Phase I/II study of combined granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor administration for the mobilization of hematopoietic progenitor cells

PURPOSE: To study the toxicity and efficacy of combined granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) administration for mobilization of hematopoietic progenitor cells (HPCs). MATERIALS AND METHODS: Cohorts of a minimum of five patients each were treated subcutaneously as follows: G-CSF 5 micrograms/kg on days 1 to 12 and GM-CSF at .5, 1, or 5 micrograms/kg on days 7 to 12 (cohorts 1, 2, and 3); GM-CSF 5 micrograms/kg on days 1 to 12 and G-CSF 5 micrograms/kg on days 7 to 12 (cohort 4); and G-CSF and GM-CSF 5 micrograms/kg each on days 1 to 12 (cohort 5). Ten-liter aphereses were performed on days 1 (baseline, pre-CSF), 5, 7, 11, and 13. Colony assays for granulocyte-macrophage colony-forming units (CFU-GM) and erythroid burst-forming units (BFU-E) were performed on each harvest. RESULTS: The principal toxicities were myalgias, bone pain, fever, nausea, and mild thrombocytopenia, but none was dose-limiting. Four days of treatment with either G-CSF or GM-CSF resulted in dramatic and sustained increases in the numbers of CFU-GM per kilogram collected per harvest that represented 35.6 +/- 8.9- and 33.7 +/- 13.0-fold increases over baseline, respectively. This increment was attributable both to increased numbers of mononuclear cells collected per 10-L apheresis and to increased concentrations of progenitors within each collection. The administration of G-CSF to patients already receiving GM-CSF (cohort 4) caused the HPC content to surge to nearly 80-fold the baseline (P = .024); the reverse sequence, ie, the addition of GM-CSF to G-CSF, was less effective. The CFU-GM content of the baseline aphereses correlated with the maximal mobilization achieved (r = .74, P = .001). CONCLUSION: Combined G-CSF and GM-CSF administration effectively and predictably mobilizes HPCs and facilitates apheresis.     

The unique envelope gene of the subgroup J avian leukosis virus derives from ev/J proviruses, a novel family of avian endogenous viruses

A new subgroup of avian leukosis virus (ALV), designated subgroup J, was identified recently. Viruses of this subgroup do not cross-interfere with viruses of the avian A, B, C, D, and E subgroups, are not neutralized by antisera raised against the other virus subgroups, and have a broader host range than the A to E subgroups. Sequence comparisons reveal that while the subgroup J envelope gene includes some regions that are related to those found in env genes of the A to E subgroups, the majority of the subgroup J gene is composed of sequences either that are more similar to those of a member (E51) of the ancient endogenous avian virus (EAV) family of proviruses or that appear unique to subgroup J viruses. These data led to the suggestion that the ALV-J env gene might have arisen by multiple recombination events between one or more endogenous and exogenous viruses. We initiated studies to investigate the origin of the subgroup J envelope gene and in particular to determine the identity of endogenous sequences that may have contributed to its generation. Here we report the identification of a novel family of avian endogenous viruses that include env coding sequences that are over 95% identical to both the gp85 and gp37 coding regions of subgroup J viruses. We call these viruses the ev/J family. We also report the isolation of ev/J-encoded cDNAs, indicating that at least some members of this family are expressed. These data support the hypothesis that the subgroup J envelope gene was acquired by recombination with expressed endogenous sequences and are consistent with acquisition of this gene by only one recombination event.     

Aliphatic and alicyclic diols induce melanogenesis in cultured cells and guinea pig skin

The forces and moments in the shaft of a distal femoral replacement were measured by telemetry for a subject during different activities, and calculations were then made of the forces at the knee. The axial force showed a small peak at heel-strike followed by two main peaks during stance. In level walking, the peak axial force was between 1,487 and 1,718 N (2.2-2.5 BW), the peak shear force was 269-368 N (0.4-0.54 BW) directed anteriorly on the tibia, the peak axial torque was 7 Nm internal, while the patellofemoral force was 466-571 N. The highest axial force was recorded for descending stairs (2.8 BW). Standing on one leg produced 2.4 BW, while lying supine and raising the leg produced 1.7 BW. The data produced may resemble that of a normal subject, and has application to basic joint mechanics, to joint reconstruction, and to total knee replacement design and evaluation.     

Monitoring the role of aceticlasts in anaerobic digestion: activity and capacity

Aceticlastic methanogens are seen as a key to digester capacity and stability. This paper develops and applies an assay to measure digester stability by measuring the maximum aceticlastic methane production rate (V_max,ac). The V_max,ac in combination with acetate concentrations was found to be an effective digestion monitoring tool to indicate process upsets. At steady state, thermophilic, first stage and short SRT digesters generally had a greater V_max,ac than mesophilic, second stage or long SRT digesters. The ratio of the V_max,ac to the plant aceticlastic methane production rate, termed the Acetate Capacity Number (ACN), is a measure of the excess capacity of the digester. Either V_max,ac or ACN can be used to estimate the capability to handle higher organic loading rates. Monod modeling was used to predict V_max,ac, ACN and maximum VS loading rates for mesophilic and thermophilic digestion and for staged digesters to better understand expected digestion capacity and stability.     

A highly efficient six-stroke internal combustion engine cycle with water injection for in-cylinder exhaust heat recovery

A concept adding two strokes to the Otto or Diesel engine cycle to increase fuel efficiency is presented here. It can be thought of as a four-stroke Otto or Diesel cycle followed by a two-stroke heat recovery steam cycle. A partial exhaust event coupled with water injection adds an additional power stroke. Waste heat from two sources is effectively converted into usable work: engine coolant and exhaust gas. An ideal thermodynamics model of the exhaust gas compression, water injection and expansion was used to investigate this modification. By changing the exhaust valve closing timing during the exhaust stroke, the optimum amount of exhaust can be recompressed, maximizing the net mean effective pressure of the steam expansion stroke (MEP_steam). The valve closing timing for maximum MEP_steam is limited by either 1 bar or the dew point temperature of the expansion gas/moisture mixture when the exhaust valve opens. The range of MEP_steam calculated for the geometry of a conventional gasoline engine and is from 0.75 to 2.5 bars. Typical combustion mean effective pressures (MEP_combustion) of naturally aspirated gasoline engines are up to 10 bar, thus this concept has the potential to significantly increase the engine efficiency and fuel economy.     

Estimating Stream Temperature from Air Temperature: Implications for Future Water Quality

This study examines the air temperature/stream temperature relationship at a geographically diverse set of streams. We evaluate the general temperature relationships (both linear and nonlinear) that apply to these streams, and then examine how changes in stream temperature associated with climate variability or climate warming might affect dissolved oxygen levels. The majority of streams showed an increase in water temperature of about 0.6–0.8°C for every 1°C increase in air temperature, with very few streams displaying a linear 1:1 air/water temperature trend. For most of the streams, a nonlinear model produced a better fit than did a simple linear model. Understanding the relationship between air temperature and water temperature is important if people want to estimate how stream temperatures are likely to respond to anticipated future increases in surface air temperature. Surface water temperature in many streams will likely increase 2 to 3°C as air temperature increases 3 to 5°C. At sites with currently low dissolved oxygen content, an increase in summer stream temperatures could cause the dissolved oxygen levels to fall into a critically low range, threatening the health of many aquatic species.     

A Comparison of Anticonvulsants in the Treatment of Impulsive Aggression.

This study compared the behavioral effects of 3 anticonvulsants in impulsive aggressive men. In a double-blind, placebo-controlled, parallel groups design, participants were randomly assigned to 1 of 4 6-week treatments: phenytoin (n = 7), carbamazepine (n = 7), valproate (n = 7), or placebo (n = 8). The efficacy measure was the average aggression score, a global severity index from the Overt Aggression Scale (J. M. Silver & S. C. Yudofsky, 1991). Analysis showed a significant reduction in impulsive aggression during all 3 anticonvulsant conditions compared with placebo. However, the treatment effect during carbamazepine administration was slightly delayed compared with phenytoin and valproate. These findings suggest that increased use of anticonvulsants could make a significant impact in the control of impulsive aggression in both mental health and criminal justice settings. (PsycINFO Database Record (c) 2010 APA, all rights reserved)