L1 preadipocyte. The levels of serum and liver lipids, the concentration of serum glucose, and the levels of adiponectin were similar among the 3 groups.</p> <p>Conclusion</p> <p>Oral administration of KCL decreases the adipocyte size <it>via </it>inhibition of dietary fat absorption and reductions of PPARγ and aP2 mRNA expression levels in adipocytes.</p

Role of a forward-viewing echoendoscope in fine-needle aspiration

AbstractA prototype forward-viewing echoendoscope has been developed for therapeutic endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). The hard tip of the forward-viewing echoendoscope, which is shorter than that of the convex type echoendoscope, can be maneuvered flexibly. Using the forward-viewing echoendoscope, the gastrointestinal wall can be vertically punctured along the same axis as the scope, and this process is done more easily than with an oblique-viewing echoendoscope. The diagnostic accuracy of EUS-FNA with the forward-viewing echoendoscope is 97.4%, which is not significantly different to that of the oblique-viewing echoendoscope. The forward-viewing echoendoscope may be useful in situations where the location and procedure are difficult with the oblique-viewing scope, The forward-viewing echoendoscope is able to puncture the gastrointestinal wall vertically with minimal effort, therefore allowing therapeutic EUS procedures such as pseudocyst and abscess drainage, biliary drainage, and pancreatic duct drainage to be performed easily. However, a significant difference between the forward-viewing and oblique-viewing echoendoscopes in pseudocyst drainage has been reported recently. In the future, the forward-viewing and oblique-viewing echoendoscopes will probably be selectively used depending on not only lesion site but also the procedure required in individual patients, thereby facilitating various processes including puncture, tissue collection, and diagnosis, as well as therapeutic procedures

Erratum to: Expression of myeloperoxidase and gene mutations in AML patients with normal karyotype: double CEBPA mutations are associated with high percentage of MPO positivity in leukemic blasts

Erratum to: International Journal of Hematology, 94(1), pp.81-89: 2011DOI 10.1007/s12185-011-0883-yThe original version of this article unfortunately contained some errors in Table 2 in the column headed ‘‘Amino acid changes’’. The corrected table is given here

Integrated genetic and clinical prognostic factors for aggressive adult T-cell leukemia/lymphoma

成人T細胞白血病リンパ腫（ATL）におけるゲノム情報と臨床情報を統合したリスクモデルを確立 --ATLの個別化医療を推進--. 京都大学プレスリリース. 2023-04-10.The prognosis of aggressive adult T-cell leukemia/lymphoma (ATL) is poor, and allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is a curative treatment. To identify favorable prognostic patients after intensive chemotherapy, and who therefore might not require upfront allo-HSCT, we aimed to improve risk stratification of aggressive ATL patients aged <70 years. The clinical risk factors and genetic mutations were incorporated into risk modeling for overall survival (OS). We generated the m7-ATLPI, a clinicogenetic risk model for OS, that included the ATL prognostic index (PI) (ATL-PI) risk category, and non-silent mutations in seven genes, namely TP53, IRF4, RHOA, PRKCB, CARD11, CCR7, and GATA3. In the training cohort of 99 patients, the m7-ATLPI identified a low-, intermediate-, and high-risk group with 2-year OS of 100%, 43%, and 19%, respectively (hazard ratio [HR] 5.46, p < 0.0001). The m7-ATLPI achieved superior risk stratification compared to the current ATL-PI (C-index 0.92 vs. 0.85, respectively). In the validation cohort of 84 patients, the m7-ATLPI defined low-, intermediate-, and high-risk groups with a 2-year OS of 81%, 30%, and 0%, respectively (HR 2.33, p = 0.0094), and the model again outperformed the ATL-PI (C-index 0.72 vs. 0.70, respectively). The simplified m7-ATLPI, which is easier to use in clinical practice, achieved superior risk stratification compared to the ATL-PI, as did the original m7-ATLPI; the simplified version was calculated by summing the following: high-risk ATL-PI category (+10), low-risk ATL-PI category (−4), and non-silent mutations in TP53 (+4), IRF4 (+3), RHOA (+1), PRKCB (+1), CARD11 (+0.5), CCR7 (−2), and GATA3 (−3)

Successful cord blood transplantation for mycosis fungoides.

A 26-year-old female diagnosed as mycosis fungoides (MF, clinical stage IV) was treated with single-agent chemotherapy, multi-drug chemotherapy and unrelated bone marrow transplantation with reduced-intensity conditioning (engraftment failure), resulting in failure. Unrelated cord blood transplantation (CBT) as second transplantation following myeloablative conditioning brought complete remission (CR), but relapse of MF occurred 3 months after transplantation. However, discontinuation of immune suppressant led to the regression of MF regions and to second CR that continued for more than 23 months. This is the first report of successful CBT for MF, suggesting the graft-versus-MF effect in a setting of CBT.The original publication is available at www.springerlink.co

Successful treatment of a chronic-phase T-315I-mutated chronic myelogenous leukemia patient with a combination of imatinib and interferon-alfa

The T315I BCR-ABL mutation in chronic myelogenous leukemia (CML) patients is responsible for up to 20% of all clinically observed resistance. This mutation confers resistance not only to imatinib, but also to second-generation BCR-ABL tyrosine kinases, such as nilotinib and dasatinib. A number of strategies have been implemented to overcome this resistance, but allogeneic stem cell transplantation remains the only established therapeutic option for a cure. A 61-year-old male was diagnosed with Philadelphia chromosome-positive chronic-phase CML in 2002. He was initially treated with imatinib and complete cytogenetic response (CCyR) was achieved 12 months later. However, after 18 months, a loss of CCyR was observed and a molecular study at 24 months revealed a T315I mutation of the BCR-ABL gene. At 30 months, imatinib/interferon-alfa (IFNα) combination therapy was initiated in an effort to overcome the resistance. Thirty months later, he re-achieved CCyR, and the T315I BCR-ABL mutation disappeared at 51 months. To our knowledge, this is the first case report showing the effectiveness of imatinib/IFNα combination therapy for CML patients bearing the T315I BCR-ABL mutation

Long-term outcome of immunosuppressive therapy for Japanese patients with lower-risk myelodysplastic syndromes

To investigate the long-term usefulness of immunosuppressive therapy (IST) for Japanese patients with lower-risk myelodysplastic syndromes, we retrospectively analyzed 29 MDS patients who were treated with cyclosporine A alone or with anti-thymocyte globulin at a single institute in Japan. A total of 58.6 % of patients showed hematological response to IST. Overall survival of all patients was 74.5 % at 5 years and 48.3 % at 10 years. The major adverse event was the elevation of creatinine level (grade 1 and 2). Eleven patients were still on IST at the time of analysis with, at least, some clinical benefits. Pneumonia was the most frequent cause of death (eight of 12 deaths), followed by bleeding (three of 12); most of the patients who died were non-responders. The presence of paroxysmal nocturnal hemoglobinuria-type cells was significantly associated with both response to IST and long-term survival by univariate analysis. The 10-year overall survival of responders (72.2 %) was significantly superior to that of non-responders (15.6 %, P < 0.0001). These results suggest that IST using cyclosporine A provides long-term benefit for Japanese patients with lower-risk MDS

Relationship between monoclonal gammopathy of undetermined significance and radiation exposure in Nagasaki atomic bomb survivors.

Radiation exposure is a possible predisposing factor for monoclonal gammopathy of undetermined significance (MGUS), but the association has been uncertain. We investigated the relationship between radiation exposure and MGUS prevalence by using data from the M-protein screening for Nagasaki atomic bomb survivors between 1988 and 2004. Radiation exposure was assessed by exposure distance from the hypocenter and exposure radiation dose. We computed prevalence ratios (PRs) and the 95% confidence intervals (CIs) adjusting for exposure age and sex. A total of 1082 cases of MGUS were identified from 52 525 participants. MGUS prevalence was significantly higher in people exposed at distance within 1.5 km than beyond 3.0 km (PR, 1.4; 95% CI, 1.1-1.9) among those exposed at age 20 years or younger, but it was not found among those exposed at age 20 years or older. MGUS prevalence was also significantly higher in people exposed to more than 0.1 Gy than those exposed to less than 0.01 Gy (PR, 1.7; 95% CI, 1.0-2.8) among those exposed at age 20 years or younger. Thus, people exposed at younger age exhibited a significantly high risk of MGUS when exposed to a high radiation dose. There was no clear association between radiation exposure and the malignant progression of MGUS. Further detailed analysis is needed

Expression of myeloperoxidase and gene mutations in AML patients with normal karyotype: double CEBPA mutations are associated with high percentage of MPO positivity in leukemic blasts.

The percentage of myeloperoxidase (MPO)-positive blast cells is a simple and highly significant prognostic factor in AML patients. It has been reported that the high MPO group (MPO-H), in which >50% of blasts are MPO activity positive, is associated with favorable karyotypes, while the low MPO group (≤50% of blasts are MPO activity positive, MPO-L) is associated with adverse karyotypes. The MPO-H group shows better survival even when restricted to patients belonging to the intermediate chromosomal risk group or those with a normal karyotype. It has recently been shown that genotypes defined by the mutational status of NPM1, FLT3, and CEBPA are associated with treatment outcome in patients with cytogenetically normal AML. In this study, we aimed to evaluate the relationship between MPO positivity and gene mutations found in normal karyotypes. Sixty AML patients with normal karyotypes were included in this study. Blast cell MPO positivity was assessed in bone marrow smears stained for MPO. Associated genetic lesions (the NPM1, FLT3-ITD, and CEBPA mutations) were studied using nucleotide sequencing. Thirty-two patients were in the MPO-L group, and 28 patients in the MPO-H group. FLT3-ITD was found in 11 patients (18.3%), NPM1 mutations were found in 19 patients (31.7%), and CEBPA mutations were found in 11 patients (18.3%). In patients with CEBPA mutations, the carrying two simultaneous mutations (CEBPA (double-mut)) was associated with high MPO expression, while the mutant NPM1 without FLT3-ITD genotype was not associated with MPO activity. Both higher MPO expression and the CEBPA (double-mut) genotype appeared to be associated with improved overall survival after intensive chemotherapy. Further studies are required to determine the importance of blast MPO activity as a prognostic factor, especially in CEBPA wild-type patients with a normal karyotype

Molecular analysis of the BCR-ABL1 kinase domain in chronic-phase chronic myelogenous leukemia treated with tyrosine kinase inhibitors in practice: Study by the Nagasaki CML Study Group

An appropriate trigger for BCR-ABL1 mutation analysis has not yet been established in unselected cohorts of chronic-phase chronic myelogenous leukemia patients. We examined 92 patients after 12 months of tyrosine kinase inhibitor (TKI) treatment in Nagasaki Prefecture, Japan. Univariate analysis revealed that significant factors associated with not attaining a major molecular response (MMR) were the presence of the minor BCR-ABL1 fusion gene, a low daily dose of TKI, and the emergence of BCR-ABL1 kinase domain mutations conferring resistance to imatinib. Factors associated with the loss of sustained MMR were a low daily dose of TKI and the emergence of alternatively spliced BCR-ABL1 mRNA with a 35-nucleotide insertion. Taken together, our results suggest that the search for BCR-ABL1 mutations should be initiated if patients have not achieved MMR following 12 months of TKI treatment