Next-generation sequencing with a myeloid gene panel in core-binding factor AML showed KIT activation loop and TET2 mutations predictive of outcome.

Clinical outcome and mutations of 96 core-binding factor acute myeloid leukemia (AML) patients 18-60 years old were examined. Complete remission (CR) after induction was 94.6%. There was no significant difference in CR, leukemia-free-survival (LFS) and overall survival (OS) between t(8;21) (N=67) and inv(16) patients (N=29). Univariate analysis showed hematopoietic stem cell transplantation at CR1 as the only clinical parameter associated with superior LFS. Next-generation sequencing based on a myeloid gene panel was performed in 72 patients. Mutations in genes involved in cell signaling were associated with inferior LFS and OS, whereas those in genes involved in DNA methylation were associated with inferior LFS. KIT activation loop (AL) mutations occurred in 25 patients, and were associated with inferior LFS (P=0.003) and OS (P=0.001). TET2 mutations occurred in 8 patients, and were associated with significantly shorter LFS (P=0.015) but not OS. Patients negative for KIT-AL and TET2 mutations (N=41) had significantly better LFS (P<0.001) and OS (P=0.012) than those positive for both or either mutation. Multivariate analysis showed that KIT-AL and TET2 mutations were associated with inferior LFS, whereas age ⩾40 years and marrow blast ⩾70% were associated with inferior OS. These observations provide new insights that may guide better treatment for this AML subtype.

Biofortification of rice with lysine using endogenous histones.

Rice is the most consumed cereal grain in the world, but deficient in the essential amino acid lysine. Therefore, people in developing countries with limited food diversity who rely on rice as their major food source may suffer from malnutrition. Biofortification of stable crops by genetic engineering provides a fast and sustainable method to solve this problem. In this study, two endogenous rice lysine-rich histone proteins, RLRH1 and RLRH2, were over-expressed in rice seeds to achieve lysine biofortification. Their protein sequences passed an allergic sequence-based homology test. Their accumulations in rice seeds were raised to a moderate level by the use of a modified rice glutelin 1 promoter with lowered expression strength to avoid the occurrence of physiological abnormalities like unfolded protein response. The expressed proteins were further targeted to protein storage vacuoles for stable storage using a glutelin 1 signal peptide. The lysine content in the transgenic rice seeds was enhanced by up to 35 %, while other essential amino acids remained balanced, meeting the nutritional standards of the World Health Organization. No obvious unfolded protein response was detected. Different degrees of chalkiness, however, were detected in the transgenic seeds, and were positively correlated with both the levels of accumulated protein and lysine enhancement. This study offered a solution to the lysine deficiency in rice, while at the same time addressing concerns about food safety and physiological abnormalities in biofortified crops.

Atmospheric measurements of the physical evolution of aircraft exhaust plumes.

Drawing from a series of field measurement activities including the Alternative Aviation Fuels Experiments (AAFEX1 and AAFEX2), we present experimental measurements of particle number, size, and composition-resolved mass that describe the physical and chemical evolution of aircraft exhaust plumes on the time scale of 5 s to 2-3 min. As the plume ages, the particle number emission index initially increases by a factor of 10-50, due to gas-to-particle formation of a nucleation/growth mode, and then begins to fall with increased aging. Increasing the fuel sulfur content causes the initial increase to occur more rapidly. The contribution of the nucleation/growth mode to the overall particle number density is most pronounced at idle power and decreases with increasing engine power. Increasing fuel sulfur content, but not fuel aromatic content causes the nucleation/growth mode to dominate the particle number emissions at higher powers than for a fuel with "normal" sulfur and aromatic content. Particle size measurements indicate that the observed particle number emissions trends are due to continuing gas-to-particle conversion and coagulation growth of the nucleation/growth mode particles, processes which simultaneously increase particle mass and reduce particle number density. Measurements of nucleation/growth mode mass are consistent with the interpretation of particle number and size data and suggest that engine exit plane measurements may underestimate the total particle mass by as much as a factor of between 5 and 10.

Nitric oxide synthase neurons in different areas of normal aged and Alzheimer's brains.

This study investigated the distribution of nitric oxide synthase-containing neurons in the cerebral cortex of individuals with Alzheimer's disease, and compared them with age-matched controls. Paraffin-embedded sections of the frontal (area 10), occipital (area 17) and entorhinal cortices (area 28), and hippocampal formation obtained from 13 autopsy cases were used in the study. Neurons expressing nitric oxide synthase messenger RNA and protein were identified, respectively, by in situ hybridization and immunohistochemistry. Optical densities of nitric oxide synthase-positive neurons were assessed in 50 randomly selected fields of each of the above regions of the cortices, in each case by microscopic photometry. In the frontal cortex of the Alzheimer group, while a decrease in the number of nitric oxide synthase-positive neurons was evident, the nitric oxide synthase neurons, on the other hand, showed an increased optical density in layers II-IV when compared with those of normal ageing. In the occipital cortices, no significant differences in optical density were recorded between the normal ageing and Alzheimer specimens. In the entorhinal cortex, the optical densities of nitric oxide synthase neurons were again similar between the Alzheimer and age-matched control groups. In the hippocampar formation itself, there was an increase of nitric oxide synthase staining in the Alzheimer patients. These results show that (i) nitric oxide synthase neurons are abundant in the human cortex, (ii) the distribution of nitric oxide synthase neurons differs between different cortical regions, and (iii) there are differences between normal ageing and Alzheimer patients in the frontal cortex and the hippocampus.

Reactive hemophagocytic syndrome in childhood--frequent occurrence of atypical mononuclear cells.

Reactive hemophagocytic syndrome, which is characterized by systemic proliferation of benign hemophagocytic histiocytes, usually presents as an acute febrile illness with pancytopenia and hepatosplenomegaly. The commoner diseases associated with the syndrome are infection and malignant lymphoma. In this report, eight cases of reactive hemophagocytic syndrome occurring in infants and young children are described. Unlike the disease occurring in adults, there is frequent occurrence of atypical mononuclear cells both in the peripheral blood and bone marrow. The morphological spectrum of these atypical cells is however still within that seen in infectious mononucleosis, and their reactive nature is substantiated by their spontaneous disappearance and subsequent recovery of the patients. It is important to distinguish this reactive proliferation from the neoplastic cells of 'malignant histiocytosis' or malignant lymphoma, since cytotoxic drugs are not warranted for treatment of this non-neoplastic condition.

Evaluation of a low-cost automatic counting system for nuclear track detectors.

This paper describes a low-cost automatic counting system for recognising and counting microscopic track holes in plastic nuclear track detectors. The hardware includes an Olympus BH2 microscope, (manufactured by the Olympus Optical Company, Japan) a Philips resistive gate sensor (RGS) board, (manufactured by the Philips Company, Netherlands) a frame-grabber board and an IBM PC compatible. The RGS board acts like a camera, sending analog video signals of the microscope's field image to the frame-grabber, which produces a digital image with a resolution of 256 x 256 pixels and 128 grey levels in about 20 ms. This is then stored in either one of two 64K on-board RAMs for processing by the PC. The software is menu-driven and allows image grabbing, saving, loading and processing. The image processing can be divided into three parts namely: segmentation, speckle elimination and the removal of ill-formed track holes. In this paper we will present the results of testing the system with sample images obtained from CR-39 plastic nuclear track detectors. The limitations of the system for counting track holes on these detectors will be discussed.

Effect of endothelin-1 on the vascular smooth muscle cell cycle.

Rabbit vascular smooth muscle cells were cultured in various concentrations of endothelin-1 (ET-1) at 37 degrees C for 24 h. The vascular smooth muscle cell cycle distribution was determined by flow cytometry according to DNA content. In the control group, the mitotically active phase (S + G2 + M phase) of vascular smooth muscle cells was 11.94%. In ET-1-cultured smooth muscle cells, the mitotically active phase was 11.69% at a concentration of 1 pM ET-1, whereas the mitotically active phases were 18.98 and 26.91% at concentrations of 0.1 and 10 nM ET-1, respectively. The findings show that ET-1 significantly increased mitotic activity of cultured vascular smooth muscle cells.

Four documented cases of eosinophilic meningoencephalitis due to Angiostrongylus cantonensis in Hong Kong.

4 cases of eosinophilic meningoencephalitis in Hong Kong are described. The major clinical features of the patients, who were 2-60 years old, were low grade fever, headache, mild meningeal signs, right facial palsy or hemiplegia. Eosinophilia in the peripheral blood and eosinophilic pleocytosis were prominent. Computerized tomography scans of brain showed a small area of attenuation with surrounding hypodense area; the lesion was resolved 1-2 months after admission to hospital. Electroencephalograms revealed abnormally slow dysrhythmia. Sections of a nematode observed in the brain of a patient who died were identified as those of young adult Angiostrongylus cantonensis. High ELISA titres against the crude antigens of this nematode were also noted in the serum of 3 patients. The disease is probably under-recognized in Hong Kong.

Ristocetin-induced platelet agglutination in four Chinese patients with Glanzmann's thrombasthenia.

We studied the degree of Ristocetin-induced platelet agglutination in 4 Chinese patients with Glanzmann's thrombasthenia. At Ristocetin concentrations of 1.2-2.0 mg/ml (final concentration) variable, abnormal responses were observed. The most notable feature in 3 of 4 patients studied was the phenomenon of dose dependent, cyclic platelet agglutination-disagglutination. However, this phenomenon could be reproduced in only one of the 2 patients who were investigated on 2 separate occasions. Variable, but often characteristic responses of thrombasthenic platelets to different concentrations of Ristocetin are a useful additional diagnostic marker for this disease.

Simultaneous glottic and supraglottic laryngeal webs: report of a case.

In a rare case of simultaneous glottic and supraglottic webbing a tantalum keel, as described by McNaught, and a silcone elastomer keel, as described by Montgomery, were placed simultaneously via laryngofissure. Use of different materials appeared to have no bearing on the final, successful outcome.