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Light chain typing of M-components of non-macroglobulin nature from 500 sera gave a κ/γ quotient of 1.5. All the M-components contained either κ or γ chains. Irrespective of the electrophoretic charge the quotient in γG-M-components was 2, and in γA-M-components 0.9 and Bence-Jones proteinaemias 1.3. One serum contained a γGL- and a γAK-M-component, both in a concentration above 3 g per 100 ml.

Prospective studies of pregnant women were performed to compare individual variations in the plasma concentration of sex hormone binding globulin (SHBG) and pregnancy zone protein (PZP) during pregnancy, and to elucidate the degree of co-variation between these oestrogen sensitive proteins during gestation. The plasma concentration of SHBG manifested continuous increase reaching a 12-fold peak at delivery. The increase of the protease inhibitor PZP paralleled that of SHBG reaching a peak with a 25-fold increase by the beginning of the third trimester. Then it started to decline, while that of SHBG continued to increase. The synthesis of the protease inhibitor may also continue to increase during late gestation but its elimination from the circulation may be accelerated when the syncytiotrophoblastic area in contact with the maternal blood approaches its maximum. The unusually wide individual variation of PZP concentrations in non-pregnant women was confirmed. However, the individual levels increased proportionally during the progress of pregnancy, and we may speak of low, medium and high reactors for PZP. One initial conclusion to be drawn from the present findings is that the value of the plasma PZP concentration can only be interpreted from a pathophysiologic point of view if the patient's baseline level is known.

Prostate-specific antigen (PSA) is one of the three most abundant prostatic-secreted proteins in human semen. It is a serine proteinase that, in its primary structure, manifests extensive similarities with that of the Arg-restricted glandular kallikrein-like proteinases. When isolated from semen by the addition of chromatography on aprotinin-Sepharose to a previously described procedure, PSA displayed chymotrypsin-like activity and cleaved semenogelin and the semenogelin-related proteins in a rapid and characteristic pattern, but had no trypsin-like activity. About one third of the purified protein was found to be enzymatically inactive, due to cleavage carboxy-terminal of Lys145. Active PSA formed SDS-stable complexes with alpha 1-antichymotrypsin, alpha 2-macroglobulin-analogue pregnancy zone protein. PSA formed inhibitory complexes with alpha 1-antichymotrypsin at a molar ratio of 1:1, a reaction in which PSA cleaved the inhibitor in a position identical to that reported from the reaction between chymotrypsin and alpha 1-antichymotrypsin. The formation of stable complexes between PSA and alpha 1-antichymotrypsin occurred at a much slower rate than that between chymotrypsin and alpha 1-antichymotrypsin, and at a similar or slightly slower rate than that between PSA and alpha 2-macroglobulin. When added to normal blood plasma in vitro, active PSA formed stable complexes both with alpha 2-macroglobulin and alpha 1-antichymotrypsin. This complex formation may be a crucial determinant of the turnover of active PSA in intercellular fluid or blood plasma in vivo.

Epostane is a synthetic 17 alpha-alkylated 5 beta-androstane derivative, active following oral administration and devoid of any apparent androgenic, estrogenic or antiestrogenic potency. Circulating concentrations of 13 different plasma proteins were measured in eight women before and after 2 and 4 weeks of daily oral intake of 600 mg of epostane. The results were compared with those previously found during administration of the same daily dose of danazol, a synthetic 17 alpha-alkylated androgen derivative with known androgenic/anabolic activity. Epostane significantly suppressed serum levels of sex hormone-binding globulin, pregnancy zone protein and thyroxin-binding globulin and increased the levels of transthyretin. Haptoglobins, plasminogen and transferrin showed minor and/or transient changes and the levels of high density lipoproteins, alpha2-macroglobulin, albumin, C1-esterase inactivator, C3 complement and transcortin remained unaffected. The pattern of changes in plasma proteins was almost identical to that induced by administration of danazol, although the effects of epostane were somewhat weaker. Thus epostane is capable of inducing substantial changes in the pattern of steroid-sensitive plasma proteins in an androgen-like fashion despite its apparent lack of androgenic activity. The capacity of a steroid to induce such changes thus seems to be tied to the chemical structure rather than to the intrinsic hormonal activity of the molecule.

A genetic variant of human serum albumin (alloalbumin) exhibited atypical electrophoretic mobility and chromatographic behavior apparently because of the effect of a point substitution on the molecular conformation. Three forms of albumin were isolated by DEAE HPLC chromatography: normal albumin, and two variant forms V1 and V2. The point substitution (Asp-63 → Asn) generated a canonical tripeptide acceptor sequence for glycosylation with an N-linked oligosaccharide (Asn-Lys-Ser). Neuraminidase digestion followed by electrophoresis showed that the V2 variant form was glycosylated and the V1 form was not. Time-of-flight mass spectrometry yielded a molecular weight of about 2000 for the carbohydrate. Structural analysis of the carbohydrate was done by chromatographic comparison of the pyridylaminated derivatives with standards and was confirmed by proton NMR of the three pronase glycopeptides and of the pyridylaminated oligosaccharide. The oligosaccharide had a complex biantennary structure with two sialic acid residues. In normal albumin Asp-63 is exposed and is adjacent to the first disulfide bond, Cys-62 → Cys-53. The apparent effect on molecular conformation resulting in incomplete glycosylation and atypical electrophoretic mobility suggests that glycosylation may interfere with disulfide bond formation at this site.

Plasma samples exhibiting alloalbuminemia on electrophoresis at pH 8.6 were requested from clinical laboratories throughout Sweden. Nine variants, each representing a different single point mutation, were found in 100 apparently unrelated Swedes. The overall prevalence of alloalbuminemia was estimated at 1:1700. Mutations were identified by protein-structural analysis followed by allele-specific DNA hybridization to verify the most common types. Slightly retarded (+1) mobility was seen in 80 cases. Of these, 71 had the Arg(-2)----Cys proalbumin variant previously called Malmö I proalbumin. Thirteen examples of the second most frequent type, the substitution Lys313----Asn and a mobility change of -1 charge unit, were found, as well as six cases of Glu570----Lys (albumin B) and a single case of Arg-1----Gln (proalbumin Christchurch). Five previously unreported types of alloalbuminemia were identified: four instances of Glu376----Gln, which is the second known mutation at this site; two examples of Asp550----Ala, the second mutation reported at this site; and one example each of Asp63----Asn, Gln268----Arg, and Asn318----Lys. Other mutations were identified among eight subjects of foreign descent. The high frequency and relatively uniform geographic distribution of the Arg-2----Cys mutation suggest that it may have occurred in a founder individual many generation ago in Sweden.

The concentrations of 25 plasma proteins were measured in 29 patients with chronic renal insufficiency. All the patients had terminal renal failure and were treated with intermittent hemodialysis, but were otherwise in good general condition at the time of investigation. The plasma levels of 8 proteins with M(r) < 50 kD were significantly elevated compared to normal subjects. In contrast, only 2/17 proteins of greater size were found in increased concentrations. The degree of increase in concentration differed substantially between individual low molecular weight proteins, suggesting a complex metabolism in addition to delayed renal elimination. Acute phase proteins and immunoglobulins were not affected by renal insufficiency per se, although erythrocyte sedimentation rates were generally high. The synthesis of acute phase proteins increased normally during the course of inflammation. We conclude that although the sedimentation rate is of no value, complicating inflammatory processes can be traced by quantitative analysis of acute phase proteins, including C-reactive protein, even in patients with severe chronic renal insufficiency.

The crystal structure of proteolytically modified human alpha 1-antichymotrypsin (ACT), a member of the serpin superfamily, has been solved by Paterson search techniques and refined to an R-factor of 18.0% at 2.7 A resolution with mean deviations from standard bond lengths and angles of 0.013 A and 3.1 degrees, respectively. The final model consists of 374 amino acid residues, 126 solvent molecules and five sugar residues. Asn70 could be identified unambiguously as a glycosylation site and Asn104 is probably also glycosylated. The structure of cleaved ACT is compared with cleaved alpha 1-antitrypsin (alpha 1 PI) and with plakalbumin, which are prototypical models for cleaved and intact serpins, respectively. Cleaved ACT is very similar to cleaved alpha 1 PI; in particular, it has strand s4A, which is liberated by proteolysis, inserted as the middle strand in beta-sheet A. ACT and alpha 1 PI differ locally only at sites of insertions, except at the segment s3C-turn-s4C, which is displaced by several angström units. This region of ACT is involved in DNA binding.

Crystal structure studies have shown that cleaved and intact serpins differ essentially in the topology of beta-sheet A. This is five-stranded in the intact molecules and six-stranded after cleavage by insertion of strand s4A whose C-terminus has become free [Löbermann, H., Tokuoka, R., Deisenhofer, J.Huber, R. (1984) J. Mol. Biol. 177, 531-556; Wright, T. H., Qian, H. X.Huber, R. (1990) J. Mol. Biol. 213, 513-528]. The structural transition is accompanied by changes in spectral properties and an increase in thermal stability. We show here that an N alpha-acetyl-tetradecapeptide with the amino acid sequence of strand s4A, residues 345-358 of human alpha 1-antitrypsin, associates with intact alpha 1-antitrypsin and forms a stoichiometric complex with properties very similar to cleaved alpha 1-antitrypsin. Complex generation has the characteristics of a folding process.

An electrophoretically slow albumin variant was detected with a phenotype frequency of about 1:1000 in Sweden and was also found in a family of Scottish descent from Kaikoura, New Zealand, and in five families in Tradate, Italy. Structural study established that the major variant component was arginyl-albumin, in which arginine at the -1 position of the propeptide is still attached to the processed albumin. A minor component with the amino-terminal sequence of proalbumin was also present as 3-6% of the total albumin. After amplification of the gene segment encoding the prepro sequence of albumin, specific hybridization of DNA to an oligonucleotide probe encoding cysteine at position -2 indicated the mutation of arginine at the -2 position to cysteine (-2 Arg----Cys). This produced the propeptide sequence Arg-Gly-Val-Phe-Cys-Arg. This was confirmed by sequence analysis after pyridylethylation of the cysteine. This mutation produces an alternate signal peptidase cleavage site in the variant proalbumin precursor of arginyl-albumin giving rise to two possible products, arginyl-albumin and the variant proalbumin. Another plasma from Bremen had an alloalbumin with a previously described substitution (1 Asp----Val), which also affects propeptide cleavage. Hypermutability of two CpG dinucleotides in the codons for the diarginyl sequence may account for the frequency of mutations in the propeptide. Mutation at these two sites results in a series of recurrent proalbumin variants that have arisen independently in diverse populations.

1. Monomeric nu-chains were conjugated with CNBr-activated Sepharose 4B. The C-terminal cysteine of the conjugated nu-chain was converted to a mixed disulfide with 3-carboxy-4-nitro-benzenethiol (Nbs) and used to separate plasma proteins with reactive thiol groups. The plasma proteins, alpha1-antitrypsin and prealbumin have the greatest affinity for the interchange reaction with mixed disulfides. The disulfide link between alpha1-antitrypsin and nu-chain is sensitive to excess Nbs, and is selectively cleaved in the presence of 5,5'-dithiobis(2-nitrobenzoate) (Nbs2) which accepts the sulfhydryl group of alpha1-antitrypsin. 2. A Simple method developed for the isolation of human alpha1-antitrypsin was equally effective for the various inherited phenotypes and for alpha1-antitrypsin from the dog, baboon, and monkey, Glutathione-Sepharose was also used successfully, but the nu-chain conjugate yielded alpha1-antitrypsin less contaminated with mercaptalbumin and prealbumin. 3. The alpha1-antitrypsin is harvested from this procedure as a mixed disulfide with Nbs. The negative charge of Nbs at pH 8.1 causes an increased electrophoretic mobility of the alpha1-antitrypsin derivative. Mild reduction liberates Nbs and electrophoretic mobility of alpha1-antitrypsin returns to normal. The method described can increase the alpha1-antitrypsin content of a plasma fraction from 5% of the total protein to 95% within one day with a yield of about 50%. This purification procedure does not exert any detectable effect on microheterogeneity.

The terminal cysteinyl of light Ig chains of the κ type (κ-chains) can be used for separation of plasma protein by thiol-disulfide interchange reactions. The interaction between Sepharose-conjugated κ-chains and α1-anti-trypsin (α1AT) was studied with the cysteine of one or both of the two proteins either reduced or activated by 5,5′-dithiobis-(2-nitrobenzoic acid) (Nbs2). The largest amounts of complexes were formed with the terminal κ-chain cysteine activated by Nbs2 and with the single cysteine of α1-anti-trypsin reduced. Cysteine and five related thiol compounds were conjugated with Sepharose 4B or 6B to explore the preparative use of this type of interchange reaction. The capacity of the Nbs2-activated form of κ-chains and of the six thiol compounds to link plasma proteins was studied. Bound proteins were eluted after reduction with 2-mereaptoethanol and were analyzed immunochemically for 10 of the plasma proteins having more or less reactive thiols. The elution patterns varied widely. 3-Thio-2-hydroxypropyl-Sepharose showed very high selectivity for linkage of albumin at pH 8.1, while cysteine preferably linked α1AT and IgA. Substitution of the carboxylate group of cysteine increased the linkage of albumin. Thus, Sepharose-linked thiol compounds seem useful for the fractionation of proteins with reactive thiols and for the separation of proteins with and without reactive thiols.

The electrophoretic seminal plasma protein pattern changes obviously within a few hours if the plasma is not frozen after the ejaculation. Mainly cathodal proteins disappear. Addition of serine protease inhibitors has no apparent affect, but o-phenanthroline markedly retards the conversions seen on electrophoresis. The subcellular organelles in seminal plasma are shown to contain a zinc ion dependent peptidase with optimal activity at pH 7.8. Estimations of enzyme activity may be performed using the elastase substrates n-tert butyloxycarbonyl-L-alanine-paranitrophenylester (Boc(Ala)) and succinyl(alanine)3-paranitroanilide (Suc(Ala)3pNA). The enzyme is inactivated by addition of o-phenanthroline and is completely reactivated by the addition of zinc ions.

The sequence of alpha 1-antitrypsin is in keeping with its role as a tissue scavenger of leukocyte elastase. Two abnormal variants commonly present in Europeans cause a deficiency that predisposes them to a progressive loss of lung elasticity. The nature of the reactive centre helps explain why cigarette smoking greatly accelerates the onset and severity of this degenerative process to give the disease emphysema.

Liquefaction of coagulated human semen was inhibited by o-phenanthroline; subsequent addition of Zn2+ reversed this inhibition, but not if the coagulum was repeatedly washed before Zn2+ was added. No liquefaction of the coagulum occurred when Fe2+ was added (in a 1:3 molar ratio to o-phenanthroline), and the gel repeatedly washed. This o-phenanthroline-depleted coagulum was liquefied by resuspended pellet from ultracentrifuged pooled seminal plasma. In denatured and reduced semen coagulate, we identified the 52 kDa, 71 kDa, and 76 kDa protein bands of the predominant seminal vesicle protein. The protein was not present in the supernatant after centrifugation of coagulated semen, and it was degraded to several minor basic proteins when semen liquefied. These findings imply that the predominant seminal vesicle protein functions as the structural protein of coagulated semen. In much the same way as in ejaculated semen, the 52 kDa, 71 kDa, and 76 kDa protein bands in seminal vesicle secretion collected postmortem were digested to minor basic proteins after incubating the secretion with resuspended pellet from ultracentrifuged seminal plasma. This pellet contained the membrane-bound succinyl(alanine)3-p-nitroanilide hydrolysing peptidase of prostatic origin which, like the liquefaction process, was active in the presence of EGTA, inhibited by non-chelated Zn2+, and inactivated by o-phenanthroline--an inactivation that was reversed by Zn2+.

15 patients with active RA were observed over a 3-month period after starting chloroquine treatment. Clinical condition, plasma levels of chloroquine and levels of 15 individual plasma proteins were checked monthly. Nine patients responded favourably to therapy, 6 failed to respond. The responders had lower initial CRP, orosomucoid and ceruloplasmin levels, whereas their IgA and IgM levels were slightly elevated. Significant reductions in the levels of CRP, haptoglobin, orosomucoid, fibrinogen and ceruloplasmin occurred in the responder group of patients. Alfa1-antitrypsin, antichymotrypsin C3 and C4 levels within the normal range were frequently encountered despite other clear-cut signs of activity. The chloroquine levels did not differ between responders and non-responders, the mean concentrations being 1.04 and 1.6 micromol/l respectively. This study has also demonstrated that in selected cases, despite active joint disease, all acute phase proteins may be normal. Finally, it was obvious that chloroquine, even when inducing remission, only brought about a partial normalization of the plasma protein pattern.

The predominant protein in human seminal vesicle secretion constitutes the structural protein of coagulated semen. This high molecular weight protein (HMW-SV-protein) is stable in seminal vesicle secretion during in vitro storage at 37 degrees C for at least 20 h, but is rapidly cleaved on mixing with prostatic proteases. Seminal coagulate, washed free of soluble components, is dissoluble by 2 to 3 mol/l of guanidine-HCl. Although dithiothreitol added to seminal coagulate does not liquefy the clot, complexes between HMW-SV-proteins are broken up by reduction under denaturing conditions, which suggests that the non-covalent linkages of HMW-SV-proteins are essential in the clot. Prostatic proteases cleave the HMW-SV-protein during liquefaction of ejaculated semen to a series of labile proteins. These proteins are further cleaved to peptides of successively decreasing size after completed liquefaction. The cleavage of the HMW-SV-protein is the major cause of the fast shift of the electrophoretic pattern of seminal proteins if semen is stored without protease inhibitors.

The S variant of the human alpha 1-antitrypsin with E-264----V, is responsible for a mild alpha 1-antitrypsin deficiency quite common in the European population. S protein specifically cleaved at the susceptible peptide bond was crystallized and its crystal structure determined and refined to 3.1 A resolution. The S variant crystallizes isomorphous to the normal M variant. The difference Fourier electron density map shows the E----V change as outstanding residual density. In addition, small structural changes of the main polypeptide chain radiate from the site of mutation and affect parts far removed from it. By the mutation, internal hydrogen bonds and salt linkages of E-264 to Y-38 and K-487, respectively, are lost. They cause the far-reaching slight distortions and are probably related to the reduced thermal stability of the S mutant. They may also be responsible for slower folding of the polypeptide chain and the clinical symptoms of alpha 1-antitrypsin deficiency. In a theoretical study by molecular dynamics methods simulations of the M and S proteins were made and the results analysed with respect to structural and dynamic properties and compared with the experimental results. There is a significant correlation between experimental and theoretical results in some respects.

Analysis of 25 plasma proteins was performed on blood drawn from 7 females before and during treatment with danazol. This steroid was found to induce a pattern of plasma protein changes similar to but not identical with that of other 17 alpha-alkylated anabolic steroids. For comparison, the same 25 plasma proteins were analyzed in blood from pregnant women in their third trimester, when the estrogen influence on plasma protein synthesis is most pronounced. Five major types of response were found. 1) Albumin and orosomucoid were not influenced by danazol or, after correction for volume expansion, by pregnancy. 2) Prealbumin, C1-esterase inhibitor, and haptoglobins increased substantially during danazol treatment but were not significantly influenced by pregnancy. 3) Transferrin, antithrombin III, prothrombin, and plasminogen showed marked increases after administration of danazol and during pregnancy. 4) Transcortin, ceruloplasmin, and alpha 1-antitrypsin doubled in pregnancy but were not influenced by danazol. 5) The concentrations of T4-binding globulin, pregnancy zone protein, and sex hormone-binding globulin more than doubled in pregnancy, and all three decreased to one third or less on administration of danazol. The plasma estradiol content fell correspondingly. The different types of plasma protein response found in these two groups of patients fit the hypothesis that hepatocytes contain steroid receptors capable of reacting with estrogens and/or other steroids such as danazol and, thus, influence the biosynthetic rate of many but not all plasma proteins according to a specific pattern. The synthesis of some of the estrogen-sensitive proteins is depressed after intake of danazol, which suggests that there is a competition for the receptors in the hepatocytes as there is for other estrogen target tissues.

The earlier observed pronounced hypogammaglobulinemia in germfree rats of different ages has been confirmed. Using an immunologic technique the concentration of immunologic gamma globulins were found to vary between 10 and 15 per cent of the values observed in ordinary rats. Upon contamination of germfree rats with the normal microbial flora a pronounced lag phase was noted before the gamma globulin level became normal. This lag phase was most pronounced in growing rats. Newborn rats seem to start gamma globulin production more rapidly than older germfree rats. The response with regard to gamma globulin production on contamination of germfree rats with different types of bacterial cells through the natural routes is not identical.

The authors report the concentration of some plasma proteins after administration of mestranol and/or chlormadinone in 19 controls and 43 women who had had recurrent cholestasis during previous pregnancies. Mestranol alone and combined with chlormadinone acetate induced enhanced βIC-globulin and fibrinogen and depressed cold insoluble globulin level. The changes were, if anything, more marked in women with cholestasis during an earlier pregnancy. No change of antichymotrypsin or C-reactive proteins was found in any of the groups. Chlormadinone acetate alone produced no apparent alterations in the plasma protein pattern.

A serum containing an M-component of IgM type gave on immunoelectrophoresis a biarcuate precipitation line. The anodal arch was produced by subunits of IgM, the other, by polymeric (17 S) IgM. The subunits combined in other optimal proportions with anti IgM than polymeric IgM as shown by e.g. immunoelectrophoresis and antigen-antibody crossed electrophoresis. Changes in immunoprecipitation patterns after reduction with mercaptoethanol of the cathodal arch to a mobility more equal to the anodal arch is one way to trace IgM subunits in plasma.

(1965). Electrophoretic Microheterogeneity of Serum α1-Antitrypsin. Scandinavian Journal of Clinical and Laboratory Investigation: Vol. 17, No. 3, pp. 271-274.

The response of 18 plasma proteins after cholecystectomy has been followed up for 3 weeks. The acute phase reaction has been compared with that after mastectomy. The response to these tissue lesions were very similar but more intense after cholecystectomy. The finding suggest that a2-macroglobulin may be used as an internal standard since no apparent changes appear. The concentration decreases during the first few postoperative days for albumin, α-lipoproteins, transferrin and prealbumin. No common cause is probable. C-reactive protein and antichymotrypsin begin to rise within eight hours. One day later orosomucoid, fibrinogen, haptoglobin and α1-antitrypsin show a strong reaction. Hemopexin, β1c-globulin, prothrombin, ceruloplasmin, Gc-globulin, α1, easily precipitable glycoprotein, plasminogen and cold insoluble globulin showed a delayed reaction with a moderate increase within a week. The immunoglobulins show insignificant changes.

The serum concentrations of α1-antitrypsin and α2-macroglobulin were determined immunochemicaHy in 50 cases with α1-antitrypsin deficiency. The mean α1-antitrypsin concentration was found to be 14.5 per cent and the mean α2-macroglobulin concentration 134 per cent of the normal concentration. No significant difference could be demonstrated between subjects with and without chronic lung disease. The trypsin inhibiting capacity of the inter-α trypsin inhibitor was estimated in two serum pools from subjects with and without pulmonary disease after separation of the serum inhibitors by gel filtration. It was found to be normal in both.

The main constituents of the a,-fraction obtained on paper electrophoresis in a barbital buffer are α1-lipoproteins, orosomucoid (acid glycoprotein), Schmid's (1953) and Schultze et al.'s α1-3.5 S ...

A short survey is given of the literature on haptoglobin, the hemoglobin-binding serum protein, its properties and biologic variations. The principles of an electrophoretic method for quantitative determination of the serum haptoglobin are described. Electrophoretic studies showed that haptoglobin has a high affinity for hemoglobin at physiologic pH and that every haptoglobin molecule can bind at least 2 hemoglobin molecules. Observations made following the intravenous injection of hemoglobin showed: that hemoglobin administered intravenously is bound by the haptoglobin; that free hemoglobin is not demonstrable until more hemoglobin has been injected than can be bound by the haptoglobin; that the complex hemoglobin-haptoglobin is eliminated from the plasma after intravascular hemolysis or intravenous administration of hemoglobin without being excreted in the urine; that the hemoglobin-haptoglobin complex is removed from the plasma at a constant rate during the major part of the elimination period; that the haptoglobin level will fall to nil within 24 hours, if the amount of hemoglobin injected is sufficient to bind all the haptoglobin available. During the following days the rate of formation of haptoglobin can be studied. From the data available it can be concluded that hemoglobinuria cannot appear until the amount of hemoglobin administered intravenously or the amount liberated intravascularly exceeds the binding power of the haptoglobin and the reabsorption capacity of the tubules. The variation observed by earlier authors in the so-called renal threshold for hemoglobin on intravenous injection of hemoglobin can be explained among other things by the variation in the haptoglobin content in one and the same subject, i.e., if the haptoglobin level is low, the threshold value will also be low, and vice versa.

Complexes between κ chains and plasma proteins were regularly found in sera from patients with Bence-Jones proteinuria of type κ but not of type λ. These complexes are preferentially formed with prealbumin and α 1 -antitrypsin. They are split by mercaptoethanol.

Cumulative knowledge of the protein composition of plasma and newer techniques for specific analysis of proteins have made obsolete most flocculation tests, the albumin:globulin ratio, scanning diagrams, and most determinations of electrophoretic fractions. More clinically relevant information about the serum protein composition is obtained by critical visual evaluation of the protein bands obtained after electrophoretic separation of plasma or serum in nonadsorptive supporting media, if supplementary specific analysis is made of a small number of proteins such as albumin, orosomucoid, haptoglobins, ceruloplasmin, and the immunoglobulins of the three predominant classes

The serum content of α1-antitrypsin was estimated with immunoprecipitation in tubes utilizing a specific antiserum. The results agreed with those obtained in association with the determination of the total antitryptic activity of serum in members of families with hypo-α1-antitrypsinemia. No overlapping occurred between normals, hetero- and homozygotes. The non-α1-antitrypsins of 1 ml serum inhibited in the average 0.15 mg trypsin.

Laurell, C.-B. and E. Morgan. Iron exchange between transferrin and the placenta in the rat. Acta physiol. scand. 1964. 62. 271–279. — The process of iron exchange between transferrin and the placenta was studied in vitro using 59Fe, rat serum or purified rat transferrin labelled with 131I and placental tissue. The yolk sac placenta bound more transferrin and took up iron more rapidly than did the allantoic placenta. The amount of transferrin bound increased rapidly for the first 15 minutes but thereafter showed little further increase: the amount bound increased as the transferrin concentration was increased but was unaffected by the degree of its saturation with iron. Iron uptake increased steadily during incubation, was greater when the iron concentration was increased, but was unaffected by increasing the transferrin concentration with a constant iron concentration. The release of iron from placenta was slower than that of transferrin and was less into a transferrin-free solution than into plasma. The intravenous injection of rat transferrin in amounts sufficient to approximately double the plasma concentration did not alter the subsequent transfer of 59Fe from maternal plasma to the fetuses. The results show that the mechanism of iron exchange between transferrin and rat placenta is very similar to that between transferrin and reticulocytes.