Loss of Endoreduplication as Morphogenesis of Micromegakaryocytes in Myelodysplastic Syndrome.

Morphogenesis of micromegakaryocytes in MDS was investigated in a case of refractory anemia with excess of blasts by analysing megakaryocyte colonies developed from peripheral blood mononuclear cells in a semi-solid culture containing aplastic anemia patient\u27s plasma as source for megakaryocyte colony stimulating factor and thrombopoiesis stimulationg factor. Candidate megakaryocyte colonies were individually stained for glycoprotein (GP)IIb/IIIa by immunocytochemical method. Three types of colonies were distinguished ; type I composed of 10-30 large magakaryocytes with high ploidy number, type II composed of 50-200 micromegakaryocytes with single nucleus, and type III composed of 20-50 micromegakaryocytes. Type I colonies were similar to megakaryocyte colonies obtained from three control subjects. Periodic in situ observation of type II and III colonies disclosed that large megakaryocytes never appeared during 21 days\u27 culture, suggesting mitotic growth at every generation. These findings indicate that loss of endoreduplication is primary defect in micromegakaryocyte formation by MDS clone. Quantitaive aspect of platelet formation by micromegakaryocytes could not be assessed in this study, but morphological observation in situ or on GPIIb/IIIa-stained preparation suggested reduced platelet production. Biological significance of diminished endoreduplication is yet to be determined in respect to leukemic predisposition

In Vitro Study of the Independent and Combined Effects of Recombinant Human GM-CSF and G-CSF on Normal Bone Marrow Granulocytes : GM-CSF Enhances the Growth Effect but Suppresses the Terminal Maturation-inducing Effect of G-CSF

We studied the independent and combined effects of recombinant human granulocyte colony- stimularting factor (rhG-CSF) and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on the growth and maturation of neutrophilic granulocytes. Absolute granulocyte numbers, cellular composition, and neutrophil alkailne phosphatase (NAP) activity were examined after normal nonphagocytic bone marrow cells were cultured for seven days with rhG-CSF, rhGM-CSF, and a combination of both growth factors. The numbers of band and segmented forms produced in the cultures containing rhGM-CSF were significantly lower than in control cultures or those with rhG-CSF. When both rhGM-CSF and rhG-CSF were in the culture total granulocyte production was highest, but the increment of band and segmented forms produced by rhG-CSF alone was reduced. Neutrophil alkaline phosphatase (NAP), an enzyme marking terminal maturation, was increased by rhG-CSF alone, but not by rhGM-CSF alone. Cultures containing both CSFs showed significantly lowered NAP activity compared to those containing rhG-CSF alone. The decrement in NAP activity was proportionate to the amount of rhGM-CSF added. These results indicate that terminal maturation-inducing effect is a property of rhG-CSF but not of rhGM-CSF. In the presence of both GM-CSF and G-CSF, the growth of granulocytes is maximumly stimulated but the terminal maturation-inducing effect of rhG-CSF is suppressed

Oligomerization of Hepatitis C Virus Core Protein is Crucial for Interaction with the Cytoplasmic Domain of E1 Envelope Protein

Hepatitis C virus (HCV) contains two membrane-associated envelope glycoproteins, E1 and E2, which assemble as a heterodimer in the endoplasmic reticulum (ER). In this study, predictive algorithms and genetic analyses of deletion mutants and glycosylation site variants of the E1 glycoprotein were used to suggest that the glycoprotein can adopt two topologies in the ER membrane: the conventional type I membrane topology and a polytopic topology in which the protein spans the ER membrane twice with an intervening cytoplasmic loop (amino acid residues 288 to 360). We also demonstrate that the E1 glycoprotein is able to associate with the HCV core protein, but only upon oligomerization of the core protein in the presence of tRNA to form capsid-like structures. Yeast two-hybrid and immunoprecipitation analyses reveal that oligomerization of the core protein is promoted by amino acid residues 72 to 91 in the core. Furthermore, the association between the E1 glycoprotein and the assembled core can be recapitulated using a fusion protein containing the putative cytoplasmic loop of the E1 glycoprotein. This fusion protein is also able to compete with the intact E1 glycoprotein for binding to the core. Mutagenesis of the cytoplasmic loop of E1 was used to define a region of four amino acids (residues 312 to 315) that is important for interaction with the assembled HCV core. Taken together, our studies suggest that interaction between the self-oligomerized HCV core and the E1 glycoprotein is mediated through the cytoplasmic loop present in a polytopic form of the E1 glycoprotein

Association between asymptomatic hyperuricemia and new-onset chronic kidney disease in Japanese male workers: a long-term retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>Hyperuricemia is prevalent in patients with chronic kidney disease (CKD). We explored the hypothesis that asymptmatic hyperuricemia may be associated with new-onset CKD.</p> <p>Methods</p> <p>The participants were all male factory workers in Kanagawa, Japan (n = 1,285). All were over 40 years of age and had undergone annual health examinations from 1990 to 2007. Individuals with a history of gouty attacks were excluded from the study. A retrospective cohort study was conducted by following the estimated glomerular filtration rate (eGFR) for each participant over a maximum period of 18 years. The endpoint was new-onset CKD defined as eGFR < 60 mL/min/1.73 m². The associations between new-onset CKD and the presence of hyperuricemia, low serum high-density lipoprotein cholesterol, hypertension, diabetes, and obesity were analyzed.</p> <p>Results</p> <p>The mean (± standard deviation) follow-up period was 95.2 (± 66.7) months, and new-onset CKD was observed in 100 participants (7.8%) during this follow-up. Cox proportional hazards model revealed that the hazard ratio of new-onset CKD due to hyperuricemia, low serum high-density lipoprotein cholesterol, hypertension and obesity were 3.99 (95% confidence interval: 2.59-6.15), 1.69 (1.00-2.86), 2.00 (1.29-3.11) and 1.35 (0.87-2.10), respectively. Concerning hyperuricemia, low serum high-density lipoprotein cholesterol, hypertension and obesity, the log-rank tests showed <it>P </it>values of < 0.01, 0.01, < 0.01 and < 0.01, respectively.</p> <p>Conclusion</p> <p>The results of this study suggest that asymptomatic hyperuricemia is a predictive factor for new-onset CKD for Japanese male workers.</p

Reservoir purification by using micro-bubble aerator

Proceedings of the Seventh International Conference on Hydroscience and Engineering, Philadelphia, PA, September 2006. http://hdl.handle.net/1860/732A new hypolimnetic aeration system was devised and its performance of water purification was examined in in-situ experiments. The system feeds fine micro-bubbles to the anoxic hypolimnion. Two types of aeration were conducted; the first one was aeration with natural air and the second one was oxygen aeration. It was confirmed in both of the experiments that the hypolimnion was kept aerobic even during midsummer, while it used to be kept completely anoxic in the absence of aeration. Since the oxygen micro-bubbles show higher solubility than the air micro-bubbles, dissolved oxygen in the hypolimnion was greatly recovered and even over-saturated in the case of oxygen aeration. In both cases, the micro-bubble aeration scarcely agitated the water, thus causing the thermal stratification to be well-preserved without generating predominant vertical mixing. Although the reservoir had suffered from serious oxygen depletion and contamination in the hypolimnion before the aeration, concentrations of nutrients, manganese and iron significantly decreased after starting the hypolimnetic aeration. The two reservoirs are now almost free from hypolimnetic contamination

Impact Analysis of Carbon Tax on the Renewal Planning of Energy Supply System for an Office Building

An optimal planning method is proposed for the renewal planning problem of an energy supply system installed into building from economic viewpoint. In this method, the objective function to be minimized is the average annual total cost during the evaluation period of the objective system based on the annualized costs method, and the renewal year is considered as a decision variable together with the renewal system’s structure, equipment capacities, and system’s operational strategy. This problem is formulated as one of the mixed integer linear programming problem, and a numerical study is carried out for an office building with the total floor area of 15 000m2 by using the GAMS/CPLEX solver. Impact analysis of the carbon tax introduction is mainly studied on the renewal planning mentioned above, and the following results are obtained: a) The optimal renewal strategy is not affected by the future carbon tax introduction at the standard rate such as 655 Japanese yen/t-CO2 argued presently in Japan. b) By increasing the above tax rate more than 13 times higher, structure of the optimal renewal system changes suddenly, and equipment with high energy conversion efficiency becomes to be installed in spite of its expensive initial cost

Up to 6-year follow-up after pulmonary vein isolation for persistent/permanent atrial fibrillation: Importance of sinus node function

ObjectiveSinus node dysfunction is commonly associated with atrial fibrillation. There is little information about the long-term results of pulmonary vein isolation in relation to sinus node function. The present study was conducted to investigate whether sinus node dysfunction affects the late outcome of pulmonary vein isolation in patients with persistent/permanent atrial fibrillation.MethodsAmong 76 consecutive patients with persistent/permanent atrial fibrillation who had undergone cut-and-sew pulmonary vein isolation, 66 patients without evidence of intra-atrial thrombus by transesophageal echography, and who were able to tolerate cardioversion, were enrolled. Sinus node recovery time after cardioversion was examined intraoperatively. All of the patients underwent valvular surgery concomitantly (mitral in 62).ResultsSinus node dysfunction was detected in 18 patients. These patients had a significantly lower f wave voltage in V1 of the electrocardiogram and a larger cardiothoracic ratio than patients with normal sinus node function. Hospital mortality was 3%, and 3 late deaths were observed. Follow-up was conducted for up to 72 months (mean 30 months), with a 100% complete follow-up rate. There were no significant differences in actuarial survival and freedom from cardiac events between patients with normal and abnormal sinus node function. No thromboembolic events occurred. A significantly higher proportion of patients with normal sinus node function (82%) were free of atrial fibrillation at 4 years than patients with sinus node dysfunction (25%; P < .0001).ConclusionsThe atrial fibrillation cure rate after pulmonary vein isolation may be influenced by sinus node function in both the early and late stages. Although further examinations are required, pulmonary vein isolation may be an adequate treatment for persistent/permanent atrial fibrillation in patients with normal sinus node function