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At least 991 records · Page 55Linked to original sources
PubMed1993

Immunotoxins: magic bullets or misguided missiles?

Thirteen years have passed since specific in vitro and in vivo killing of tumour cells by immunotoxins was first described. Why, then, has it taken so long to determine whether these drugs will have a major impact on the treatment of cancer, AIDS and autoimmune disease? The answer is that the transfer of basic discoveries to the clinic is a slow, multistep, interdisciplinary process. Thus, immunotoxin molecules must be designed and redesigned by the basic scientist depending on the efficacy and toxicity shown in vitro and in relevant experimental models. Next, each version must be evaluated by clinicians in humans through a lengthy process (1-3 years) in which the dose regimen is optimized and in which new problems and issues frequently emerge. These problems must again be modelled and studied in animals before additional clinical trials are initiated. In this article, Ellen Vitetta and colleagues discuss both basic and clinical aspects of the development of immunotoxin therapy.

Animals↗
PubMed1993

Immunotoxins: magic bullets or misguided missiles?

Thirteen years have passed since specific in vitro and in vivo killing of tumor cells by immunotoxins was first described. Why, then, has it taken so long to determine whether these pharmaceuticals will have a major impact on the treatment of cancer, AIDS and autoimmune disease? The answer is that the transfer of basic discoveries to the clinic is a slow, multistep, interdisciplinary process. Thus, immunotoxin molecules must be designed and redesigned by the basic scientist depending on the efficacy and toxicity shown in vitro and in relevant experimental models. Next, each version must be evaluated by clinicians in humans through a lengthy process (1-3 years) in which the dose regimen is optimized and in which new problems and issues frequently emerge. These problems must again be modeled and studied in animals before additional clinical trials are initiated. In this article, Ellen Vitetta and colleagues discuss both basic and clinical aspects of the development of immunotoxin therapy.

Animals↗
PubMed1987

An alternative to the magic bullet paradigm for specific cancer therapy.

To improve on current cancer therapies, which attack cells on the basis of their proliferative tendencies, much effort has been devoted to a search for properties of tumor cells that are tumor-specific rather than proliferation specific. Evidence from molecular genetic studies suggests, however, that most tumors may lack such properties. An alternative approach to therapy is described that is based on a property known to characterize the majority of human tumors; viz., a monoclonal origin. The strategy requires the prophylactic induction in tissues of mosaicism for genes dictating sensitivity or resistance to chemotherapeutic agents, and exploits the observation that any clone of cells arising in a mosaic tissue must inevitably differ from some other cells in the mosaic. Recent advances in genetic technology imply that the strategy is likely to be testable soon in animals, and that it may significantly improve the results of cancer therapy when a technology safe and efficient enough for its human implementation becomes available.

Antineoplastic Agents↗
PubMed1988

Biting the magic bullet. Radiolabelled monoclonal antibodies: the next great step forward in the diagnosis and treatment of cancer?

Optimism about the possible clinical applications of monoclonal antibodies has fuelled this burgeoning part biomedical research for nearly a decade. The highest expectations centre on the use of radiolabelled monoclonal antibodies in the diagnosis and treatment of cancer. This paper attempts to evaluate the claims for the new technology. A review indicates that the technique is having a limited impact on the practical management of patients. It is suggested that these limitations are mainly because the expected speed of transfer of the technology from research laboratory to clinic may have been previously exaggerated. In the long term the evidence reviewed in this paper suggests that radiolabelled monoclonal anti-tumour antibodies offer the potential of making the next great step forward in the diagnosis and treatment of cancer.

Antibodies, Monoclonal↗
PubMed1992

Ageing, information and the magical number seven.

Concepts from information theory are applied to human ageing. An equation is derived, based on the general properties of information systems, which closely predicts the mortality rate in old age. The same equation predicts that infection will be increasingly severe when first exposure to micro-organisms is delayed leading to diseases which peak in early and middle age. A parameter of the equation is the level of redundancy in human information processing. Observed mortality rates show that this is sevenfold and it is suggested that seven is a fundamental dimensionless biological constant.

Adult↗
PubMed1994

Spatial working memory score of humans in a large radial maze, similar to published score of rats, implies capacity close to the magical number 7 +/- 22.

To compare the working memory (WM) capacity of humans to rats, we tested humans with a 17-arm radial maze and, in a follow up experiment, with a 13-arm radial maze. Both mazes were 15.2 meters in diameter, painted on a grassy field. In one version of the 13-arm experiment, we required a concurrent nonsense vocalization to impede subjects' use of language to remember locations. Subjects were instructed to choose arms of the radial maze unsystematically--as rats generally appear to do--and to visit the end of each arm only once. In additional procedures, we tested working memory capacity in a verbal task that is more analogous to the radial maze than is the typical ordered recall test. Subjects were asked to try to recite a sequence of 17 numbers (i.e., 18 through 34) or letters (A through Q) in unsystematic order, with no repeats. In another experiment subjects recited 13 numbers (14-26) or letters (A-M). In all tests, subjects were allowed only as many responses as there were distinct items (17 or 13, respectively). Average correct-response (nonrepeat) scores were 14.4 for the 17-arm maze and 14.1 for both of the verbal 17-item tests; these scores are close to the reported score for rats in a 17-arm radial maze. Average scores were between 10.8 and 11.4 in all of the 13-item maze and recitation tasks.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

The magic and challenge of DNA probes as diagnostic reagents.

Molecular basis of hybridization and effect of different conditions, such as probe size, salt concentration, temperature, detergent concentration, time of washing, sample preparation and sample purity, on hybridization is discussed. Different formats of hybridization such as in solution hybridization, solid phase hybridization, and methods for probe preparation are presented. Polymerase chain reaction for the amplification of target and alternative methods for signal amplification are introduced in this review.

Blotting, Southern↗
PubMed1987

The new black magic: activated charcoal and new therapeutic uses.

Activated charcoal has been used for centuries as antidotal therapy for poisonings. New variations of charcoal therapy have developed over the last two decades. These modifications include multiple-dose activated charcoal (MDAC) therapy, charcoal hemoperfusion, and a new "superactive" charcoal (SAC). Recent literature suggests using initial charcoal therapy instead of ipecac as a first-line antidotal agent for many acute poisonings. The palatability of charcoal slurries has been enhanced by the addition of carboxymethylcellulose, sucrose, saccharin, chocolate syrup, or sorbitol. The new SAC has shown to adsorb 1.7 to 4 times the amount of substance tested compared with other activated charcoal preparations. Multiple-dose activated charcoal therapy has been shown effective in treating phenobarbital, digoxin, digitoxin, theophylline, and dapsone intoxications, among others. The problems associated with charcoal hemoperfusion therapy have been partially alleviated, and it is now alternative therapy for the seriously intoxicated patient.

Charcoal↗
PubMed1994

Cross-polarization dynamics in 2,6-dimethylbicyclo[3.3.1]nonane-exo-2-exo-6-diol inclusion compounds as studied by 13C magic-angle spinning nuclear magnetic resonance spectroscopy.

Solid-state 13C nuclear magnetic resonance (NMR) spectra of a number of inclusion compounds of 2,6-dimethyl-bicyclo[3.3.1]nonane-exo-2-exo-6-diol (host) with small organic small molecules (guests) have been studied. With 3,4-dichloro-1,2,5-thiadiazole and tetrachloroethylene as guests, line splittings of the host resonances were observed due to the location of the guest in the host lattice. The cross-polarization (CP) dynamics of these inclusion compounds have been studied and shown to be indicative of weakly coupled systems. As expected, the proton spin lattice relaxation times in the rotating frame (T1pH) of the host are increased by the presence of rapidly moving guest because the efficiency of homonuclear dipolar relaxation in the rotating frame is reduced. However, strong transient oscillations were also observed for the guest molecules during the Hartmann-Hahn transfer of magnetisation from the more abundant 1H spins to the 13C spins during spin lattice rotating frame relaxation. These oscillations were found to be greatest for carbons with largest chemical shift anisotropies.

Benzene Derivatives↗
PubMed1994

Residual interactions of a quadrupolar nucleus subject to high magnetic field and magic-angle spinning.

This is a theoretical study of nuclear magnetic resonance (NMR) spectra to be obtained from a powder specimen spinning in the magnetic field. The nuclear system is assumed to be magnetically dilute and to exhibit a combination of electric quadrupole interaction, magnetic shielding anisotropy and heteronuclear spin coupling. Formulas are given for the line positions and centreband linewidths of all transitions of the quadrupolar nucleus, in terms of scalar products of local interaction tensors. A number of unusual effects are predicted.

Anisotropy↗
PubMed1993

Magic Johnson.

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Adolescent↗