Abruptly Increased Research Articles

Percolation theory as a conceptual framework to explain spontaneous atrial fibrillation termination: a pilot study.

Atrial fibrillation (AF) strikingly possesses the ability to abruptly transition into more organized electrical activity and spontaneously terminate, even after persisting for long periods. Despite being central to the clinical behavior and treatment of AF, these phenomena remain incompletely understood. In this paper, we hypothesized that the spontaneous termination of AF may represent a type of percolation phase transition, which is more likely to occur when a domain spanning cluster of refractory sites in the atrium are connected (called a 'percolation cluster'). This was assessed in n=50 computational simulations of AF developed using the Aliev-Panfilov (APV) 2-dimensional cell model. In self-terminating simulations of AF, it was found that the average refractory cluster size, χ(p) (median: 647.7), and the largest refractory cluster size, M1 (median: 1702.3), abruptly increased just prior to AF spontaneously terminating, indicating the onset of the formation of a domain spanning percolation cluster. In contrast, simulations of sustained AF did not demonstrate an increase in χ(p) (median: 463.0) and M1 (median: 1448.2). Self-terminating AF simulations also demonstrated hallmark properties characteristic of a percolation phase transition, such as an abrupt increase in χ(p) at the critical occupation probability pc. The cluster size distribution was also shown to obey a power law for various occupation probabilities p, also indicative of a percolation phase transition. Collectively, these properties suggests that the spontaneous termination of AF could be a form of percolation phase transition, which could provide new insights for AF treatment.

Respiratory Rate as a Factor in Lung Injury-Not Just What You Set, but How You Set.

Respiratory Rate as a Factor in Lung Injury-Not Just What You Set, but How You Set.

Salt Marsh Response to Inlet Switch‐Induced Increases in Tidal Inundation

AbstractThere is widespread concern that rapidly rising sea levels may drown salt marshes by exceeding the rate at which these important ecosystems can build elevation. A significant fraction of marshes reside within backbarrier estuaries, yet little attention has been paid to how changes in inlet geometry influences estuarine tides and marshes. In 1898, a coastal storm eroded a new inlet through the barrier beach that fronts the North‐South Rivers Estuary in Massachusetts, USA. The new inlet shortened the North River by 5.6 km and lengthened the South River channel by the same amount. Modern measurements of tidal attenuation suggest that channel shortening abruptly increased mean high tide along the North River by at least 30 cm. Foraminifera communities within North River marsh sediments indicated an environmental change from infrequent to frequent inundation at the time of the 1898 switch in inlet location, which supports this hypothesis. Increased mineral sediment deposition after the inlet switch played a dominant role in allowing marshes along the North River channel to adjust to greater inundation. Following the inlet switch, sediment accreted in North River marshes at 2–5 times the rate of sea level rise (SLR). The North River channel widened by an average of 18% relative to pre‐1898 conditions to accommodate the increased tidal prism. The role of mineral sediment accretion in making this marsh resilient to an abrupt increase in inundation depth highlights the importance of maintaining adequate sediment supplies in coastal regions as SLR accelerates.

Lung Injury Is Induced by Abrupt Increase in Respiratory Rate but Prevented by Recruitment Maneuver in Mild Acute Respiratory Distress Syndrome in Rats.

Gradually changing respiratory rate (RR) during time to reduce ventilation-induced lung injury has not been investigated. The authors hypothesized that gradual, compared with abrupt, increments in RR would mitigate ventilation-induced lung injury and that recruitment maneuver before abruptly increasing RR may prevent injurious biologic impact. Twenty-four hours after intratracheal administration of Escherichia coli lipopolysaccharide, 49 male Wistar rats were anesthetized and mechanically ventilated (tidal volume, 6 ml/kg; positive end-expiratory pressure, 3 cm H2O) with RR increase patterns as follows (n = 7 per group): (1) control 1, RR = 70 breaths/min for 2 h; (2) and (3) abrupt increases of RR for 1 and 2 h, respectively, both for 2 h; (4) shorter RR adaptation, gradually increasing RR (from 70 to 130 breaths/min during 30 min); (5) longer RR adaptation, more gradual increase in RR (from 70 to 130 breaths/min during 60 min), both for 2 h; (6) control 2, abrupt increase of RR maintained for 1 h; and (7) control 3, recruitment maneuver (continuous positive airway pressure, 30 cm H2O for 30 s) followed by control-2 protocol. At the end of 1 h of mechanical ventilation, cumulative diffuse alveolar damage scores were lower in shorter (11.0 [8.0 to 12.0]) and longer (13.0 [11.0 to 14.0]) RR adaptation groups than in animals with abrupt increase of RR for 1 h (25.0 [22.0 to 26.0], P = 0.035 and P = 0.048, respectively) and 2 h (35.0 [32.0 to 39.0], P = 0.003 and P = 0.040, respectively); mechanical power and lung heterogeneity were lower, and alveolar integrity was higher, in the longer RR adaptation group compared with abruptly adjusted groups; markers of lung inflammation (interleukin-6), epithelial (club cell secretory protein [CC-16]) and endothelial cell damage (vascular cell adhesion molecule 1 [VCAM-1]) were higher in both abrupt groups, but not in either RR adaptation group, compared with controls. Recruitment maneuver prevented the increase in VCAM-1 and CC-16 gene expressions in the abruptly increased RR groups. In mild experimental acute respiratory distress syndrome in rats, gradually increasing RR, compared with abruptly doing so, can mitigate the development of ventilation-induced lung injury. In addition, recruitment maneuver prevented the injurious biologic impact of abrupt increases in RR.

Excessively Increased Joint-Line Obliquity After Medial Opening-Wedge High Tibial Osteotomy Is Associated With Inferior Radiologic and Clinical Outcomes: What Is Permissible Joint-Line Obliquity

This study aimed to evaluate the permissible joint-line obliquity (JLO) based on radiologic and clinical outcomes with midterm follow-up after medial open-wedge high tibial osteotomy (MOWHTO). Patients who had undergone MOWHTO from March 2014 to May 2016 were retrospectively evaluated. They were divided into 4 groups based on JLO as represented by postoperative medial proximal tibial angle (MPTA). Radiologic parameters including MPTA, joint-line orientation angle (JLOA), joint-line convergence angle (JLCA), posterior tibial slope, weightbearing line ratio (WBLR), and coronal translation were analyzed. Clinical outcomes were evaluated with American Knee Society Score (AKSS), Western Ontario and McMaster University Index, and short-form 36 health survey (SF-36). The changes between preoperation and final follow-up in JLOA and MPTA were defined as ΔJLOA and ΔMPTA. A total of 135 knees were finally included (MPTA ≤90.32° as group I; 90.33° to 92.62° as group II; 92.74° to 95.22° as group III; and≥95.23° as group IV). The last follow-up MPTA, JLOA, and JLCA values were different between the groups (P < .001, P < .001, and P= .015, respectively). WBLR and JLOA positively correlated with MPTA; however, WBLR showed an abrupt increase at MPTA >96.5°, and the JLOA distribution tended to be greater than the regression line at MPTA >96°. Moreover, ΔJLOA was not as large as ΔMPTA. The percentage of patients attaining a minimal clinically important difference was significantly lower in theAKSS-functional score and SF-36 physical component summary in group IV (P=.008 and 0.021, respectively). The JLOA did not change as much as the MPTA, but an MPTA >95.2° abruptly increased the JLOA and valgus overcorrection after MOWHTO. Poor clinical outcomes were more evident in excessive MPTA (>95.2°) than in mildly undercorrected or properly corrected MPTA (<95.2°). III, retrospective cohort study.

An abrupt Middle-Miocene increase in fluid flow into the Leeward Margin Great Bahama Bank, constraints from δ44Ca and Δ47 values

The advection of seawater into the sediments deposited on the margins of Great Bahama Bank has been demonstrated to play in important role in ventilating the uppermost sediments, as well as supplying elements for diagenetic reactions deeper within the platform. Here, we implement a numerical model to calculate the rate of fluid advection at ODP Site 1003, using calcium isotopes as a tracer for fluid advection. A key parameter for this model, the rate of recrystallization of sediments, was constrained using the clumped isotope proxy. The model was tuned to existing datasets of clumped and carbonate calcium isotope measurements for this site. Results of this modeling effort indicate that, prior to ∼15 Ma, fluids were advected into the platform at a rate substantially lower than the present day. The rate of advection abruptly increased ∼13 Ma to a value greater than the present day. The increase in advective flux during the mid-Miocene coincides with a major reorganization of the platform from a ramp-like geometry to a steeper carbonate platform, indicating a change in the relative contributions of different mechanisms governing fluid flow on the platform margin and interior. This paper aims to explore the utility of using clumped and calcium isotopes to quantitatively reconstruct past fluid advection rates using this novel technique.

Different adaptability of the brown planthopper, Nilaparvata lugens (Stål), to gradual and abrupt increases in atmospheric CO2

Increasing atmospheric CO2 concentrations affect the performances of herbivores. Most previous studies have focused on the effects of abrupt increases in CO2 concentration on herbivore performance, but knowledge about the response of herbivores to gradual increases in CO2 is lacking. We tested the hypothesis that herbivores will show different responses to abrupt and gradual CO2 increases. We measured the performance of the brown planthopper (BPH) (Nilaparvata lugens (Stal)) reared on rice for 15 successive generations under three CO2 levels: ambient CO2 (375 µl/L), a gradual increase in CO2 (25 µl/L increase per generation, 390–750 µl/L), and an abrupt increase in CO2 (750 µl/L). During the first generation, the female and male longevities were affected by both the gradual and abrupt increases in CO2, and the fecundity and net reproductive rate (R0) of the BPH in the abruptly increased CO2 treatment were significantly lower than those in the other two treatments; there were no significant differences in the intrinsic rate of increase (r) and the finite rate of increase (λ) among the three CO2 treatments. After 14 generations, female longevity was significantly prolonged in treatments with both gradual and abrupt CO2 increases. The fecundity of the BPHs reared in the gradual CO2 treatment was significantly higher than that in the other two CO2 treatments. According to the population parameters (r, λ, and R0) and population projection, under a gradual increase in CO2, the BPH population size was higher than that under an abrupt CO2 increase. We concluded that the BPH abundance will increase under a gradual CO2 increase and consequently result in an increase in rice yield loss.

Effects of abrupt salinity increase on nitrification processes in a freshwater moving bed biofilter

The nitrification process is a widely used biological approach responsible for ammonia and nitrite removal in recirculating aquaculture system (RAS) biofilters. Given this pivotal role, the influence of different water quality parameter on nitrification efficiency is important information for RAS operations. One influencing parameter is salinity, and salinity fluctuations in freshwater RAS biofilters are reported to affect the nitrifying bacteria. This study investigated the effects of abrupt increase in salinity in freshwater RAS on substrate-dependent (1’-order) as well as substrate independent (0’-order) nitrification rates. A 100% inhibition was found for surface specific removal (STR) of total ammonia nitrogen (TAN) and surface specific nitrite removal (SNR) when salinity was abruptly increased to 25‰ and above. A fast turnover (i.e. steep decline in [NH4-N+] and [NO2-N−]) were observed at lower salinities (≤10‰), while limited/no degradation of either ammonia or nitrite was seen at salinities above 25‰. At low substrate loading (1’-order process), removal rate constants (k1a) of 0.22 and 0.23 m d-1 were observed for ammonia and nitrite degradation, respectively, declining to 0.01 m d-1when adding marine RAS water increasing the salinity to 15‰. Similar observations followed at high nutrient loadings (0’-order process) with STR and SNR of 0.10 and 0.12 g N m-2 d-1, respectively, declining to 0.01 g N m-2 d-1 at 15‰. When salinities of 25‰ and 35‰ were applied, neither TAN nor nitrite degradation was seen. The results thus demonstrate a pronounced effect of salinity changes when freshwater RAS biofilters are subjected to fast/abrupt changes in salinity. RAS facility operators should be aware of such potential effects and take relevant precautions.

Generation of High-Power Bottle Beams and Autofocusing Beams

We propose and experimentally demonstrate an optical bottle beam (BB) and an abruptly autofocusing beam (AB), which were generated using a ring-Airy beam array. The method can form BB arrays with varying sizes during propagation; consequently, it can produce multiple optical traps. Additionally, the BB size and the AB focal position can be controlled by varying the array radius. The intensity of the resulting beams improved significantly with increasing array number, and the value abruptly increased 800 times at the focal position when array radius and number were 2 mm and 64, respectively. It is the lateral acceleration of Airy beams that causes this abrupt increase in intensity. Numerical simulations were consistent with experimental results. These advantages could be beneficial for potential applications, such as optical traps, laser ablation, and the ignition of nonlinear effect. (The caption of Graphic Abstract is generation of high-power BBs and ABs using a ring-Airy beam array.)

Noncrystalline Titanium Oxide Catalysts for Electrochemical Oxygen Reduction Reactions.

Titanium oxides crystals are widely used in a variety of fields, but little has been reported on the functionalities of noncrystalline intermediates formed in their structural transformation. We measured the oxygen reduction reaction activity of titanium oxide nanoparticles heat-treated for a different time and found that the activity abruptly increased at a certain time of the treatment. We analyzed their structures by using X-ray pair distribution functions with the help of high-resolution transmission electron microscopy and X-ray photoelectron spectroscopy and ascertained that the abrupt increase in the activity corresponded to a structural transformation from a reduced lepidocrocite-type layered titanate to a disordered structure consisting of domains of brookite-like TiO6 octahedral linkages. The further treatment transformed these brookite-like domains into another phase having more edge-sharing sites like the TiO-type cubic structure. This finding would position noncrystalline, disordered structure as a possible origin of the catalytic activity, though nanocrystalline rutile particles might be also considered as the origin.

A Long‐term Study of the Association between the Relative Poverty Rate and Suicide Rate in Japan

The annual number of suicides in Japan totaled around 23,000 in 1997 and abruptly increased to around 31,000 in 1998. This figure has remained high since then. This abrupt increase in the number of suicides was primarily due to an increase in suicides occasioned by economic concerns. The association between various economic factors and suicide must be studied in detail and over the long term in order to ascertain the association between economic concerns and suicide. This study examined the relative poverty rate and the suicide rate in Japan over 30 years and discussed the association between those two rates. The results suggest that the relative poverty rate may be associated with the suicide rate for both sexes. This association is true for men in particular. The organizations and professionals involved in implementing suicide prevention measures should be cognizant of the current findings and consider formulating additional specific measures.

Abstract WP181: Impact Of The Great East Japan Earthquake On Stroke Incidence Among Survivors In Sanriku Coastal Area.

Objective: To examine the effects of tsunami-related lifestyle resulting from the Great East Japan Earthquake on stroke incidence among survivors in Pacific coastal area of Japan. Design: A retrospective study. Setting: Iwate Medical University, Japan. Participants: 4120 Japanese, living in the coastal area who survived from the tsunami disaster. They are living in temporary shelters in 3 major districts of the Sanriku coastal area (Town of Yamada, Otsuchi and Takada). Their clinical data including blood pressure (BP), body mass index (BMI) were examined and compared with those before the tsunami disaster which were examined 12 months before the disaster. Changes of BP and BMI representing tsunami-related lifestyle were analyzed and compared before and after the disaster and correlated with stroke incidence of these 3 areas. Primary outcome measure: Number of stroke patients. Secondary outcome measures: Changes of BP, BMI (body mass index). Results: Levels of BMI before the disaster (23.3kg/m 2 ) continued to increase after 24 months (25.8kg/m 2 ) among survivors in Takada area indicating poor living conditions compared to other areas (p&lt;0.05). Systolic BP (SBP) after 24 months among survivors in Takada area were also higher (158.2+22.4mmHg) compared to that before the disaster (133.4+34.5mmHg) while they were taking anti-hypertensive medications (p&lt;0.05). Stroke incidence among people with increased BMI was abruptly increased from 2.3 to 5.7 patients/month before and after the disaster (p&lt;0.05). Conclusions: Prolonged poor health including increased BP and BMI may contribute to the abrupt increase of stroke incidence 1 year after tsunami disaster.

Invited paper: Dielectric properties of CaCu3Ti4O12 polycrystalline ceramics

We investigated the relationship between the microstructures and dielectric properties of various CaCu3Ti4O12 (CCTO) polycrystalline ceramics sintered in air. An abrupt increase in the dielectric constant (ɛ r) from ∼3,000 to ∼170,000 at 1 kHz occurred with increasing the sintering temperature from 980 to 1000°C for 12 h, respectively, which was accompanied by a very large increase in the average grain size from 5 to 300 µm, respectively, due to an abnormal grain growth. With further increasing the sintering temperature, the ɛ r value at 1 kHz was slightly decreased to ∼150,000 at 1020°C with no variation in the average grain size, significantly decreased to ∼77,000 at 1040°C with a large decrease in the average grain size (∼150 µm), and then maintained the values of ∼76,000 and ∼69,000 at 1060 and 1080°C, respectively, without noticeable variation in the average grain size. While no abnormal grain growth occurred in the CCTO samples sintered at 980°C for the holding time to 24 h and thus their ɛ r values showed relatively lower ɛ r values (< ∼4,000 at 1 kHz), the abnormal grain growth occurred in the samples after a certain holding time at a given sintering temperature of higher than 1000°C and thus their ɛ r values abruptly increased. Analyses by the complex impedance (Z*) and modulus (M*) spectroscopy revealed that the ɛ r values of the CCTO samples were dominantly affected by the electrical properties of grain boundary so that high ɛ r values over 10,000 at 1 kHz were attributable to the high capacitance (C) of grain boundary, which is in good agreement with grain boundary internal barrier layer capacitor (IBLC) model.

Response of dayside auroras to abrupt increases in the solar wind dynamic pressure at positive and negative polarity of the IMF B z component

The optical observations on Heiss Island (Φ′ = 75.0°) have been used to study the characteristics of auroras in the near-noon MLT sector after abrupt increases in the solar wind dynamic pressure at negative and positive polarity of the IMF B z component. It has been found out that the 427.8 and 557.7 nm emission intensities considerably increased at B z 0, fluxes of harder (E > 1 keV) precipitating electrons were superimposed on the soft spectrum of precipitating particles in the equatorial part of the red luminosity band. This red band part was hypothetically caused by the low-latitude boundary layer (LLBL) on closed lines of the geomagnetic field, the estimated thickness of which is ∼3 R e . The 557.7 nm emission intensity increased during 3–5 min after SC/SI and was accompanied by the displacement of the red band equatorward boundary toward lower latitudes. The displacement value was ∼150–200 km when the dynamic pressure abruptly increased by a factor of 3–5. After SC/SI, the 630.0 nm emission intensity continued increasing during 16–18 min. It is assumed that the time of an increase in the red line intensity corresponds to the time of saturation of the magnetospheric boundary layers with magnetosheath particles after an abrupt increase in their density.

Seasonal Variation in Nitrogen and Phosphorus Concentrations in the Mekong River at Vientiane

For delineation of current condition and characteristics of the nutrient concentrations in the Mekong River, continuous frequent observation was carried out in the mainstream at Vientiane. The water samples were taken twice a week from April 2002 to December 2005 and were analyzed for nitrogen and phosphorus species. Detailed seasonal variation characteristics which had not been detected by previous monthly observation were revealed by the frequent observation. Overall, the nutrient concentrations were low, possibly owing to lower population density and lower coverage of agricultural land in the upstream of the sampling point. The ammonium-nitrogen concentration, however, showed an increasing trend during the recent decades. The nitrogen concentrations abruptly increased in May, coinciding with the first small rise in the discharge after the low flow period. It is suggested that the first runoff after the dry season took the accumulated nitrogen in the basin and on the river bed to the river, bringing about the abrupt increase in the nitrogen concentrations. After June, the nitrogen concentrations steadily decreased, regardless of the discharge enhancement during the flood season. It is considered that the nitrogen supply after June was diluted by plentiful water during the flood season. On the other hand, the phosphorus concentrations gently increased from April to June and were greatly fluctuated during the flood season. Continuous dilution effects by the plenty of water and occasional larger scale soil erosions during the flood season may account for the variation characteristics of phosphorus concentrations during the flood season.

Repair of Skin Damage During Fractionated Irradiation with Gamma Rays and Low-LET Carbon Ions

In clinical use of carbon-ion beams, a deep-seated tumor is irradiated with a Spread-Out Bragg peak (SOBP) with a high-LET feature, whereas surface skin is irradiated with an entrance plateau, the LET of which is lower than that of the peak. The repair kinetics of murine skin damage caused by an entrance plateau of carbon ions was compared with that caused by photons using a scheme of daily fractionated doses followed by a top-up dose. Right hind legs received local irradiations with either 20 keV/microm carbon ions or gamma rays. The skin reaction of the irradiated legs was scored every other day up to Day 35 using a scoring scale that consisted of 10 steps, ranging from 0.5 to 5.0. An isoeffect dose to produce a skin reaction score of 3.0 was used to obtain a total dose and a top-up dose for each fractionation. Dependence on a preceding dose and on the time interval of a top-up dose was examined using gamma rays. For fractionated gamma rays, the total dose linearly increased while the top-up dose linearly decreased with an increase in the number of fractions. The magnitude of damage repair depended on the size of dose per fraction, and was larger for 5.2 Gy than 12.5 Gy. The total dose of carbon ions with 5.2 Gy per fraction did not change till 2 fractions, but abruptly increased at the 3rd fraction. Factors such as rapid repopulation, induced repair and cell cycle synchronization are possible explanations for the abrupt increase. As an abrupt increase/decrease of normal tissue damage could be caused by changing the number of fractions in carbon-ion radiotherapy, we conclude that, unlike photon therapy, skin damage should be carefully studied when the number of fractions is changed in new clinical trials.

Microfacies of detrital event layers deposited in Quaternary varved lake sediments of the Piànico‐Sèllere Basin (northern Italy)

AbstractA Quaternary interglacial lake sediment record from the Piànico‐Sèllere Basin (northern Italy) consists of biochemical calcite varves with intercalated detrital layers. At the end of the Piànico Interglacial, continuous varve formation was replaced by predominantly detrital sedimentation. However, 427 varve‐years before this shift, an abrupt increase in the frequency and thickness of detrital layers occurred. Microfacies analyses reveal a total of 152 detrital layers, ranging from 0·2 to 20·15 mm in thickness, deposited during the last 896 years of the Piànico Interglacial. Three microfacies types are distinguished: (i) graded layers, (ii) non‐graded silt layers, and (iii) matrix‐supported layers. The position of detrital layers within an individual varve provides additional information on the season in which they have been deposited. Microfacies analyses in combination with varve counting further enabled precise varve‐to‐varve correlation of the detrital layers for two sediment sections cropping out ca 130 m apart. The detailed intra‐basin correlation allows the source regions of detrital layers to be inferred. Moreover, micro‐erosion at sub‐millimetre scale has been established. Of the described facies types, only the accumulation of summer and spring graded and non‐graded silt layers abruptly increased before the end of interglacial varve formation whereas non‐graded winter silt and matrix‐supported layers are randomly distributed over the entire study period. Heavy rainfalls are assumed to have triggered spring and summer graded layers, so that the occurrence of these layers is thought to be a proxy for extreme precipitation events in the past.

In Acute Promyelocytic Leukemia (APL) with Multiple Relapses Additional Prognostic Information Is Provided by FLT3 and Telomerase (hTERT) Quantitative Real-Time PCR.

The present study, carried out in two APL with multiple relapses, was aimed at determining 1) which correlation does exist between FLT3/hTERT expression levels and PML-RARA results; 2) whether high FLT3 and hTERT expression levels might be predictive of relapse; 3) whether FLT3 expression is better than FLT3 Internal Tandem Duplication (ITD) for evaluating disease outcome. Relative quantifications of FLT3/hTERT transcripts were performed by real-time PCR using SybrGreen I. For FLT3 calibration total RNA from a normal subject was used, for hTERT total RNA from K562 cells. In both cases the ΔΔCt method was used for quantification. On clinical diagnosis one patient with a WBC of 124.0x109/L and a PML-RARA fusion at PML BCR1 presented the FLT3/hTERT genes highly expressed. On qualitative PCR the patient also showed the ITD of FLT3. He was treated with the AIDA protocol and succeeded in achieving a haematological but not molecular remission. During CR FLT3/hTERT expression remained high and the ITD was never detected. Fourteen months later when on first clinical relapse FLT3 expression abruptly increased, the ITD reappeared, hTERT levels were still high. A re-induction chemotherapy induced a second haematological but not molecular remission lasting five months. FLT3 as well as hTERT expression levels became similar to those of the control, and FLT3 ITD disappeared. A progressive increase of FLT3 expression and an abrupt increase of hTERT expression preceded the second relapse which was accompanied by the reappearance of the ITD. After re-induction chemotherapy FLT3/hTERT expression dropped down to values of the control. A third CR was obtained but the patient remained PML/RARA and Flt3 ITD positive and soon after died of a CNS relapse.The other patient was treated in another Centre and came to our observation in haematological CR. At that time he was PML-RARA negative with high FLT3/hTERT expression. Eight months later he was still in clinical but not molecular CR having a PML-RARA fusion at BCR3, high FLT3/hTERT expression levels and presenting FLT3 ITD. One month later when clinical relapse occurred FLT3 expression levels were unchanged, hTERT expression dropped down to normal values and FLT3 ITD was still present. A re-induction chemotherapy induced a second CR with alternatively positive and negative PML-RARA results, high FLT3 and low hTERT expression levels. The patient underwent an allogeneic bone marrow transplant from an unrelated donor but five months later he relapsed for the second time with an abrupt rise of hTERT expression that preceded a quick increase of FLT3 expression. A third clinical but not molecular CR was achieved after chemotherapy, but the patient remained PML-RARA positive with a normal FLT3/hTERT expression. Two months later a rapid increase of hTERT expression preceded that of FLT3 and the occurrence of the third relapse.In conclusion i) increased FLT3 and hTERT levels during CR are associated with alternative positive/negative PML-RARA results on nested RT PCR and are always predictive of pending relapse; ii) on disease recurrence a marked elevation of hTERT expression often preceded that of FLT3; iii) quantitative real-time PCR of the FLT3 gene was more effective in predicting disease outcome than the ITD, this last being discovered only when FLT3 expression was already high.

Seroprevalence of Helicobacter pylori in school-aged Chinese in Taipei City and relationship between ABO blood groups.

To explore the seropositive rate of antibodies against H. pylori (anti-HP) in Taipei City and to compare the relationship of ABO blood groups and H. pylori infection. In 1993, high school students in Shih-Lin District were randomly selected for blood samplings by their registration number at school. In addition, similar procedures were performed on the well-children clinics of Taipei Veterans General Hospital. Besides, randomly selected sera from the adults who took the physical examination were recruited for evaluation. Informed consents were obtained from all the subjects before blood samplings and parents were simultaneously informed for those who were younger than 18-year-old. Blood tests for anti-HP and ABO blood groupings were performed by enzyme-linked immunosorbent assay. Chi square tests were used for the comparisons between seroprevalence of H. pylori and ABO blood groups. Totally, 685 subjects were recruited (260 children aged 1-14 years, 425 high school students aged 15-18 years) were evaluated, and another 88 adult healthy volunteers were studied as well for comparison. The age-specific seropositive rate of anti-HP was 1.3 % at age 1-5 years, 7.7 % at age 6-10 years, and 11.5 % at age 11-14 years. The seroprevalence of H. pylori infection was abruptly increased in young adolescence: 18.6 % at age 15 years, 28.1 % at age 16 years, 32.4 % at age 17 years and 41.0 % at age 18 years, respectively. In the 425 high school students, ABO blood groupings were performed, which disclosed 48.5 % (206/425) of blood group O, 24 % (102/425) of blood group A, 21.8 % (93/425) of blood group B and 5.6 % (24/425) of blood group AB. In comparison of the subjects with blood group O and the other blood groups, no statistical significance could be identified in the seroprevalence of H. pylori (P=0.99). The seroprevalence of H. pylori infection in Taipei City in adults is similar to the developed countries, and the abrupt increase of H. pylori during high school may be resulted from marked increase of interpersonal social activities. Although blood group O was reported to be related to H. pylori infection in previous literature, we found no association between H. pylori infection and ABO blood groups.

Conformation of apolipoprotein E both in free and in lipid-bound form may determine the avidity of triglyceride-rich lipoproteins to the LDL receptor: structural and kinetic study

Slow refolding of human apolipoprotein E (apoE) in solution after guanidine- or cholate-induced denaturation followed by dialysis under controlled conditions was investigated using various spectroscopic properties of fluorescein- and dansyl-labeled apolipoprotein molecules. The results suggest that the last phase(s) of apoE refolding in solution include a slow (several hours at 24°C) interconversion of a self-associated ‘open’ conformer into a more dense ‘closed’ conformer. The hydrophobic interactions are primarily responsible for the formation of this more compact apoE structure. To visualize the contribution of apolipoprotein conformation and/or the number of ‘active’ lipid-bound apoE molecules in the reaction of binding to the low density lipoprotein receptor (LDLr) by solid-phase binding assay, the complexes of human plasma apolipoprotein or recombinant ( rec) apoE3 with dipalmitoylphosphatidylcholine (DPPC) or palmitoyloleoylphosphatidylcholine (POPC) varying in size were used. For seven complexes with plasma protein (four DPPC and three POPC complexes), the final phosphatidylcholine (PC)/protein mole ratio ranged from 117 to 279; affinity constant K a averaged for both PCs and plotted against this ratio abruptly increased from 3.8×10 7 to 3.8×10 8 M −1 with a transition midpoint of 150–180 PC/apoE, mole ratio. Two DPPC complexes with rec protein bind much more efficiently. Complexes with both plasma and rec apoE were able to compete with very low density lipoproteins (VLDL) or low density lipoproteins (LDL) isolated from patients with E3/3 phenotype, for binding to the LDLr. Again, the competition efficiency abruptly increased at the increase in PC content with a transition midpoint of 130 PC/apoE, mole ratio. The transitions observed both in direct and competitive binding assay probably correspond to the abrupt increase in the number of ‘active’ apoE molecules on the complex surface accompanying the change in the size and/or in the shape of the complexes. The efficiency of apoE and apoB as the corresponding major ligands in the binding reaction of VLDL and LDL to the LDL receptor was compared. VLDL bind to LDLr following a simple encounter complex model, while LDL binding was characterized by a more complex two-step model with an additional isomerization step. The analysis of the binding data led us to suggest the existence of the continuum from several (2–3) apoE molecules on the surface of TG-rich particles that resulted in the increased binding affinity, on average 3.5-fold higher, compared to LDL. The existence of a complex equilibrium between aqueous and different lipid-bound forms of apoE is proposed, in particular, the formation of a transient disc-lipoprotein particle structure during the interaction with LDLr in vivo as well as in LPL-stimulated lipolysis of the lipid phase of the particle.