Predictors of GBV-C infection among patients referred for renal transplantation

The etiology of liver disease remains unknown in about 4 to 23% of dialysis patients and 10 to 16% of renal transplant recipients. A search for other causative agents of liver disease led to the discovery of the GB group of viruses. We studied the association between the presence of GB virus C (GBV-C) infection, known risk factors for parenterally-transmitted infections and history or laboratory evidence of liver disease among end-stage renal disease (ESRD) patients referred for renal transplantation to the New England Organ Bank, MA. Stored sera from patients on the renal transplantation waiting list between November 1986 and June 1990 were tested for antibody to hepatitis C virus (HCV). Sera were available in 1544 of 3243 (48%) patients, and anti-HCV was detected by ELISA3 in 287 (19%). All 287 anti-HCV positive patients formed the anti-HCV positive cohort and 286 randomly selected anti-HCV negative patients formed the anti-HCV negative cohort (573 patients overall). Additional sera were available for GBV-C RNA testing in 465 of 573 (81%) patients, and GBV-C RNA was detected by RT-PCR in 146. The overall extrapolated prevalence of serum GBV-C RNA was 29%. The prevalence of serum GBV-C RNa among anti-HCV positive patients (35%) was not significantly different from that among anti-HCV negative patients (29%; P = 0.22). In a univariate analysis, compared to patients without GBV-C RNA, patients with serum GBV-C RNA were younger [odds ratio (OR) 0.98 per year of age, P = 0.01], had a lower proportion of males (OR 0.64, P = 0.03), lower proportion of patients with diabetes mellitus (OR 0.44, P = 0.01), higher proportion of patients with a previous transplantation (OR 1.53, P = 0.04), longer duration of dialysis at the time of enrollment (OR 1.004 per month on dialysis, P = 0.03), and a higher proportion of patients with history of transfusions (OR 4.58, P = 0.01). Serum GBV-C RNA was not associated with a significantly increased OR for history of liver disease or non-A, non-B hepatitis, or elevated serum alanine aminotransferase levels. In a step-wise multivariate regression analysis, a younger age (OR 0.98 per year of age, P = 0.03), and history of blood transfusions (OR 3.89, P = 0.03) were associated with an increased OR for serum GBV-C RNA, while diabetes mellitus was associated with a decreased OR for GBV-C RNA (OR 0.47, P = 0.01). Anti-HCV was not a predictor of serum GBV-C RNA (OR 1.07, P = 0.77). The results of this study support the fact that GBV-C is a parenterally transmitted virus and shed light on the modes of transmission of GBV-C among ESRD patients. However, the association with liver disease remains to be established.     

Effects of the Na+/H+-exchange inhibitor Hoe 642 on intracellular pH, calcium and sodium in isolated rat ventricular myocytes

The inhibitors of the Na+/H+-exchange (NHE1) system Hoe 694 and Hoe 642 possess cardioprotective effects in ischaemia/reperfusion. It is assumed that these effects are due to the prevention of intracellular sodium (Nai) and calcium (Cai) overload. The purpose of the present study was to investigate the effects of Hoe 642 on intracellular pH, Na+ and Ca2+ (pHi, Nai and Cai) in isolated rat ventricular myocytes under anoxic conditions or in cells in which oxidative phosphorylation had been inhibited by 1.5 mmol/l cyanide. In cells which were dually loaded with the fluorescent dyes 2, 7-biscarboxyethyl-5,6-carboxyfluorescein (BCECF) and Fura-2, anoxia caused acidification of the cells (from pHi 7.2 to pHi 6.8) and an increase in Cai from about 50 nmol/l to about 1 micromol/l. The decrease in pHi began before the cells underwent hypoxic (rigor) contracture, whereas Cai only began to rise after rigor shortening had taken place. After reoxygenation, pHi returned to its control value and Cai oscillated and then declined to resting levels. It was during this phase that the cells rounded up (hypercontracture). When 10 micromol/l Hoe 642 was present from the beginning of the experiment, pHi and Cai were not significantly different from control experiments. At reoxygenation, pHi did not recover, but Cai oscillated and returned to its resting level. To monitor Nai, the cells were loaded with the dye SBFI. After adding 1.5 mmol/l cyanide or 100 micromol/l ouabain, Nai increased from the initial 8 mmol/l to approximately 16 mmol/l. Hoe 642 or Hoe 694 (10 micromol/l) did not prevent the increase in Nai. In contrast, the blocker of the persistent Na+ current R56865 (10 micromol/l) attenuated the CN--induced rise in Nai. The substance ethylisopropylamiloride was not used because it augmented considerably the intensity of the 380 nm wavelength of the cell's autofluorescence. In conclusion, the specific NHE1 inhibitor Hoe 642 did not attenuate anoxia-induced Cai overload, nor CN--induced Nai and Cai overload. Hoe 642 prevented the recovery of pHi from anoxic acidification. This low pHi maintained after reoxygenation may be cardioprotective. Other possible mechanisms of NHE1 inhibitors, such as prevention of Ca2+ overload in mitochondria, cannot be ruled out. The increase in Nai during anoxia is possibly due to an influx of Na+ via persistent Na+ channels.     

Treatment with the oral growth hormone secretagogue MK-677 increases markers of bone formation and bone resorption in obese young males

The effect of 2 months of treatment with the oral growth hormone (GH) secretagogue MK-677 on markers of bone metabolism was determined in healthy obese male subjects. This was a randomized, double-blind, parallel, placebo-controlled study. Twenty-four healthy obese males, 19-49 years of age, with body mass index > 30 kg/m2 were treated with MK-677 (25 mg/day; n = 12) or placebo (n = 12) for 8 weeks. MK-677 increased markers of bone formation; a 23% increase in the carboxy-terminal propeptide of type I procollagen levels and a 28% increase in procollagen III peptide levels were seen with as little as 2 weeks of MK-677 treatment (p < 0.01 and p = 0.001 vs. placebo, respectively) while a 15% increase in serum levels of osteocalcin was not detected until 8 weeks of treatment (p < 0.01 vs. placebo). Markers of bone resorption were induced within 2 weeks of treatment with MK-677; serum levels of the carboxy-terminal cross-linked telopeptide of type I collagen were increased 26% at 8 weeks (p = 0.001 vs. placebo), and urine hydroxyproline/creatinine and calcium/creatinine ratios at 8 weeks were increased by 23% (p < 0.05 vs. placebo) and 46% (p < 0.05 vs placebo), respectively, MK-677 increased serum insulin-like growth factor binding protein-5 (IGFBP-5) by 43-44% after 2-8 weeks of treatment (p < 0.01 vs. placebo). Serum IGFBP-4 was increased by 25% after 2 weeks of treatment (p < 0.001 vs. placebo) but no significant change from baseline was observed after 8 weeks of treatment. Plasma interleukin-6 was not significantly changed by active treatment. In conclusion, short-term treatment of healthy obese male volunteers with the GH secretagogue MK-677 increases markers of both bone resorption and formation. Large increases in serum levels of IGF-1 and IGFBP-5 and a transient increase in serum IGFBP-4 were found. Future long-term studies are needed to investigate if prolonged treatment with MK-677 increases bone mass.     

Constrained length minimum inductance gradient coil design

A gradient coil design algorithm capable of controlling the position of the homogeneous region of interest (ROI) with respect to the current-carrying wires is required for many advanced imaging and spectroscopy applications. A modified minimum inductance target field method that allows the placement of a set of constraints on the final current density is presented. This constrained current minimum inductance method is derived in the context of previous target field methods. Complete details are shown and all equations required for implementation of the algorithm are given. The method has been implemented on computer and applied to the design of both a 1:1 aspect ratio (length:diameter) central ROI and a 2:1 aspect ratio edge ROI gradient coil. The 1:1 design demonstrates that a general analytic method can be used to easily obtain very short gradient coil designs for use with specialized magnet systems. The edge gradient design demonstrates that designs that allow imaging of the neck region with a head sized gradient coil can be obtained, as well as other applications requiring edge-of-cylinder regions of uniformity.     

E1A second exon requirements for induction of target cell susceptibility to lysis by natural killer cells: implications for the mechanism of action

Recombinant human granulocyte colony-stimulating factor (G-CSF) at a dose of 1 to 300 micrograms/kg/day was administered intravenously to rats daily for 13 weeks. Serum alkaline phosphatase (ALP) activity increased dose-dependently with leukocytosis. Most of the increased leukocytes were segmented neutrophils, and neutrophil alkaline phosphatase (NAP) scores were elevated markedly. Serum ALP activity correlated very well with the segmented neutrophil counts, and the coefficient of correlation was more than 0.97 in both sexes. Pathological examinations revealed splenomegaly and a marked increase in neutrophils in the red pulp of the spleen. In the spleen, phagocytosis of neutrophils by macrophages was observed. These data indicate that the increased ALP was of neutrophil origin. Serum ALP activity may be increased by the direct release of ALP from the high number of neutrophils into the blood, or by the leakage of ALP into the blood mainly from the spleen where many neutrophils are pooled and destroyed by the macrophage system.     

Seasonal variation in light penetration and subsurface chlorophyll-α in southern Lake Michigan observed by a glider

The Cooperative Institute for Great Lakes Research (CIGLR) in collaboration with the Great Lakes Observing System and National Oceanic and Atmospheric Administration, Great Lakes Environmental Research Laboratory (NOAA GLERL) deployed an autonomous underwater glider in southern Lake Michigan several times per year between 2012 and 2019 to collect offshore (>30 m depth) limnological measurements, including temperature, photosynthetically active radiation (beginning during 2015), and chlorophyll-α fluorescence. From these data, we calculated mixed layer depth, several measures of light penetration (diffuse attenuation coefficient, first optical depth, euphotic zone depth), and depth of the subsurface chlorophyll-α maxima. During summer, mean offshore mixed layer depth was typically 10–15 m, K_d for PAR was 0.1–0.17 m^?1, first optical depth was 6–9 m, euphotic zone depth was 35–40 m, and depth of subsurface chlorophyll-α maxima was 30–35 m. We also observed substantial spatial and temporal variation in these values across the basin and within and among seasons. Glider-based observations provide a wider horizontal and vertical perspective than other methods (e.g., ship- and satellite-based observations, buoys, and fixed moorings), and are therefore a valuable, complementary tool for Great Lakes limnology. The set of observations reported here provide seasonal and basin-scale information that may help to identify anomalies useful for future glider-assisted investigation into the role of biophysical processes in Great Lakes limnology and ecology.     

Effect of a direct magnetic field on the interfacial microstructure between molten aluminium and solid iron

Many processing techniques, such as hot dip aluminizing, bimetal formation, liquid metal corrosion, cementing, welding and diffusion bonding, are basically dependent on interfacial reactions [1-3]. It is therefore important to investigate the formation and growth of intermetallic layers at the interface. There have been several studies carried out to examine chemical compositions and growth kinetics of intermetallic layers in the Al-Fe system [4-9]. Most authors have come to an agreement that…     

Enhanced Fracture Toughness in Layered Microcomposites of Ce-ZrO2 and Al2O3

Laminar composites, containing layers of Ce-ZrO₂ and either Al₂O₃ or a mixture of Al₂O₃ and Ce-ZrO₂, have been fabricated using a colloidal method that allowed formation of layers with thicknesses as small as 10 μm. Strong interactions between these layers and the martensitic transformation zones surrounding cracks and indentations have been observed. In both cases, the transformation zones spread along the region adjacent to the layer, resulting in an increased fracture toughness. The enhanced fracture toughness was observed for cracks growing parallel to the layers as well as for those that were oriented normal to the layers.     

High-Strength Zirconia Fibers

Fine-grained polycrystalline zirconia fibers have been formed from an acetate precursor. The fibers contained a Y₂O₃ additive, which inhibited grain growth (grain size ≤0.5 μm) and allowed the tetragonal phase to be retained at room temperature. Fibers with diameters in the range 2 to 5 μm had strengths in the range 1.5 to 2.6 GPa.     

Direct Measurement of Transformation Zone Strains in Toughened Zirconia

Residual strains responsible for crack tip shielding have been measured within transformation zones surrounding cracks in Mg-PSZ. Two techniques were used for strain measurement: moiré interferometry and high-resolution image matching. Both methods provide maps of differential in-plane displacements within the specimen surface intersected by the crack, the latter method with the higher resolution. The results are compared with finite-element analysis to assess surface relaxation effects, and the measured strains are used to evaluate the crack tip shielding stress intensity factor. Calculations based on the assumption that the unconstrained transformation strain is hydrostatic dilatation yielded results that were significantly smaller than the measured toughness increases.