ABSTRACT
It is predicted that the total number of mutations present at the first appearance of a fully malignant clone, including passengers, is so large that every individual patient's cancer is unique from the outset. The initiating (malignant-clone-defining) mutation set (McDMS) defines the cancer, permits absolute identification of cancer cells including all sub-clones, and thus suggests a mode of attack. Directly or otherwise, a useful proportion of the McDMS will give rise to gene products that can be detected and bound by external physical agents in a specific manner. Using such agents cooperatively, as a team, offers prospects for better diagnosis and treatment, especially if they are harnessed together in one molecule so that they can all bind to their targets at the same time without strain, because that will yield enhanced selectivity and strength of binding.
Subject(s)
Genetic Predisposition to Disease/genetics , Genetic Variation/genetics , Models, Genetic , Mutation/genetics , Neoplasms/genetics , Animals , HumansABSTRACT
In agarose gel electrophoresis, periodically inverting or interrupting the applied field may greatly accelerate the migration of polystyrene microspheres, in a manner varying with pulse times, and the observed zones are made sharper. The particles concerned are just large enough that under constant field they appear not to enter the gel at all or to migrate very slowly: and merely lowering the applied field may also enhance their electrophoretic migration, though to a lesser extent than with field pulsing. These effects may be accounted for by gel mesh flexibility which, varying with the nature of the migrating species, may either help or hinder migration.
Subject(s)
Electrophoresis, Agar Gel/methods , Microspheres , PolystyrenesABSTRACT
In vitamin A-deficient rats, the glutathione level in lung was diminished and microsomal lipid peroxidation much increased. In vitamin A-loaded animals, however, both were depressed below control. Thus vitamin A protection against lipid peroxidation is independent of glutathione.
Subject(s)
Glutathione/metabolism , Lipid Peroxides/metabolism , Lung/metabolism , Vitamin A/physiology , Animals , Microsomes/metabolism , Rats , Rats, Inbred Strains , Vitamin A Deficiency/metabolismABSTRACT
The isoenzymes of aspartate transaminase differ in their kinetic properties in that the cytoplasmic isoenzyme is more readily inhibited by adipate and by 2-oxoglutarate (substrate) at low pH. A differential kinetic assay based on this phenomenon has been optimised for use in assays of serum samples. The new method agrees well with an immune absorption procedure. Methods based on chromatographic separation of the isoenzymes fail in the presence of serum.
Subject(s)
Aspartate Aminotransferases/blood , Adolescent , Adult , Aged , Cytoplasm/metabolism , Female , Humans , Hydrogen-Ion Concentration , Isoenzymes/blood , Kinetics , Male , Middle Aged , Reference ValuesSubject(s)
Ferritins , Animals , Crystallization , Horses , Macromolecular Substances , Protein Binding , Protein Conformation , X-Ray DiffractionABSTRACT
In contrast to previous reports, an increase in glutamate dehydrogenase activity and no change in arginase activity were observed in rats fed a zinc-deficient diet for 15 weeks. The discrepancies could be due to a difference in degree and duration of zinc-deficiency.
Subject(s)
Arginase/metabolism , Aspartate Aminotransferases/metabolism , Glutamate Dehydrogenase/metabolism , Ornithine Carbamoyltransferase/metabolism , Urea/metabolism , Zinc/deficiency , Animals , Intestinal Mucosa/enzymology , Kidney/enzymology , Liver/enzymology , Male , Organ Specificity , RatsABSTRACT
A rapid and reproducible method is described for measurement of urea in biological materials (after deproteinisation) and in serum (without deproteinisation). Urea is colorimetrically determined with diacetyl monoxime and thiosemicarbazide in the presence of sulphuric acid, phosphoric acid and ferric chloride. The sensitivity of the colorimetric reaction and stability of the colour are enhanced over existing related procedures and the serum blank diminished, enabling urea to be precisely measured in micro amounts (1--5 microliters) of serum.
Subject(s)
Urea/blood , Chromogenic Compounds , Colorimetry , Diacetyl/analogs & derivatives , Methods , Protein Denaturation , SemicarbazidesABSTRACT
The separation of model protein pairs (hemoglobin/albumin, trypsin/chymotrypsin, hemoglobin A/hemoglobin F) was studied in an apparatus for preparative gel electrophoresis at loads up to 40mg/cm2 of the cross-sectional area of the gel bed. Separation was favored by higher ionic strength and by longer migration path. Under the conditions used and within the load range studied, increasing total protein load had no adverse effect but increased voltage gradient, temperature, or gel strength were all unfavorable.
Subject(s)
Electrophoresis, Polyacrylamide Gel/methods , Proteins/isolation & purification , Adult , Chymotrypsin/isolation & purification , Electrophoresis, Polyacrylamide Gel/instrumentation , Female , Hemoglobins/isolation & purification , Humans , Pregnancy , Serum Albumin, Bovine/isolation & purification , Trypsin/isolation & purificationABSTRACT
Volume exclusion gives rise to positive errors in the results of plasma or serum zinc determinations by methods in which protein is precipitated and the zinc extracted into solution. The error is amplified if two extraction steps are employed, and may be +20% or more. The same effects must be expected in any analysis involving comparable extraction procedures, whatever the substance being determined.
