A new methodology for hydrodynamic similarity in bubble columns

A new hypothesis has been proposed in this work for hydrodynamic similarity that can be subsequently used for scale‐up of bubble column reactors. The proposed hypothesis takes into account both global (by matching overall gas holdup) as well as local hydrodynamics (by matching time‐averaged radial profile/cross‐sectional distribution of gas holdup) to maintain similarity in two systems. The evaluation of proposed hypothesis has been accomplished utilising advanced diagnostic techniques such as gamma‐ray computed tomography (CT) and computer automated radioactive particle tracking (CARPT). In this work, we experimentally demonstrate that similarity based only on global hydrodynamics does not necessarily ensure similar mixing and turbulence in two systems. It is essential to maintain similar global as well as local hydrodynamics. The hydrodynamic similarity that can be obtained by matching the commonly used dimensionless groups was also evaluated at these experimental conditions.     

Interaction of the p53-regulated protein Gadd45 with proliferating cell nuclear antigen

GADD45 is a ubiquitously expressed mammalian gene that is induced by DNA damage and certain other stresses. Like another p53-regulated gene, p21WAF1/CIP1, whose product binds to cyclin-dependent kinases (Cdk's) and proliferating cell nuclear antigen (PCNA), GADD45 has been associated with growth suppression. Gadd45 was found to bind to PCNA, a normal component of Cdk complexes and a protein involved in DNA replication and repair. Gadd45 stimulated DNA excision repair in vitro and inhibited entry of cells into S phase. These results establish GADD45 as a link between the p53-dependent cell cycle checkpoint and DNA repair.     

Analysis of the thrombin inhibitor DuP 714 by an enzyme-linked immunosorbent assay

Resident proteins of the exocytic pathway contain at least two types of information in their primary sequence for determining their subcellular location. The first type of information is found at the carboxyl terminus of soluble proteins of the endoplasmic reticulum (ER) and in the cytoplasmic domain of some ER and Golgi membrane proteins. It acts as a retrieval signal, returning proteins that have left the compartment in which they reside. The second type of information has been found in the membrane-spanning domain of several ER and Golgi proteins and, though the mechanism by which it operates is still unclear, it acts as a retention signal, keeping the protein at a particular location within the organelle. The presence of both a retrieval signal and a retention signal in a trans-Golgi network resident protein suggests that more than one mechanism operates to ensure correct localization of resident proteins along the exocytic pathway.     

Variants of fractionation of irradiation in intracavitary gamma-therapy

Under study was the efficacy of three schedules of dose fractionation in intracavitary gamma-therapy in cervical cancer patients treated on the machine "AGAT-B". Single doses were 1000, 700 and 500 rad, while total dosage at point A depending on the stage of the disease was within the range of 4000-5000 rad. The survival during the first, second and third years following termination of the radiotherapy was found to be identical for patients of all the groups under examination. No differences were noted in them also in the character of early radiation reactions on the part of the adjacent organs. The frequency and severity of late radiation injuries of the urinary bladder, rectum and vagina were related to the dose fractionation regimen.     

Actinomycin D binding to single-stranded DNA: sequence specificity and hemi-intercalation model from fluorescence and 1H NMR spectroscopy

Various in vitro studies have shown that delta-9-tetrahydrocannabinol (THC), the major psychoactive component of marijuana, has a variety of inhibitory effects on immune functions including effects on macrophages. The present studies have examined the mechanism of THC's effects on tumor necrosis factor alpha (TNF-alpha), a major macrophage-produced cytokine and an important mediator involved in cytokine networks and in host defense mechanisms. Exposure of macrophages to medium containing THC has resulted in low levels of soluble TNF-alpha protein and reduced TNF-alpha bioactivity in the culture supernatant. However, THC did not inhibit the levels of LPS-induced TNF-alpha mRNA and intracellular TNF-alpha precursor protein, had only a weak effect on expression of membrane-bound TNF-alpha, but suppressed TNF-alpha maturation/secretion by macrophages. The higher the THC concentration in the medium during TNF-alpha induction, the greater the amount of intracellular TNF-alpha precursors that accumulated in the activated macrophages and the less mature TNF-alpha was released from the cells. Data suggest that TNF-alpha production by macrophages was altered greatly by exposure to THC at the levels of TNF-alpha precursor maturation and secretion.     

Reduction of renal uptake of monoclonal antibody fragments by amino acid infusion

The renal uptake of radiolabeled antibody fragments and peptides presents a problem in radioimmunodetection and therapy, compromising lesion sensitivity, especially with intracellularly-retained isotopes. Previously, we showed that cationic amino acids and their derivatives are capable of significantly reducing kidney uptake in animals. We report our initial clinical results of successful renal uptake reduction in five patients who underwent cancer radioimmunodetection with 99mTc-anti-CEA Fab' fragments. METHODS: The patients were infused with two liters of a commercially-available nutritive amino acid solution (containing approximately 2.25 g/liter lysine-glutamate and 2.50 g/liter arginine), whereas 75 control patients received the same volume of saline (quantification of organ and tumor kinetics from conjugate whole-body views by ROI technique). RESULTS: The renal uptake in the amino acid group was significantly lower (p<0.05) than in the control group (11.1 +/- 2.0% injected dose versus 17.7 +/- 7.0% injected dose at 24 hr postinjection), whereas the uptake of all other organs remained unaffected. Gel filtration chromatography of the urine taken from amino-acid-treated patients showed that a significantly higher amount of excreted activity was bound to intact Fab' (53% of excreted activity) in contrast to only less than 10% in the control group. CONCLUSION: The renal uptake of monoclonal antibody fragments in patients can be reduced significantly by amino acid infusion, even at considerably lower doses than those that were safe and effective in animals. As was found in animals, the mechanism seems to rely on an inhibition of the re-absorption of tubularly-filtered proteins by the proximal tubule cells. These results encourage further clinical trials to lower the renal uptake experienced in radioimmunodetection, as well as in therapeutic trials with antibody fragments and peptides.     

The lipid-lowering effects of atorvastatin, a new HMG-CoA reductase inhibitor: results of a randomized, double-masked study

This randomized, placebo-controlled, double-masked, parallel-group trial assessed the serum cholesterol-lowering effects of atorvastatin, a new 3-hydroxy-3-methylglutaryl coenzyme. A reductase inhibitor, over 26 weeks in patients with primary hypercholesterolemia. Thirty-nine patients from four centers in the United States were originally randomized to one of two treatment groups and received either atorvastatin 10 mg (20 patients) or placebo (19 patients) once daily. Atorvastatin rapidly and significantly reduced serum total cholesterol, low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B levels. LDL-C was reduced 35% with atorvastatin 10 mg compared with a 0% increase in LDL-C in the placebo group. Atorvastatin significantly reduced triglyceride levels, with improvements occurring over time. At 26 weeks, triglyceride levels were reduced by 21% with atorvastatin treatment compared with a 14% increase with placebo. The drug was well tolerated and no clinically significant laboratory abnormalities were detected.