Progress in medical genetics. Volume 2 / edited by Arthur G. Steinberg.

Date:
1962
Catalogue details

Licence: Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)

Credit: Progress in medical genetics. Volume 2 / edited by Arthur G. Steinberg. Source: Wellcome Collection.

    30/392 (page 20)
    20 ARTHUR G. STEINBERG data) and of Inv(a) (Ropartz, Lenoir et Rivat, 1961) and Inv(b) (Stein¬ berg et al., 1962) is carried by gamma globulin. The Gm(a) substance has been shown by Grubb (1959a) to be stable to heating at 63 C. for one-half hour, to pH 12.3 at 37 C., to treatment with periodate, sulfhydryl compounds and with trypsin. He found that its ac¬ tivity was destroyed by crystalline papain and by pepsin and ficin. From these observations, he concluded that the activity is not included in the carbohydrate part of the molecule and that the Gm ( a ) activity is lost on the splitting of a very few bonds of the gamma globulin molecule. So far as I am aware, similar analyses have not been made for the other Gm fac¬ tors or for the Inv factors. Gm(a) specificity is absent from human milk (Grubb, 1959b; Lawler, 1960) and from human colostrum (Lawler, 1960). Since the gamma glob¬ ulin content of milk and colostrum is considerably less than that of serum, it would be of interest to repeat these experiments using SNagg aggluti- nators ( agglutinators from normal donors ) and concentrates of the gamma globulin from milk and colostrum. There is no information concerning the biochemical difference between Gm ( -j- ) and Gm ( — ) gamma globulin. It is unlikely, however, that the dif¬ ference is merely quantitative because no correlation between gamma globulin level ( excluding hypogammaglobulinemic individuals whose sera are inactive, as expected) and Gm (a) type appears to exist (Moullec et al., 1959; Grubb, 1959b; Martensson, 1961) and because of the absence of activity of Gm( —) and Inv( —) sera against SNagg agglutinators. Tests of the effect of heat (63 C. for one-half hour or until visible ag¬ gregates formed) on the action of Gm(a), Gm(b), Gm(x) and Gm-like against Ragg agglutinators showed that Gm(a-|-), Gm(b-t-) and Gm- ( x-|- ) sera remained positive after heating, while Gm-like ( -|- ) became Gm-like ( —); and that Gm (a—) and Gm(x—) became positive after heat¬ ing, while Gm(b—) and Gm-like ( — ) remained negative after heating (Steinberg and Stauifer, 1960). These data were interpreted as indicating that at least three qualitatively different molecules or active sites must exist for the determination of these factors, one for Gm(a) and Gm(x), a second for Gm ( b ), and a third for Gm-like. Martensson ( 1961) also concluded that Gm(a) and Gm(x) are probably carried by a single molecule and that Gm(b) is on another molecule. Mar¬ tensson based his conclusion on his finding that none of M-component gamma globulin extracted from the serum of 16 patients with myeloma was Gm(a-(- b-|-) (on the basis of population data eight Gm(a-(- b-j-) would have been expected to occur), while of the three samples classified for Gm(a), Gm(b) and Gm(x), one was Gm(a-1- b— x-f-); the other two were Gm (a— b-|- x—). It is argued that myeloma protein is of a single kind