Native Plasma Proteins

In the later discussion of the method for measuring Hp it is considered as established that haptoglobins are the only native plasma proteins which exist or may exist in normal or pathological mammalian plasma with a HbBC above 5 mg/100 ml, i.e., the lowest capacity measurable by routine methods. It is also assumed that native haptoglobins themselves have no affinity for heme. The suggestion by Jones et al. (J14) that rabbit Hp has affinity for heme still lacks supportive evidence and can therefore not yet be accepted. 

Fundamentals of Native Plasma Protein Adsorption on Polymer Surfaces... 

The packing material first described for direct injection of biological samples was prepared by simply saturating the accessible adsorption sites of a Cis reversed-phase silica with human plasma proteins (105). After saturation, the human plasma proteins were denatured at the external surface, and their native conformation was destroyed. With this treatment, the proteins formed a hydrophilic layer with weak ion-exchange properties, which provided protection from contact with the sample proteins, whereas the alkyl ligands inside the pores remained unchanged and thus served for analyte retention. The retention behavior of the saturated phase did not alter with this treatment, but the efficiency was reduced dramatically. Such protein-coated columns have shown a lifetime of several months (106). 

Marasmus Marasmus occurs when calorie deprivation is rela tively greater than the reduction in protein. Marasmus usually occurs in children younger than one year of age when the mother s breast milk is supplemented with thin watery gruels of native cereals, which are usually deficient in protein and calories. Typical symptoms include arrested growth, extreme muscle wast ing (emaciation), weakness, and anemia. Victims of marasmus do not show the edema or changes in plasma proteins observed in kwashiorkor. 

Diabetic patients are 3 4 times more susceptible to atherosclerosis and vascular insufficiency. The situation is similar for those suffering from renal insufficiency, independent of diabetes. Makita et al.5sl found that there was a direct correlation CP < 0.005) between serum AGE-peptide levels and renal function, as assessed by creatinine clearance. This led Bucala et a/.145 to consider that the modification of the plasma proteins, such as LDL, may arise due to the reaction with reactive, circulating AGE-peptides rather than glucose. AGE-LDL did form readily in vitro when native LDL was incubated with either synthesised AGE-peptides or AGE-peptides isolated directly from the plasma of patients. Such AGE-LDL exhibited markedly impaired clearance kinetics when injected into transgenic mice, expressing human LDL receptor. Their data indicate that AGE modification could contribute to elevated LDL levels in patients with diabetes or renal insufficiency. This hypothesis was further supported by the administration of AG to diabetic patients, when circulating levels of LDL decreased by almost 30%. Levels of Hb-AGE decreased too. 

Familial transthyretin amyloidosis (ATTR) is a hereditary degenerative disease which is closely associated with single amino acid substitutions in the plasma protein transthyretin (TTR), a 127 amino acid protein (Mr 13,761 Da) that is tetrameric in its native state.28 The clinical manifestations of ATTR are related to specific mutations of TTR (e.g., Val30 - Met and Thr60 — Ala). The definitive diagnosis is often established on the basis of the... 

D3. Daneshvar, B., Frandsen, H., Dragsted, L. O., Knudsen, L. E., and Autrup, H., Analysis of native human plasma proteins and haemoglobin for the presence of bityrosine by high-performance liquid chromatography. Pharmacol. Toxicol. 81, 205—208 (1997). 

Primary attachment occurs by both specific and non-specific mechanisms, and to the native surfaces of implanted biomaterials as well as to surfaces primed by adsorption of host-derived plasma proteins, extracellular matrix (ECM) proteins and coagulation products (platelets and thrombi) (Fig. 2) [20, 21],... 

Interleukin-2 Human recombinant lL-2 aldesleukin, proleukin des-alanyl-1, serine-125 human lL-2) differs from native lL-2 in that it is not glycosylated, has no amino terminal Ala, and has an Ser substituted for the Cys at amino acid 125. The potency of the preparation is represented in International Units in a lymphocyte proliferation assay such that 1.1 mg of recombinant lL-2 protein equals 18 million International Units. Aldesleukin has the following in vitro biologic activities of native lL-2 enhancement of lymphocyte proliferation and growth of lL-2-dependent cell lines enhancement of lymphocyte-mediated cytotoxicity and killer cell activity and induction of interferon-7 activity. In vivo administration of aldesleukin in animals produces multiple immunologic effects in a dose-dependent manner. Cellular immunity is profoundly activated with lymphocytosis, eosinophilia, thrombocytopenia, and release of multiple cytokines e.g., TNF-a, lL-1, interferon-7). Aldesleukin is indicated for the treatment of adults with metastatic renal cell carcinoma and melanoma. Administration of aldesleukin has been associated with serious cardiovascular toxicity resulting from capillary leak syndrome, which involves loss of vascular tone and leak of plasma proteins and fluid into the extravascular space. Hypotension, reduced organ perfusion, and death may occur. An increased risk of disseminated infection due to impaired neutrophil function also has been associated with aldesleukin treatment. 

Tanford, C. Preparation and Properties of Serum and Plasma Proteins. XXIII. Hydrogen Ion Equilibria in Native and Modified Human Serum Albumin. J. Amer. chem. Soc. 72, 441—451 (1950). 

To be clinically useful, dextrans have to be partially hydrolyzed to a molecular weight range comparable to that of plasma proteins. Furthermore, ethanol fractionation and extensive purification is required. The clinical dextrans used today are prepared from native dextran produced by the Leuconostoc mesenteroides NRRL B 512 strain (see Fig. 2). This dextran is only slightly branched, possessing 1 side chain for every 20 glucose units. Of the side chains, 85% comprise only 1-2 glucose units (Larm et al. 1971). 

Living cells adsorb (in multilayers) large amounts of water vapor at a vapor pressure corresponding to that of plasma or Ringer solution. So do solutions of gelatin, PVP, and DNA, but not those of native globular proteins. 

YHiile the fractional catabolic rate of low iodina-ted insulin is about 4-6, that of high iodinated is of the order of 2fo fully methylated or acylated insulins are degraded at the same rate of about 2 fof-m.n. (16).The peculiarity of these results lays in the fact that de-gradative processes, such as excessive iodination, usually lead to an increase in rate of catabolism of the proteins for instance, this behaviour is constantly observed in the case of plasma proteins. Hlfhen the separated chains at different level of iodine substitution, either in the reduced or in the fully sulphonated form, were studied in man their rate of catabolism was found to be of the same order of that of native insulin. On the other hand DAA insulin is degraded at a rate of the same order of that of native insulin. It may be worth to note that DAA insulin is biologically inactive, but its disulphide bonds are fully reactive. 

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