Mutated KIT Tyrosine Kinase as a Novel Molecular Target in Acute Myeloid Leukemia

KIT is a type-III receptor tyrosine kinase that contributes to cell signaling in various cells. Since KIT is activated by overexpression or mutation and plays an important role in the development of some cancers, such as gastrointestinal stromal tumors and mast cell disease, molecular therapies targeting KIT mutations are being developed. In acute myeloid leukemia (AML), genome profiling via next-generation sequencing has shown that several genes that are mutated in patients with AML impact patients’ prognosis. Moreover, it was suggested that precision-medicine-based treatment using genomic data will improve treatment outcomes for AML patients. This paper presents (1) previous studies regarding the role of KIT mutations in AML, (2) the data in AML with KIT mutations from the HM-SCREEN-Japan-01 study, a genome profiling study for patients newly diagnosed with AML who are unsuitable for the standard first-line treatment (unfit) or have relapsed/refractory AML, and (3) new therapies targeting KIT mutations, such as tyrosine kinase inhibitors and heat shock protein 90 inhibitors. In this era when genome profiling via next-generation sequencing is becoming more common, KIT mutations are attractive novel molecular targets in AML.     

A versatile planar QCM-based sensor design for nonlabeling biomolecule detection

Despite high theoretical sensitivity, low-cost manufacture, and compactness potentially amenable to lab-on-a-chip use, practical hurdles have stymied the application of the quartz crystal microbalance (QCM) for aqueous applications such as detection of biomolecular interactions. The chief difficulty lies in achieving a sufficiently stable resonance signal in the presence of even minute fluctuations in hydrostatic pressure. In this work, we present a novel versatile planar sensor chip design (QCM chip) for a microliter-scale on-line biosensor. By sealing the quartz resonator along its edges to a flat, solid support, we provide uniform support for the crystal face not exposed to solvent, greatly decreasing deformation of the crystal resonator under hydrostatic pressure. Furthermore, this cassette design obviates the need for direct handling when exchanging the delicate quartz crystal in the flow cell. A prototype 27-MHz sensor signal exhibited very low noise over a range of flow rates up to 100 microL/min. In contrast, signals obtained from a conventional QCM sensor employing an O-ring-based holder were less stable and deteriorated even further with increasing flow rate. Additional control designs with intermediate amounts of unsupported undersurface yielded intermediate levels of stability, consistent with the interpretation that deformation of the crystal resonator under fluctuating hydraulic pressure is the chief source of noise. As a practical demonstration of the design's high effective sensitivity, we readily detected interaction between myoglobin and surface-bound antibody.     

VLS growth of alternating InAsP/InP heterostructure nanowires for multiple-quantum-dot structures

We investigated the Au-assisted growth of alternating InAsP/InP heterostructures in wurtzite InP nanowires on InP(111)B substrates for constructing multiple-quantum-dot structures. Vertical InP nanowires without stacking faults were obtained at a high PH(3)/TMIn mole flow ratio of 300-1000. We found that the growth rate changed largely when approximately 40 min passed. Ten InAsP layers were inserted in the InP nanowire, and it was found that both the InP growth rate and the background As level increased after the As supply. We also grew the same structure using TBAs/TBP and could reduce the As level in the InP segments. A simulation using a finite-difference time-domain method suggests that the nanowire growth was dominated by the diffusion of the reaction species with long residence time on the surface. For TBAs/TBP, when the source gases were changed, the formed surface species showed a short diffusion length so as to reduce the As background after the InAsP growth.     

Transmission electron microscope observation of Si deposited on W(110) surface

The (110) surface of a thin W crystal deposited with Si has been investigated by using a transmission electron microscope (TEM). It was found that an ordered Si–W alloy layer with a regular periodic arrangement of antiphase boundaries (APBs) is formed, as a result of intermixing of deposited Si with the W substrate at room temperature (RT). A crystal structure model of this W–Si superstructure is proposed in this study. After 800°C annealing of Si deposited at RT, grains of tetragonal WSi₂ are formed on the W–Si ordered alloy layer. Grains of WSi₂ are also formed when Si is deposited on a W substrate maintained at 900°C. These WSi₂ grains have epitaxial orientation relationships with the W(110) substrate as follows: (110)W//(01 ) WSi₂ and [001]W//[100]WSi₂.     

Long-term efficacy of a self-retaining intraurethral catheter for the treatment of prostatic obstruction

The aim of the present study was to estimate insulin secretion, insulin sensitivity (SI), and glucose effectiveness at basal insulin (SG) in subjects with bulimia nervosa. Eight bulimic patients and eight age-, body mass index-, and sex-matched healthy control subjects without a family history of diabetes were studied. The subjects all had normal glucose tolerance. They underwent a modified frequently sampled intravenous glucose tolerance test; glucose (300 mg/kg body weight) was administered, and insulin (4 mU/kg body weight/min) was infused from 20 to 25 minutes after administration of glucose. SI and SG were estimated by Bergman's minimal model method. Basal insulin (27 +/- 3 v 45 +/- 3 pmol/L) was significantly lower in bulimic patients than in normal controls (P < .05), but basal glucose was similar between the two groups (4.5 +/- 0.1 v 4.9 +/- 0.1 mmol/L, P > .05). The glucose disappearance rate (KG) and acute insulin response to glucose estimated by the intravenous glucose tolerance test (AIR(glucose)) were similar between the two groups (KG, 1.35 +/- 0.29 v 2.20 +/- 0.21 min(-1), P > .05; AIR(glucose), 2,920 +/- 547 v 2,368 +/- 367 pmol/L x min, P > .05). No significant difference was observed in SI between the two groups (1.34 +/- 0.18 v 1.25 +/- 0.20 x 10(-4) x min(-1) x pmol/L(-1), P > .05). On the other hand, glucose effectiveness at basal (SG) and zero (GEZI) insulin was significantly diminished in comparison to normal controls (SG, 0.011 +/- 0.002 v 0.024 +/- 0.002 min(-1), P < .01; GEZI, 0.008 +/- 0.002 v 0.017 +/- 0.003 min(-1), P < .01). Thus, bulimic patients with normal glucose tolerance without a family history of diabetes were characterized by normal insulin secretion, normal SI, and reduced SG and GEZI.     

The prognostic significance of macroscopic growth pattern of hepatocellular carcinoma

AIM: To investigate the prevalence and amount of polyploidy in fine needle aspiration specimens of the liver, urinary cytospin preparations, and cytospin preparations from pleural and peritoneal fluid. METHODS: Cells from 44 liver smears, 48 urine specimens, and 46 pleural and peritoneal aspirations were examined. After Feulgen restaining the DNA content of 100 randomly selected nuclei was determined using a TAS-plus image analysis system, combined with an automated microscope. RESULTS: Polyploidy was observed up to 16c in the liver, and up to 8c in urothelium and mesothelium. Sixty eight per cent of the liver aspirates contained polyploid nuclei. The rate in urothelium was 20.8% and in mesothelium 6.5%. CONCLUSIONS: Polyploidy in the liver may be interpreted as being associated with tissue differentiation, but the findings in urothelium and mesothelium remain of unknown importance.     

Prostacyclin analog-suppressed ischemia-reperfusion injury of the rat liver: evaluation by calpain mu activation

Advances in perinatal and neonatal health care over the past few decades have resulted in a substantial reduction in perinatal mortality. Some of this improvement has been attributed to antepartum fetal surveillance techniques. The primary objective of antepartum fetal surveillance techniques is to avoid fetal deaths. An ideal secondary objective is to avoid neonatal complications related to intrauterine asphyxia. In this article, some of the difficulties in evaluating existing antepartum fetal surveillance techniques are highlighted. Some of the epidemiological methods for evaluating a screening test are reviewed and their importance discussed with reference to fetal testing procedures. Lastly, the possibility of considering indication-specific fetal testing to improve perinatal morbidity is examined.     

A cross-validation of the European Organization for Research and Treatment of Cancer QLQ-C30 (EORTC QLQ-C30) for Japanese with lung cancer

The EORTC QLQ-C30 was developed in English-speaking cultures. To determine if this instrument could cross a broad cultural divide and be used in Japan, the cross-cultural validity of its Japanese version was estimated. In evaluating psychometric testing, internal consistency by Cronbach's alpha, item-discrimination by multitrait scaling analysis, and validity analysis with ECOG performance score (PS) and Karnofsky Performance Status Scale (KPS) were performed. The QLQ-C30 (version 1.0) was given to 105 patients with lung cancer. Although the response rate was low in patients with PS 4, the questionnaire was well accepted by patients with PS 0-3. The Japanese QLQ-C30 has a weak scale of role functioning in terms of item discriminative validity. It also has a weak scale of cognitive functioning in items of discriminative validity and internal consistency. However, known-groups comparison showed the expected clinical validity with PS for all the scales except for financial impact, and longitudinally clinical validity with KPS was shown in scales of cognitive functioning, fatigue, and nausea and vomiting. Multitrait scaling analysis showed that the predicted scales constituting quality of life (QOL) in the English-speaking culture were extracted from the Japanese QLQ-C30, and found to be valid in Japan, indicating its possible usefulness as an instrument that is universally applicable across cultures.     

Bilateral peripelvic fat simulating renal pelvic tumor

Lipomas are benign tumors which may simulate peripelvic masses and usually originate in the renal cortex or the perirenal adipose tissue. Excessive proliferation of the peripelvic fat of the kidney simulating a renal pelvic tumor was detected in our case, illustrating a rare instance in which the kidney was salvaged.     

Detection of contamination of vaccines with the reticuloendotheliosis virus by reverse transcriptase polymerase chain reaction (RT-PCR)

Phospholipase C (phosphatidylcholine phosphohydrolase, EC 3.1.4.3) and lipase (EC 3.1.1.3) activities were detected in the supernatant fluid of Pseudomonas fluorescens strain D cultures. A combination of ultrafiltration and successive chromatography through columns of Sephadex G-75 and DEAE-cellulose was used to purify the phospholipase C over 700-fold from the culture medium, with 28.5% yield. The purified enzyme appeared as a single band after polyacrylamide gel electrophoresis. The apparent molecular mass of the phospholipase C was 36,000 daltons when estimated by gel permeation chromatography. The purified enzyme hydrolysed phosphatidylcholine more efficiently than phosphatidylethanolamine. The synthetic substrate p-nitrophenylphosphorylcholine, phosphatidylinositol or sphingomyelin were not hydrolysed. Hydrolysis of phosphatidylcholine was inhibited by EDTA (1mM) and stimulated by Zn2+, Mg2+ ions and detergents. These properties of the enzyme indicate that it is distinct from the previously reported Ps. fluorescens phospholipase C.