Leukemic stem cells (LSCs) are root of clonal growth in acute myeloid leukemia (AML) and responsible for the propagation of leukemic blasts (LBs). LSCs are considered as CD34 + CD38− population among ...LBs and often express as CD123, CD44, or CD184, which are rarely expressed on normal hematopoietic stem cells and could be the potential therapeutic targets. Using multi-color flow cytometry, we analyzed the proportions of CD34 + CD38− LSCs and expression of CD123, CD44, and CD184 on LSCs in 63 patients with AML. The median proportion of LSCs was 1.3 % (0.0–33.1 %) at the time of diagnosis. Of all patients, 74.6 % of them had CD123-positive LSCs, all patients had CD44-positive LSCs, and 85.7 % had CD184-positive LSCs, respectively. The proportions of LSCs were significantly lower in the complete remission (CR) group compared with non-CR group (
P
= 0.006). The lower proportions of LSCs in CR group indicated that measurement of the proportion of LSCs might be helpful to predict the prognosis of AML.
The plasma screening and quantum effects on ion--ion collisions are investigated in a nonideal Al and Cu dense metal plasma. Eikonal analysis and the effective pseudopotential model of the ...quantum--mechanical and plasma screening effects are used to obtain the eikonal phase shift and eikonal cross section for the ion--ion collision as functions of the impact parameter, collision energy, de Broglie wavelength, and Debye length in nonideal metal plasmas. The result shows that the plasma screening effect is more important than the quantum--mechanical effect in ion collisions in nonideal metal plasmas. The result shows that the eikonal phase shift decreases with an increase in the quantum--mechanical effect. Note that the Al--Cu ion collision cross section is found to be greater than the Al--Al and Cu--Cu ion collision cross sections in a dense metal plasma.
The purpose of this study was to investigate the correlation of mutations of the fms-like tyrosine kinase (
FLT3
) and nucleophosmin (
NPM1
) genes with the cup-like nuclear morphology of blasts in ...patients with acute myeloid leukemia (AML). We retrospectively reviewed peripheral blood (PB) and bone marrow (BM) slides of 208 patients prepared at the time of diagnosis of AML based on the results of testing for mutations of both
NPM1
exon 12 and
FLT3
. We investigated the association between this phenotype and hematologic findings, disease markers, and mutations in
NPM1
exon 12,
FLT3
-internal tandem duplication (ITD), and tyrosine kinase domain (TKD) genes. Cup-like nuclei were found in 44 patients (21.2 %) diagnosed with AML. This morphology was associated with high blast counts in the PB and BM; AML type, especially AML M1 (FAB classification); low CD34 expression; and mutation of
FLT3
-ITD, -TKD,
NPM1
regardless of other mutations (
p
< 0.05 for all). However,
FLT3
-ITD or TKD mutation alone (nine cases,
p
= 0.228) was not associated, and
NPM1
mutation alone (14 cases,
p
= 0.036) was weakly associated with cup-like nuclei. Mutation of both
NPM1
and
FLT3
-ITD or TKD (17 cases,
p
< 0.001) was strongly correlated with the cup-like nuclear morphology. AML with cup-like nuclei is strongly associated with co-occurring mutations of both
NPM1
and
FLT3
-ITD or TKD. Therefore, testing for both mutations is recommended for patients with the cup-like nuclear morphology.
Introduction
Genetic background influences neurotransmitter expression and function of the hippocampus. Genetic background influences the phenotype of the hippocampus, but expression of neuroglia in ...hippocampus has not been well established dependent on various mouse strains.
Objectives
In this study, we investigated the effects of genetic background on cell population of astrocytes and microglia in eight widely used inbred strains (C57BL/6J, A/J, BALB/c, C3H/HeJ, FVB, 129/SvJ, DBA/1, and DBA/2) and one outbred strain (ICR).
Methods
In all mouse strains, glial fibrillary acidic protein (GFAP)‐immunoreactive astrocytes and ionized calcium‐binding adaptor molecule 1 (Iba‐1)‐immunoreactive microglia were found in almost all layers of hippocampal CA1‐4 regions and the dentate gyrus.
Results
We observed significant differences in the number of astrocytes and microglia. In the CA1 and CA3 regions, the number of GFAP‐immunoreactive astrocytes was highest in the C3H/HeJ strain, and lowest in the 129/SvJ and FVB strains. In the polymorphic layer of the dentate gyrus, the number was highest in the DBA/1 strain and lowest in the 129/SvJ strain. Among the nine mouse strains, the number of Iba‐1‐immunoreactive microglia was highest in the CA1 and CA3 regions in the ICR and in the dentate gyrus of the C57BL/6 strain. The CA1 region of the FVB strain and the CA3 region and dentate gyrus of DBA/2 had the lowest number of Iba‐1‐immunoreactive microglia.
Conclusion
These results suggest that the numbers of astrocytes and microglia differ depending on the mouse strain and these differences may be related to strain‐dependent function of astrocytes.
In this study, we investigated the effects of genetic background on cell population of astrocytes and microglia in eight widely used inbred strains (C57BL/6J, A/J, BALB/c, C3H/HeJ, FVB, 129/SvJ, DBA/1, and DBA/2) and one outbred strain (ICR). These results suggest that the numbers of astrocytes and microglia differ depending on the mouse strain, and these differences may be related to strain‐specific metabolic processes in astrocytes.
In this experiment, we verified the effects of
Dendropanax morbifera
Léveille stem extract (DMS) on hypothyroidism-induced oxidative stress in the hippocampus of rats. Hypothyroidism was induced in ...rats by treating them with 0.03% 2-mercapto-1-methyl-imidazole dissolved in drinking water for 5 weeks. DMS (100 mg/kg) was also orally administered to the rats during the same period and the animals were sacrificed at 12 weeks of age. DMS administration tended to ameliorate these hypothyroidism-induced changes in serum triiodothyronine (T
3
), thyroxine (T
4
), and thyroid-stimulating hormone levels. DMS administration significantly reduced the hypothyroidism-induced increases in reactive oxygen species production as well as in lipid peroxidation in the hippocampus. In addition, DMS administration increased hippocampal Cu, Zn-superoxide dismutase (SOD1), catalase (CAT), and glutathione peroxidase (GPx) levels. These results suggest that DMS potentially ameliorates hypothyroidism-induced neuroendocrine phenotypes and oxidative stress in the hippocampus via the induction of antioxidant enzymes.
Health-related quality of life (HRQOL) is an important outcome indicator for chronic disease, and particularly in the absence of biological markers for illness, such as with irritable bowel syndrome ...(IBS). The aims of this study were to develop and evaluate a new IBS-specific HRQOL instrument (IBS-HR-QOL).
This methodological study comprised three steps: conceptualization of the IBS-HR-QOL, item extraction and establishment of content validity, and psychometric evaluation of the instrument with 267 IBS patients recruited from four university hospitals.
The content validity of the developed IBS-HR-QOL was assessed by 11 experts. Exploratory and confirmatory factor analyses yielded four factors. The criterion and convergent validities of the IBS-HR-QOL were demonstrated using the Short Form-36 and the Hospital Anxiety and Depression Scale, respectively. Known-groups validity was demonstrated using a symptom-severity scale. The internal consistency reliability and test-retest reliability were satisfactory, with a Cronbach's alpha and intraclass correlation coefficient of 0.93 and 0.88, respectively.
The IBS-HR-QOL comprises a total of 16 items. The IBS-HR-QOL demonstrated good psychometric properties. This instrument is easily comprehensible and short, rendering it feasible for use in clinical practice and research.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The Lorentzian renormalization plasma shielding effects on the elastic electron–atom collision are investigated in generalized Lorentzian semiclassical plasmas. The eikonal analysis and the effective ...interaction potential are employed to obtain the eikonal scattering phase shift, differential eikonal collision cross section, and total eikonal collision cross section as functions of the collision energy, impact parameter, nonthermal renormalization parameter, and spectral index of the Lorentzian plasma. It is found that the influence of Lorentzian renormalization shielding suppresses the eikonal scattering phase shift and, however, enhances the eikonal collision cross section in Lorentzian semiclassical plasmas. Additionally, the energy dependence on the total collision cross section in nonthermal plasmas is found to be more significant than that in thermal plasmas.
Introduction
Precommunicating (A1) segment aneurysms of the anterior cerebral artery are rare and often pose technical challenges for coil embolization due to their distinctive configurations. ...Clinical and radiologic outcomes of treating such aneurysms through endovascular coil embolization are presented herein.
Methods
Data accruing prospectively from May 2002 to August 2013 yielded 48 patients harboring 50 A1 segment aneurysms, each classified as proximal, middle, or distal by location. Clinical outcome of the patients and morphological outcome of the aneurysms were assessed, with emphasis on technical aspects of treatment.
Results
The aneurysms studied occupied either proximal (
n
= 39), middle (
n
= 6), or distal (
n
= 5). Proximal aneurysms were largely directed posteriorly (80 %), and most (97 %) were devoid of branches. Middle and distal aneurysms were associated with the medial lenticulostriate artery, cortical branches, or fenestrations. The preshaped “S” and steam-shaped “S” microcatheters facilitated aneurysm selection in 60 % of lesions. Single-microcatheter technique was most commonly applied for coil embolization (62 %), followed by balloon protection (16 %). Successful aneurysmal occlusion could be achieved in 76 % of the patients, with no procedure-related morbidity and mortality. At final follow-up (mean interval, 29.9 months), stable aneurysmal occlusion was sustained in 93 % of the patients (40/43).
Conclusion
A1 segment aneurysms are amenable to safe and efficacious endovascular coil embolization by adjusting procedural strategy to accommodate distinctive anatomic configurations.
In this study, we investigated the effects of chronic aluminum (Al) exposure for 10 weeks on cell proliferation and neuroblast differentiation in the hippocampus of type 2 diabetic rats. Six-week-old ...Zucker diabetic fatty (ZDF) and Zucker lean control (ZLC) rats were selected and randomly divided into Al- and non-Al-groups. Al was administered via drinking water for 10 weeks, after which the animals were sacrificed at 16 weeks of age. ZDF rats in both Al- and non-Al-groups showed increases in body weight and blood glucose levels compared to ZLC rats. Al exposure did not significantly affect body weight, blood glucose levels or pancreatic β-cells and morphology of the pancreas in either ZLC or ZDF rats. However, exposure to Al reduced cell proliferation and neuroblast differentiation in both ZLC and ZDF rats. Exposure to Al resulted in poor development of the dendritic processes of neuroblasts in both ZLC and ZDF rats. Furthermore, onset and continuation of diabetes reduced cell proliferation and neuroblast differentiation, and Al exposure amplified reduction of these parameters. These results suggest that Al exposure via drinking water aggravates the impairment in hippocampal neurogenesis that is typically observed in type 2 diabetic animals.
▪
Introduction: We conducted a randomized trial comparing two different doses of daunorubicin as induction chemotherapy in young adults with acute myeloid leukemia (AML) and showed intensification of ...induction therapy using a high daily dose of daunorubicin (90 mg/m2/d x 3d) improved both complete remission (CR) rate and survival duration compared to standard daunorubicin dose (45 mg/m2/d x 3d) (Lee JH et al. Blood 2011;118:3832). As it is necessary to compare the effects of high-dose daunorubicin with that of other agents, especially idarubicin, we performed another randomized trial comparing two induction regimens in young adults with AML: idarubicin vs. high-dose daunorubicin (ClinicalTrials.gov #NCT01145846). Here, we present final results of the study.
Methods: Between May 2010 and March 2014, a total of 316 patients (65 years or younger) with newly diagnosed AML except acute promyelocytic leukemia were registered in this study. Seventeen patients were removed from the study (change of diagnosis in 11, patient's refusal to be randomized in 3 and other in 3) and the remaining 299 patients were analyzed. After random assignments, 149 patients received idarubicin (AI, 12 mg/m2/d x 3d) and 150 patients received high-dose daunorubicin (AD, 90 mg/m2/d x 3d) in addition to cytarabine (200 mg/m2/d x 7d) for induction of CR. Patients with persistent leukemia received the second attempt of induction chemotherapy, consisting of idarubicin (AI, 12 mg/m2/d x 2d) or daunorubicin (AD, 45 mg/m2/d x 2d) plus cytarabine (5d). Patients who attained CR received 4 cycles of high-dose cytarabine (3 g/m2 x 6 doses) in patients with good- or intermediate-risk cytogenetics and 4 cycles of cytarabine (1 g/m2 x 6d) plus etoposide (150 mg/m2 x 3d) in those with high-risk cytogenetics. Hematopoietic cell transplantation (HCT) was performed according to attending physician's discretion after one or two cycles of consolidation chemotherapy in most transplant cases.
Results: CR was induced in 232 (77.6%) of 299 patients. Reasons for induction failure were resistant disease in 50, hypoplastic death in 5, and indeterminate cause in 12. As postremission therapy, 3 patients received no further treatment, 71 received consolidation chemotherapy without HCT, 137 underwent allogeneic HCT, and 21 underwent autologous HCT. The CR rates were not significantly different between two arms: 80.5% (120 of 149, AI) vs. 74.7% (112 of 150, AD) (P=0.224). With a median follow-up of 1046 days, overall survival probabilities at 4 years were 51.1% in AI vs. 54.7% in AD (P=0.756). The probabilities at 4 years for relapse-free survival were 63.5% in AI vs. 74.2% in AD (P=0.181) and those for event-free survival were 44.8% in AI vs. 50.7% in AD (P=0.738). Toxicity profiles were similar between two arms. Interestingly, overall and event-free survivals of 44 patients with FLT-ITD mutants (27 in AI and 17 in AD) were significantly different according to the induction regimens (AI vs AD; overall survival, 30.8% vs. 61.9%, P=0.030; event-free survival, 31.4% vs. 61.9%, P=0.025).
Conclusions: The results of this phase 3 trial, which compared idarubicin (12 mg/m2/d x 3d) with high-dose daunorubicin (90 mg/m2/d x 3d), did not show significant differences between two arms in the outcomes of patients in terms of CR rates and overall, relapse-free or event-free survivals. In subset analysis, high-dose daunorubicin seems to be more effective than idarubicin in patients with FLT-ITD mutants.
Kim:Celgene: Research Funding; Alexion Pharmaceuticals: Research Funding; Il-Yang: Research Funding; Novartis: Research Funding.
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