Digital dermatoglyphics in mammary cancer.

Fingerprints from 200 women with histologically proven breast cancer (case group) were compared to fingerprints from 138 women with no history of any malignant disease (control group). Of the patterns analyzed, four were significantly associated with breast cancer: accidentals, transitionals, angled ulnar loops, and horizontal ulnar loops. A fifth print, the angled radial loop, was found to be of borderline importance as an independent predictor of breast cancer. Of 200 patients in the case group, 27 had one or more accidental prints, 58 had one or more transitionals, 34 had one or more horizontal ulnar loops, and 93 had one or more angled ulnar loop patterns. In 138 control subjects there were 2 with accidental patterns, 21 with one or more transitionals, 6 with horizontal ulnar loops, and 16 with one or more angled ulnar loops. In addition, there appeared to be a gradient of risk; a woman with one type of suspicious print is at higher risk of breast cancer than a woman with none, and two suspicious prints indicate a higher risk than does one. If these findings are confirmed, the prints described will represent a noninvasive anatomical marker of breast cancer risk.

In vivo study of lactoferrin and murine rebound myelopoiesis.

Lactoferrin has been reported to inhibit the production of colony-stimulating factor (CSF); thus we sought to study its possible effects on myelopoiesis in vivo. The characteristics of rebound myelopoiesis in C57BL mice injected with a sublethal dose of cyclophosphamide (CY) were used to test lactoferrin for any granulopoietic activity. An experimental group received daily injections of 50 micrograms of human lactoferrin beginning 24 hr after CY injections. By measuring the total nucleated cellularity of the femoral marrow, the peripheral blood count, and the incorporation of tritiated thymidine by the marrow in six replicate experiments, no statistically significant difference was noted between the lactoferrin injected groups and the control groups. Neither the route of lactoferrin administration (i.v. or i.p.) nor the sex of the animal altered the myelopoietic recovery. Lactoferrin had no stimulatory or inhibitory effect on murine rebound myelopoiesis in vivo contrary to the reported in vitro results.

Sepharose-linked concanavalin A in the purification and characterization of glycoprotein hormones of the bovine pituitary.

Affinity chromatography on concanavalin A-Sepharose is a time saving step in both large and small scale isolations of the bovine pituitary glycoprotein hormones. After ion-exchange chromatography, the final yield of purified lutropin is 40-50% of material in starting concentrates and of purified thyrotropin is approximately 20%. The final products have the same electrophoretic and immunological properties and amino acid compositions as previous preparations. Less than 3% of the immunoreactive lutropin, follitropin and thyrotropin are present as non-glycosylated forms in either crude pituitary extracts or concentrates. Thyrotropin and follitropin elute from the immobilized lectin as a single fraction, whereas lutropin separates into two glycosylated fractions. Gel filtration of both crude extracts and the glycoprotein fractions shows that less than 5% of the immunoreactivity of the hormones is present as material of apparently high molecular weight. Substantial alpha subunit immunoreactivity, however, is in three fractions (as found by others in human pituitary extracts) corresponding to "high molecular weight material" (7%), intact hormones (46%) and free subunit (47%).

Structure and structure-function relationships in glycoprotein hormones.

Relationships between the sequences of thyrotropin (thyroid-stimulating hormone, TSH), lutropin (luteinizing hormone, LH), human choriogonadotropin (chorionic gonadotropin, hCG) and follitropin (follicle-stimulating hormone, FSH) are now well established. Each beta-subunit contains six disulphide bonds and considerable homology is seen when all four linear sequences are aligned with half-cystine residues in juxtaposition. Major questions about the tertiary structures of the subunits and their interactions to form active hormone remain. Determination of the disulphide bridges in both alpha- and beta-subunits has not yielded to usual methods and conflicting data about the alpha-subunit have been reported. Partial reduction of the beta-subunits of LH and TSH with subsequent labelling of the cysteines formed has shown that a single bond is first reduced. This bond is between positions 93 and 100 in LH-beta and the corresponding positions 88-95 in TSH-beta. Thus, as would be expected from the fact that interhormone hybrids can be made with the common alpha-subunits, the chemical data, though still limited, indicate similar tertiary structures for the different beta-subunits. To investigate whether other useful intermediates can be obtained after partial reduction, we have studied reduction and derivative formation in various conditions. Intact LH is more resistant to reduction than either its alpha- or beta-subunit but no intermediates have been observed which are not present after partial reduction of individual subunits. Preliminary experiments on the reoxidation of fully reduced alpha-subunit show that the reoxidized material will recombine with native beta-subunits to yield biologically active TSH or LH. Studies from this and other laboratories on chemical modifications of several amino acid residues of glycoprotein hormones and their subunits are also summarized.

The carboxylic acid groups of bovine luteinizing hormone. The effects of their modification on receptor site binding and subunit-subunit interaction.

The modification of the carboxyl groups of the subunits of bovine luteinizing hormone to neutral derivatives by carbodiimide-mediated coupling with glycine methyl ester has been studied. The modified alpha subunit, which has 8 residues of glycine methyl ester incorporated, will no longer recombine with native beta (hormone-specific) subunit, but the modified beta subunit, with 6 to 7 glycine methyl esters incorporated, will recombine with native alpha to yield a partially active hormone. Derivatization of the intact hormone results in dissociation to subunits together with formation of a major side product which is covalently cross-linked. Significant cross-linked product was not obtained during modification of individual subunits, thus indicating an orientation between an activated carboxyl group(s) and a nucleophile(s) in the intact hormone which favors coupling. Separation of subunits from the derivatized, noncross-linked fraction by countercurrent distribution reveals a heterogeneous preparation of the modified alpha subunit which also will not recombine with either a native or modified beta subunit. The beta subunit from the modified intact hormone was indistinguishable from the modified isolated beta subunit in amino acid composition and in ability to recombine with native alpha subunit. The results are consonant with data from this and other laboratories in which various modifications of the alpha chain, the subunit common to the glycoproteins, more seriously affect recombination than similar modifications of the beta subunits. The number of carboxyl groups modified in each subunit is compatible with but not in total agreement with assignments of amides reported from sequence studies.