Results of transplantation for acute and chronic hepatic allograft rejection

B-chronic lymphocytic leukemia (CLL) is characterized by an accumulation of long-lived, resting B cells expressing the Bcl-2 protein. However, less than 10% of the CLL patients shows bcl-2 gene rearrangement in blood cells, using traditional Southern blotting analysis. In the present study, rearrangement of the bcl-2 gene in CLL cells was studied by pulsed-field gel electrophoresis (PFGE). With this method, large DNA fragments (> 50-10,000 kb) could be analyzed. Blood CLL cells from 9 of 9 patients and 2 of 2 CLL cell lines showed rearranged bcl-2 gene. In comparison, healthy blood B cells and lymphoblastoid cell lines (LCLs) established from normal peripheral blood lymphocytes of the patients showed only germ line configuration. Thus, the possibility of restriction fragment length polymorphisms (RFLPs) in this gene could be excluded. The primary cell involved in CLL might be a progenitor B cell that has accidentally rearranged the bcl-2 gene. As a consequence, such cells express stable amount of Bcl-2 protein and do not enter apoptosis. During prolonged survival, such cells may acquire secondary changes including chromosomal translocations and mutations.     

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.     

Pyrazoline bisphosphonate esters as novel antiinflammatory and antiarthritic agents

Vinylidenebisphosphonic acid tetraethyl ester (1) and diazo ketones 7a-1 in ether at 22 degrees C yield pyrazoline bisphosphonate tetraethyl esters 8a-1 in moderate to good yield. These compounds were evaluated in animal models of arthritis: rat adjuvant-induced polyarthritis (AIP) and murine antigen-induced arthritis (AIA) and a murine model of chronic inflammation, the delayed type hypersensitivity granuloma reaction (DTH-GRA). (5-Benzoyl-2,4-dihydro-3H-pyrazol-3-ylidene)-bisphosphonic acid tetraethyl ester (8a), and [5-(3-fluorobenzoyl)-2,4-dihydro-3H-pyraxol-3-ylidene]- bisphosphonic acid tetraethyl ester (8d) significantly inhibited the arthritis models, AIP (15 mg/kg) and AIA (25 mg/kg), as well as the DTH-GRA (25 mg/kg). Conversion of 8a to the corresponding bisphosphonic acid, 10a, resulted in loss of activity. Compounds with alkyl substituents on the pyrazoline nitrogen, 9a-d, were inactive in the DTH-GRA. These results show that 8a and 8d have novel antiinflammatory activity and are capable of inhibiting chronic arthritis and inflammation in animals. Such compounds might be useful in man for treating chronic tissue injury associated with arthropathies such as inflammatory joint disease as well as other chronic inflammatory diseases.     

Anticonvulsant and antibiotic prophylaxis in head injury

The evidence for and against the prophylactic use of anticonvulsants and antibiotics in head injury is reviewed. There is a lack of blinded placebo-controlled trials in this area. On balance there is no compelling evidence to support the use of either anticonvulsant or antibiotic prophylaxis in head injury, with the possible exception of antibiotic prophylaxis in compound depressed skull fractures and penetrating brain injuries.     

Fast divalent ion conduction in Ba++, Cd++ and Sr++ beta″ aluminas

Single crystals of Ba⁺⁺, Cd⁺⁺ and Sr⁺⁺ beta″ alumina were prepared from sodium beta″ alumina by ion exchange. The conductivities of these divalent ion solid electrolytes exceed 10^?3 (ohm-cm)^?1 at 300°C. These compounds appear to exhibit fast divalent ion motion at moderate temperatures.     

Direct calculation of the sulphur electrode resistance in sodium-sulphur cells

A simple model is used to compute the resistance of the sulphur electrode as a function of charge. It is shown that the general network used for the simulation of the behaviour of the sulphur electrode can be simplified because of the relatively small value of the polarization resistance. Reasonable assumptions concerning the distribution of reactants and products are discussed. The model is able to assess the contribution of the sulphur electrode to the total cell resistance for a 16 Ah capacity cell.     

The partitioning of refactory metal elements in hafnium-modified cast nickel- base superalloys

Data from the electron microprobe have been used to elucidate the role of hafnium in altering the microstructure of the nickel-base superalloys B-1900, Alloy 713 LC, Udimet 700, and Mar-M246. The addition of about 1.3 to 2.0 pct Hf to these alloys improves their strength and ductility at both room temperature and 760°C. The data indicate that hafnium partitions to the surface of the MC carbides, replacing titanium and some molybdenum and/or tungsten in the carbide. On the basis of the observed morphology and composition of the carbides, it is postulated that, primarily, hafnium modifies the solidification sequence, which a) results in the formation of discrete, uniformly distributed MC carbides, b) retards the formation of secondary carbides, and c) contributes indirectly to solid solution strengthening of the matrix. Subsidiary of American Metal Climax, Inc. AMAX Division.     

Algorithm for tissue ischemia estimation based on electrical impedance spectroscopy

The purpose of this paper is to present an algorithm developed for real-time estimation of skeletal muscle ischemia, based on parameters extracted from in vivo obtained electrical impedance spectra. A custom impedance spectrometer was used to acquire data sets: complex impedance spectra measured at 27 frequencies in the range of 100 Hz-1 MHz, and tissue pH. Twenty-nine in vivo animal studies on rabbit anterior tibialis muscle were performed to gather data on the behavior of tissue impedance during ischemia. An artificial neural network (ANN) was used to quantitatively describe the relationship between the parameters of complex tissue impedance spectra and tissue ischemia via pH. The ANN was trained on 1249, and tested on 946 ischemic tissue impedance data sets. A correlation of 94.5% and a standard deviation of 0.15 pH units was achieved between the ANN estimated pH and measured tissue pH values.