Fluorescence in situ Hybridization Analysis of 12;21 Translocation in Japanese Childhood Acute Lymphoblastic Leukemia

Fluorescence in situ hybridization (FISH) analysis was applied to detect t(12;21) using two yeast artificial chromosome probes and cosmid probes covering the TEL(ETV6) and the AML1 gene to clarify the incidence of abnormality of t(12;21) in Japanese childhood acute lymphoblastic leukemia (ALL). We detected seven TEL/AML1 fusion positive patients (9.5%), all of whom were diagnosed as B-lineage ALL, among 74 childhood ALL. On the other hand, no TEL/AML1 fusion positive patients were found among 37 adult ALL. The incidence among Japanese seemed to be lower than that among other nations. Of the seven patients with the TEL/AML1 fusion, five exhibited normal karyotype, one was t(8;12)(q11;p13), i(21q) and the remaining one exhibited a near-triploid karyotype in conventional G-banding. The FISH method clearly demonstrated that all patients with the TEL/AML1 fusion had subpopulations of leukemic cells with deletion of the normal TEL allele, which is significant for understanding the progression of leukemia with t(12;21).     

Eicosapentaenoic acid reduces pulmonary edema in endotoxemic rats

BACKGROUND: Recently, eicosapentaenoic acid (EPA) was found to have an anti-inflammatory effect attributable to diminished synthesis of arachidonic acid metabolites that initiate acute lung injury. We evaluated the ability of dietary EPA supplementation to prevent endotoxin-induced acute lung injury in rats. MATERIALS ANS METHODS: Rats fed a standard diet were divided randomly into two groups: for 2 weeks one group additionally was fed 1000 mg/kg/day of EPA ethyl ester emulsion (EPA rats), while in the other group the diet was supplemented with vehicle alone (control rats). Fatty acid components of alveolar macrophages (AM) were measured, as well as leukotriene (LT) B(4) and LTB(5) production by AM exposed in vitro to calcium ionophore A23187. Plasma concentrations of thromboxane (Tx) B(2), a stable metabolite of TxA(2), were examined 1 h after inducing lung injury with endotoxin (2 mg/kg iv). At 6 h, wet/dry (W/D) weight ratios were calculated for the lungs to assess pulmonary edema, and neutrophils were counted in pulmonary parenchyma and peripheral blood. RESULTS: Arachidonic acid content and LTB(4) generation in AM were significantly lower in EPA rats than in controls; conversely, EPA content and LTB(5) generation in AM were significantly higher in the EPA group. Neutrophil counts in lung parenchyma and peripheral blood did not differ between groups, but W/D and plasma TxB(2) concentrations were significantly lower in EPA rats. CONCLUSIONS: EPA supplementation depressed arachidonic acid content and LTB(4) generation in AM and plasma TxB(2) in our model, leading to decreased pulmonary edema.     

Siblings with Idiopathic Left Atrial Appendage Ostial Stenosis and Cor Triatriatum

Isolated left atrial appendage (LAA) ostial stenosis is a very rare entity found coincidentally in adults by transesophageal echocardiography. A 3‐month‐old healthy infant was suspected as having cor triatriatum. His brother had a history of surgical treatment of cor triatriatum. A cardiac catheterization revealed a narrowed ostium of the LAA and confirmed the echocardiographic diagnosis of isolated LAA ostial stenosis. This is the first pediatric case of idiopathic LAA ostial stenosis. The siblings called our attention to the differential diagnosis and the etiopathogenesis between LAA ostial stenosis and cor triatriatum.     

Source apportionment of methane escaping the subsea permafrost system in the outer Eurasian Arctic Shelf

The East Siberian Arctic Shelf holds large amounts of inundated carbon and methane (CH₄). Holocene warming by overlying seawater, recently fortified by anthropogenic warming, has caused thawing of the underlying subsea permafrost. Despite extensive observations of elevated seawater CH₄ in the past decades, relative contributions from different subsea compartments such as early diagenesis, subsea permafrost, methane hydrates, and underlying thermogenic/ free gas to these methane releases remain elusive. Dissolved methane concentrations observed in the Laptev Sea ranged from 3 to 1,500 nM (median 151 nM; oversaturation by ∼3,800%). Methane stable isotopic composition showed strong vertical and horizontal gradients with source signatures for two seepage areas of δ¹³C-CH₄ = (−42.6 ± 0.5)/(−55.0 ± 0.5) ‰ and δD-CH₄ = (−136.8 ± 8.0)/(−158.1 ± 5.5) ‰, suggesting a thermogenic/natural gas source. Increasingly enriched δ¹³C-CH₄ and δD-CH₄ at distance from the seeps indicated methane oxidation. The Δ¹⁴C-CH₄ signal was strongly depleted (i.e., old) near the seeps (−993 ± 19/−1050 ± 89‰). Hence, all three isotope systems are consistent with methane release from an old, deep, and likely thermogenic pool to the outer Laptev Sea. This knowledge of what subsea sources are contributing to the observed methane release is a prerequisite to predictions on how these emissions will increase over coming decades and centuries.

The East Siberian Arctic Shelf (ESAS) is the world’s largest and shallowest shelf sea system, formed through inundation of northeast Siberia during sea level transgression in the early Holocene. The ESAS holds substantial but poorly constrained amounts of organic carbon and methane (CH₄). These carbon/methane stores are contained in unknown partitions as gas hydrates, unfrozen sediment, subsea permafrost, gas pockets within and below the subsea permafrost, and as underlying thermogenic gas (1–3). Methane release to the atmosphere from these compartments could potentially have significant effects on the global climate (4, 5), yet there are large uncertainties regarding the size and the vulnerability toward remobilization of these inaccessible and elusive subsea carbon/methane pools. Conceptual development and modeling have predicted that warming of the ESAS system by a combination of geothermal heat and climate-driven Holocene heat flux from overlying seawater, recently further enhanced by Anthropocene warming, may lead to thawing of subsea permafrost (6, 7). Subsea permafrost drilling in the Laptev Sea, in part at the same sites as 30 y ago, has recently confirmed that the subsea permafrost has indeed come near the point of thawing (8). In addition to mobilization of the carbon/methane stored within the subsea permafrost, its degradation can also lead to the formation of pathways for gaseous methane from underlying reservoirs, allowing further methane release to the overlying water column (3, 9).Near-annual ship-based expeditions to the ESAS over the past two decades have documented widespread seep locations with extensive methane releases to the water column (3, 10). Methane levels are often found to be 10 to 100 times higher than the atmospheric equilibrium and are particularly elevated in areas of strong ebullition from subsea gas seeps (“methane hotspots”). Similarly, elevated dissolved methane concentrations in bottom waters appear to be spatially related to the thermal state of subsea permafrost as deduced from modeling results and/or geophysical surveys (7, 9). Currently, we lack critical knowledge on the quantitative or even relative contributions of the different subsea pools to the observed methane release, a prerequisite for robust predictions on how these releases will develop. An important distinction needs to be made between pools that release methane gradually, such as methane produced microbially in shallow sediments during early diagenesis or in thawing subsea permafrost, versus pools with preformed methane that may release more abruptly once pathways are available, such as from disintegrating methane hydrates and pools of thermogenic (natural) gas below the subsea permafrost. Multidimensional isotope analysis offers a useful means to disentangle the relative importance of these different subsea sources of methane to the ESAS: Stable isotope data (δ¹³C-CH₄ and δD-CH₄) provide useful information on methane formation and removal pathways, and the radiocarbon content of methane (Δ¹⁴C-CH₄) helps to determine the age and methane source reservoir (see SI Appendix, text S1 for details on these isotope systematics and typical isotopic signatures for the ESAS subsea system).Here, we present triple-isotope–based source apportionment of methane conducted as part of the Swedish–Russian–US investigation of carbon–climate–cryosphere interactions in the East Siberian Arctic Ocean (SWERUS-C3) program. To this end, the distribution of dissolved methane, its stable carbon and hydrogen isotope composition, as well as natural radiocarbon abundance signature, were investigated with a focus on the isotopic fingerprint of methane escaping the seabed to pinpoint the subsea sources of elevated methane in the outer Laptev Sea.     

Short Report

Background : Most aphasia therapists appear to assume that people with aphasia undergo psychological distress that is associated with communication problems. However, the relationship between aphasia and psychological status has not been sufficiently investigated. Aim : The aim of this study was to explore the relationship between verbal communication and psychological status in people with aphasia. Methods & Procedure : A total of 25 people with aphasia were assessed by the Observational Profile of Communication (OPC), the Questionnaire of Verbal Communication (QVC), and the Standard Language Test of Aphasia (SLTA). Two items of the OPC—Interpersonal Attitude and Emotional State—were used as measures of psychological status. Two domains of the QVC—Receptive Ability and Expressive Ability—were used as measures of verbal communication activity. The overall scoring system of the SLTA was used to rate the severity of aphasia. Correlations were calculated between the OPC and other variables, namely, Receptive Ability, Expressive Ability, the SLTA, age, and time since onset. The group effects of gender and aphasia type were examined. Outcome & Results : Interpersonal Attitude had a moderate and significant correlation with Receptive Ability, but not with Expressive Ability, the SLTA, age, and time since onset. Emotional State had moderate and significant correlations with the SLTA and time since onset, but not with Receptive Ability, Expressive Ability, and age. Gender and aphasia type did not have a significant relationship with the measures of psychological status. Conclusions : The relationship between verbal communication and psychological status was not straightforward in this small exploratory study. The severity of the communication problem in aphasic people does not necessarily appear to relate to psychological status.     

Evaluation of duodenal hypersensitivity induced by duodenal acidification using transnasal endoscopy

Background and Aim: Although duodenal hypersensitivity has been suggested as one of the causes of functional dyspepsia (FD), a practical method to clarify this has not yet been established. The aim of this study was to evaluate whether patients with FD have duodenal hypersensitivity to acid, using transnasal endoscopy. Methods: In all, 44 patients with FD and 16 healthy volunteers were enrolled, and all the subjects received transnasal endoscopy in the morning after overnight fasting. After ordinary transnasal endoscopy, an infusion tube was introduced into the duodenal bulb by transnasal endoscopy and acid (20 mL, 0.1 N HCl, 20 mL/min, 36.5°C) was injected via the infusion tube. The severity of 12 symptoms was assessed by each subject using a 100‐mm visual analogue scale. The maximum severity scale was defined as the maximum score of the symptom severity scale. The total score was defined as the aggregate score of the maximum severity scale of the 12 symptoms. The maximum severity scales and the total scores between patients with FD and healthy volunteers were evaluated. Results: The maximum severity scales of nine symptoms increased significantly more after acid infusion in patients with FD than in healthy volunteers (P < 0.05). There were significant differences in the total scores (patients with FD vs healthy volunteers 233.8 ± 37.8 vs 63.9 ± 14.6, mean ± standard error of the mean, P < 0.001). Conclusions: Duodenal acidification using transnasal endoscopy enabled the evaluation of duodenal hypersensitivity to acid in healthy volunteers and patients with FD.     

Asymptomatic hyperglycaemia is associated with increased intimal plus medial thickness of the carotid artery

Summary Atherosclerotic changes have not been demonstrated directly in asymptomatic hyperglycaemic non-diabetic subjects, although high mortality due to coronary heart disease has been reported. We measured arterial wall thickness non-invasively, in order to directly demonstrate atherosclerosis of the carotid arteries of hyperglycaemic non-diabetic subjects and to evaluate its risk factors.The thicknesses of the intimal plus medial complex (IMT) of the carotid arteries of 112 asymptomatic hyperglycaemic non-diabetic subjects (aged 22–81, 95 males and 17 females) were compared with those of 55 healthy male subjects and 211 non-insulin-dependent NIDDM male diabetic patients. The subjects were subgrouped into impaired glucose-tolerant (IGT) subjects who had a 2-h glycaemic level of more than 7.8 mmol/l, and non-IGT subjects whose 2-h glycaemic levels were within 6.7–7.7 mmol/l.Non-IGT and IGT subjects showed significantly greater IMTs than age-matched healthy males and showed no significant differences compared to age-matched NIDDM patients. Multivariate analysis demonstrated that the risk factors for IMT of non-IGT and IGT subjects were age and systolic blood pressure. According to data on the accumulation of atherogenic risks (hypertension, dyslipidaemia, and smoking), IMT increased linearly in non-IGT and IGT subjects. However, non-IGT and IGT subjects without hyperlipidaemia, hypertension, or smoking risk still had significantly greater IMT than age-matched normal males (1.019±0.063 vs 0.770±0.111 mm, p<0.05). Prevalence of ECG-indicated coronary heart disease was significantly higher in hyperglycaemic non-diabetic subjects and NIDDM with increased carotid arterial wall thickness (IMT 1.1 mm) than in those without increased thickness (IMT<1.1 mm). Asymptomatic hyperglycaemic non-diabetic subjects have increased thickness of their carotid arteries compared to age-matched male NIDDM patients. As one of several independent risk factors, mild hyperglycaemia advances atherosclerosis, which leads to coronary heart disease.Abbreviations IMT Intimal plus medial complex - NIDDM non-insulin-dependent diabetes mellitus - IGT impaired glucose tolerance - CHD coronary heart disease - T-Chol serum total cholesterol - HDL-C high-density lipoprotein cholesterol - TG serum triglycerides