Prognostic impact of a reduction in the fibrosis-4 index among patients hospitalized with acute heart failure.

Although the fibrosis-4 index (FIB-4) is associated with right atrial pressure or prognosis in acute heart failure (AHF), the prognostic impact of its reduction during hospitalization remains uncertain. We included 877 patients (age, 74.9 ± 12.0 years; 58% male) hospitalized with AHF. The reduction in FIB-4 was defined as: (FIB-4 on admission-FIB-4 at discharge)/FIB-4 on admission × 100. Patients were divided into low (< 1.0%, n = 293), middle (1.0-27.4%, n = 292), and high (> 27.4%, n = 292) FIB-4 reduction groups. The primary outcome was a composite of all-cause death or heart failure rehospitalization within 180 days. The median FIB-4 reduction was 14.7% (interquartile range - 7.8-34.9%). The primary outcome was observed in 79 (27.0%), 63 (21.6%), and 41 (14.0%) patients in the low, middle, and high FIB-4 reduction groups, respectively (P = 0.001). Adjusted Cox proportional-hazards analysis revealed that the middle and low FIB-4 reduction groups were associated with the primary outcome, independent of the pre-existing risk model including baseline FIB-4 ([high vs. middle] hazard ratio [HR]: 1.70, 95% confidence interval [CI]: 1.10-2,63, P = 0.017; [high vs. low] HR: 2.16, 95% CI 1.41-3.32, P < 0.001). FIB-4 reduction provided additional prognostic value to the baseline model, including well-known prognostic factors ([continuous net reclassification improvement] 0.304; 95% CI 0.139-0.464; P < 0.001; [integrated discrimination improvement] 0.011; 95% CI 0.004-0.017; P = 0.001). Additionally, the combination of the reduction in FIB-4 and brain natriuretic peptide was useful for risk stratification. In conclusion, among patients hospitalized with AHF, a greater FIB-4 reduction during hospitalization was associated with better prognoses.

Adsorption efficiency of natural materials for low-concentration cesium in solution.

In this study, several natural materials were investigated in order to clarify their potential use as cesium (Cs) adsorbents in situ. Four materials--carbonized rice hull, beech sawdust, oak sawdust, and charcoal (Japanese cedar)--which were previously shown to have Cs adsorption capabilities, were examined. Cs adsorption experiments were conducted using different initial Cs and adsorbent concentrations. The physical properties, adsorption isotherms, and adsorption processes were then examined, so as to exploit the Cs adsorption characteristics in the field. Based on these findings, carbonized rice hull and beech sawdust were selected as effective Cs adsorbents. It was found that these materials show continuous and stable Cs adsorption rates for different initial Cs concentrations. The adsorption efficiency of these two adsorption materials in combination was considered, and it was shown that the adsorption isotherms for carbonized rice hull and beech sawdust follow the Freundlich model. Furthermore, the beech sawdust adsorption process exhibited better agreement with the calculated values obtained via the adsorption rate model and the adsorption kinetics model than did the carbonized rice hull adsorption.

Surface discharge of heavy metals from low farmland.

Runoff heavy metals from farmland were examined using the field data for the summer of 2005. The observation farmland is located on lowland where the irrigation water was contaminated with the drained water from the upstream farmlands. The area of the farmland is 11.2 ha, of which 6.0 ha and 4.5 ha have been used for rice paddy fields and soybean cultivation, respectively. During the observation, heavy metal concentrations at the downstream end were usually found to be higher than those in the irrigation water. That is, the heavy metal concentrations increased due to the passage of the water through the farmland. This increase in the heavy metal concentrations is not equal to the discharge of the heavy metal because the evaporation on the surface of the paddy field and the absorption by plants makes the surface water volume small. The discharged load from the farmland generally indicates the gross surface load from the farmland. When the effects of circulation irrigation on the heavy metal concentrations are estimated, the discharged load from the farmland should be calculated as the net surface load. When the runoff heavy metals from the circulation irrigation farmland are estimated, it is important to consider the inflowing heavy metals with irrigation water. All the heavy metal types observed in this study were discharged from the farmland. The net surface loads of Cr, Fe, Cd, and Pb were 371 microg m(-2) day(-1), 14.9 mg m(-2) day(-1), 0.26 microg m(-2) day(-1), and 3.3 microm( -2) day(-1), respectively.

Effects of methyl paraben on skin keratinocytes.

Some ingredients of dermatological formulations result in skin irritation and allergy. In particular, preservatives have been reported extensively as a cause of allergic contact dermatitis. The study focused on parabens which have been used extensively as antimicrobial preservatives in foods, drugs and cosmetics. The aim of this study was to clarify the effects of the daily use of methyl paraben (MP) on human skin. The concentrations of MP in the stratum corneum (SC) of the human forearm were measured using the cup method and GC-MS after daily applications of MP containing formulations. The study also investigated the effects of long-term exposure to MP on keratinocytes in vitro. Normal human keratinocytes and the skin equivalents were cultured in the medium containing MP. The following changes were analysed: proliferating ability, apoptotic cells, morphological changes, mRNA and protein expressions. After 1 month of daily applications of MP containing formulations, MP remained unmetabolized and persisted slightly in the SC. MP decreased the proliferating ability of keratinocytes and changed the cell morphology. MP also decreased the expressions of hyaluronan synthase 1 and 2 mRNAs and type IV collagen. In contrast, it increased the expressions of involucrin and HSP27. Furthermore, MP influenced the epidermal differentiation of the skin equivalent. These results suggest that MP exposure through application of dermatological formulations results in MP persistence and accumulation in the SC, and that MP might influence the aging and differentiation of keratinocytes.

Nitrogen removal function of recycling irrigation system.

The purpose of this study was to clarify the nitrogen (N) purification capacity of a paddy field in a recycling irrigation system. Irrigation water was sampled at 12-h intervals during the irrigation period from April to September 2003. In addition, ponded water in a paddy field was collected at three points (inlet, centre and outlet). Total amounts of N were 30.7 kg ha(-1) in inflow and 27.8 kg ha(-1) in outflow. Thus, the net outflow load was -2.9 kg ha(-1). The N removal rate constant when N removal is expressed as a 1st-order kinetic was 0.017-0.024 m d(-1). This value is close to values of wetlands and paddy fields in the literature. We found a good correlation between recycling ratio and N removal effect. These results indicate that the recycling irrigation system accumulates N in the irrigation/drainage system, and thus the paddy field does a good job of water purification by removing N.

Economic valuation of reduction in nitrogen outflow from a paddy field area equipped with a recycling irrigation facility.

We estimated the reduction in nitrogen outflow load from a paddy field that had a recycling irrigation facility and, by using a replacement cost method, evaluated the economic effect of nitrogen removal by the paddy field during the irrigation period in the Yoshinuma region of Tsukuba City, Japan. The recycling ratio of outflow water (proportion of outflow reused) was 13.5%. The nitrogen (N) outflow load was reduced by about 45 kg ha(-1) by the N removal function of the paddy field and by about 39 kg ha(-1) by the recycling irrigation facility. The paddy field equipped with a recycling irrigation facility as an N removal facility was valued at 32.6 million Japanese yen (JPY) ha(-1) and 0.72 million JPY ha(-1) per year, which compare it with the construction and maintenance costs, respectively, of a water quality improvement facility. The recycling irrigation facility was costed at 17.3 million JPY ha(-1) for construction and 0.21 million JPY ha(-1) for maintenance per year. The cost for constructing and maintaining a recycling irrigation facility was 53% of the value of the paddy field area equipped with a recycling irrigation facility as an N removal facility.

Ictal monoparesis associated with lesions in the primary somatosensory area.

Reported are three patients with ictal monoparesis of an arm. In the hemisphere contralateral to the monoparesis, ictal and interictal epileptiform discharges were observed in the centroparietal area, and a well-circumscribed lesion was commonly present in the primary arm somatosensory area (SI). In the presence of an SI lesion, the epileptic activity at the sensorimotor area could lead to selective or predominant activation of the inhibitory motor system.

Long-term effect of bone marrow transplantation in adult-onset adrenoleukodystrophy.

We report a long-term outcome of motor function in a patient with adult-onset adrenoleukodystrophy after bone marrow transplantation (BMT). Clinically motor function gradually improved and became almost normal in 2 years after BMT. Serial transcranial magnetic stimulation showed gradual improvement of central motor conduction until 1 year after BMT, and then it became stable. Central motor conduction time and motor threshold were useful for monitoring the central motor function in this patient.

Nutrient balance in a paddy field with a recycling irrigation system.

We studied nutrient balance in a paddy field that had a recycling irrigation system and evaluated the effect of the irrigation system on nutrient balance during the irrigation period, from April to August 2002. Chemical fertilizer was the main input of phosphorus; the soil absorbed about 56% of it. The amount of nitrogen supplied by the irrigation system was higher than in a representative paddy field, and the amount of nitrogen fertilizer used was decreased because the irrigation water was partly reused. About 20% of applied nitrogen was lost by denitrification. The net outflows of phosphorus and nitrogen were -0.37 and -3.98 kg ha(-1), respectively. These results indicate that our study paddy field performed well in removing phosphorus and nitrogen compounds from runoff water. A recycling irrigation system can be considered an effective way of reducing the amounts of water and fertilizer used and reducing the outflow nutrients.

Dominance of ipsilateral corticospinal pathway in congenital mirror movements.

OBJECTIVE: To clarify the mechanism of congenital mirror movements. DESIGN: The triple stimulation technique (TST) and the silent period were used to investigate a patient with congenital mirror movements. The TST was used to calculate the ratio of ipsilateral to contralateral corticospinal tracts from the two hemispheres to the spinal motor neurones. RESULTS: Transcranial magnetic stimulation over unilateral M1 induced larger ipsilateral than contralateral motor evoked potentials on both sides. Only 9% of spinal motor neurones innervating the abductor digitorum minimi were excited by contralateral primary motor cortex (M1) stimulation, while 94% were excited by the ipsilateral M1 stimulation. The silent period was examined during mirror movements and with voluntary contraction of the right first dorsal interosseus mimicking mirror movements. Left M1 stimulation (through the crossed corticospinal tract) did not show any difference in silent period between the two conditions, while right M1 stimulation (through the uncrossed tract) caused a longer silent period during mirror movements than during voluntary contractions. CONCLUSIONS: The results suggest that mirror movements may be caused by a strong connection between ipsilateral M1 and the mirror movements conveyed through a dominant ipsilateral corticospinal pathway.

Improvement of central motor conduction after bone marrow transplantation in adrenoleukodystrophy.

The case is described of a 20-year-old man with adrenoleukodystrophy who showed right spastic hemiparesis and gait disturbance. Brain magnetic resonance imaging disclosed predominant involvement of the left corticospinal pathway. The clinical symptoms improved after bone marrow transplantation. Transcranial magnetic stimulation disclosed significant improvement in various parameters of central motor conduction.

Requirement of Syk-phospholipase C-gamma2 pathway for phorbol ester-induced phospholipase D activation in DT40 cells.

BACKGROUND: Treatment of many cell types with phorbol esters stimulates phospholipase D (PLD) activity implying regulation of the enzyme by protein kinase C. Studies of the effects of several protein-tyrosine kinase (PTK) inhibitors have suggested that PTK(s) play some roles in the phorbol ester-induced PLD activation, but it remains unclear how and which PTK(s) is involved in this pathway. In this study, we investigated the roles of Syk and other PTKs for the phorbol esters, 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced PLD activation in K562 and DT40 cells. RESULTS: TPA-induced PLD activation was remarkably reduced in both Syk dominant negative mutant K562 cells and Syk deficient DT40 B cells. Mutational analysis further indicated that two major autophosphorylation sites (Tyr-518 and Tyr-519) of Syk are critical for PLD activation. Similarly, TPA-induced PLD activation was reduced in Btk deficient cells, but unaffected in Lyn deficient cells. Finally, in cells deficient in the PLC-gamma2, one of the phosphorylated substrates regulated by Syk and Btk, TPA-induced PLD activation, as well as phosphatidylinositol 4,5-bisphosphate (PIP2) hydrolysis was remarkably reduced. CONCLUSIONS: We demonstrated that the Syk, Btk and PLC-gamma2 pathways are required for TPA-induced PLD activation in DT40 cells.

Characterization of complex chromosomal abnormalities in B-cell lymphoma by a combined spectral karyotyping (SKY) analysis and fluorescence in situ hybridization (FISH) using a 14q telomere probe.

We report a case of non-Hodgkin's lymphoma of unknown origin with invasion into bone marrow and brain. This case showed complex chromosomal abnormalities, including five clonal marker chromosomes (mar) and four additional materials of unknown origin (add) that could not be identified by means of conventional G-banding. Spectral karyotyping (SKY) analysis could not only determine the origin and organization of all thus far unidentified structural chromosomal abnormalities but also detect two cryptic unbalanced translocations, which had been erroneously considered to be normal on the basis of G-banding analysis, and correct one abnormality misidentified by G banding. Among these abnormalities, we identified the new partner site of the 14q32 translocation, 22q13, and the jumping translocations involving 2p23 as a new donor chromosome. Furthermore, by using fluorescence in situ hybridization (FISH) with the probes specific for the 14q telomere, we could identify the unbalanced translocation of t(3;14)(q27;q32), which had been erroneously considered to be normal chromosome 3 on the basis of not only G-banding but also of SKY analysis. This translocation is one of the most frequent chromosomal abnormalities in B-cell lymphoma, especially diffuse large cell lymphoma. After SKY and FISH analysis, the original descriptions in the G-band karyotype were modified for a total of 13 chromosomes. The combination of SKY and FISH using the 14q telomere probe was therefore considered very useful for the characterization of complex cytogenetic cases in B-cell lymphoma.

Identification of CRAM, a novel unc-33 gene family protein that associates with CRMP3 and protein-tyrosine kinase(s) in the developing rat brain.

Four members of collapsin response mediator proteins (CRMPs) are thought to be involved in the semaphorin-induced growth cone collapse during neural development. Here we report the identification of a novel CRMP3-associated protein, designated CRAM for CRMP3-associated molecule, that belongs to the unc-33 gene family. The deduced amino acid sequence reveals that the CRAM gene encodes a protein of 563 amino acids, shows 57% identity with dihydropyrimidinase, and shows 50-51% identity with CRMPs. CRAM appears to form a large complex composed of CRMP3 and other unidentified proteins in vivo. Indeed, CRAM physically associates with CRMP3 when co-expressed in COS-7 cells. The expression of CRAM is brain-specific, is high in fetal and neonatal rat brain, and decreases to very low levels in adult brain. Moreover, CRAM expression is up-regulated during neuronal differentiation of embryonal carcinoma P19 and PC12 cells. Finally, immunoprecipitation analysis of rat brain extracts shows that CRAM is co-immunoprecipitated with proteins that contain protein-tyrosine kinase activity. Taken together, our results suggest that CRAM, which interacts with CRMP3 and protein-tyrosine kinase(s), is a new member of an emerging family of molecules that potentially mediate signals involved in the guidance and outgrowth of axons.

Cross-linking of the B cell receptor induces activation of phospholipase D through Syk, Btk and phospholipase C-gamma2.

Phospholipase D (PLD) has been proposed to play a key role in the signal transduction of cellular responses to various extracellular signals. Herein we provide biochemical and genetic evidence that cross-linking of the B cell receptor (BCR) induces rapid activation of PLD through a Syk-, Btk- and phospholipase C (PLC)-gamma2-dependent pathway in DT40 cells. Activation of PLD upon BCR engagement is completely blocked in Syk- or Btk-deficient cells, but unaffected in Lyn-deficient cells. Furthermore, in PLC-gamma2-deficient cells, BCR engagement failed to activate PLD. These results demonstrate that Syk, Btk and PLC-gamma2 are essential for BCR-induced PLD activation.

Requirement of GM2 ganglioside activator for phospholipase D activation.

Sequence analysis of a heat-stable protein necessary for the activation of ADP ribosylation factor-dependent phospholipase D (PLD) reveals that this protein has a structure highly homologous to the previously known GM2 ganglioside activator whose deficiency results in the AB-variant of GM2 gangliosidosis. The heat-stable activator protein indeed has the capacity to enhance enzymatic conversion of GM2 to GM3 ganglioside that is catalyzed by beta-hexosaminidase A. Inversely, GM2 ganglioside activator purified separately from tissues as described earlier [Conzelmann, E. & Sandhoff, K. (1987) Methods Enzymol. 138, 792-815] stimulates ADP ribosylation factor-dependent PLD in a dose-dependent manner. At higher concentrations of ammonium sulfate, the PLD activator protein apparently substitutes for protein kinase C and phosphatidylinositol 4,5-bisphosphate, both of which are known as effective stimulators of the PLD reaction. The mechanism of action of the heat-stable PLD activator protein remains unknown.

Antibodies directed against ZAP-70 cross-react with a 66 kDa tyrosine kinase in the rat brain.

ZAP-70 is another member of Syk family tyrosine kinases which plays an essential role in growth, differentiation, and function of T lymphocytes. In this study, we report the specific expression of a 66 kDa tyrosine kinase that is specifically cross-reacted with anti-ZAP-70 antibodies in the developing neurons. By immunoblot and immunoprecipitation assay using various anti-ZAP-70 antibodies, a 66 kDa tyrosine kinase was detected in lysates from rat brain. During the development of rat brain, expression levels of this 66 kDa tyrosine kinase were highest around 3 weeks after birth and decreased thereafter in the adult. In addition, immunoblot analysis demonstrated that this 66 kDa tyrosine kinase was expressed almost solely in the nervous system. These results suggest that this ZAP-70-related tyrosine kinase may play an important role in growth and differentiation in the developing neurons. Our observations will provide the clue to approach the regulatory system common to neurogenesis and immune response.

Severely decompensated abdominal Wilson disease treated with peritoneal dialysis: a case report.

A 12-year-old girl with severely decompensated abdominal Wilson disease was treated with abdominal dialysis in order to accelerate the excretion of chelated copper. Dialysate without human serum albumin or D-penicillamine was used and was able to accelerate the excretion of chelated copper, with an increment of 5.5-19.7% compared with urinary excretion only.

Purification of a heat-stable activator protein for ADP-ribosylation factor-dependent phospholipase D.

A heat-stable activator for ADP-ribosylation factor (ARF)-dependent phospholipase D (PLD) was purified to near homogeneity from rat kidney cytosol by a sequential column chromatography. The purified activator has a molecular mass of 23 kDa on SDS-PAGE. Using a partially purified ARF-dependent PLD from rat kidney, the activator synergistically stimulates PLD with ARF in time- and dose-dependent manner. In the absence of ARF, the activator has little or no effect. The purified activator also stimulates PLD under several conditions including permeabilized cell system, suggesting that the activator is a physiologically relevant regulator of PLD.

Reconstitution of GTP-gamma-S-dependent phospholipase D activity with ARF, RhoA, and a soluble 36-kDa protein.

For activation of kidney membrane phospholipase D (PLD), cytosol is absolutely needed in addition to GTP-gamma-S. The active component of cytosol consists of three protein factors: ADP-ribosylation factor, RhoA, and a soluble 36-kDa protein. Any combination of these two factors synergistically activates PLD to some extent, but the presence of the three factors causes full activation. The 36-kDa protein is stable at 60 degrees C but inactivated at 80 degrees C for 10 min. Tissue distribution of the 36-kDa protein roughly coincides with that of PLD, suggesting physiological relevance of the protein in the regulation of PLD.