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While many individual risk factors have been defined for breast cancer, a family history was recognized long ago as one of the most potent. Mutations within BRCA1 or BRCA2, both identified about 10 years ago, are responsible for the majority of inherited breast cancer. By virtue of her age alone, a young woman diagnosed with breast cancer has a greatly elevated probability to carry a BRCA mutation. Other risk factors, including a personal or family history of ovarian cancer, bilateral breast cancer or Jewish ancestry, only serve to increase that chance. It is critical that clinicians caring for a young woman understand their patient's elevated risk to carry such a mutation and thoughtfully investigate this risk. Upon identification of a mutation in a young woman there are many consequences which necessitate careful consideration of various treatment and preventative options including prophylactic mastectomy and oophorectomy. Finally, the diagnosis of breast cancer in a young woman and the attendant genetic implications have immediate and serious consequences for her family members. Genetic professionals can help navigate the complex technical and psychosocial issues. This chapter explores the molecular, clinical and ethical intricacies of BRCA genetic testing. [ABSTRACT FROM AUTHOR]

Chymotrypsinogen has been successfully renatured in solution, after reduction of its 5 disulfide bonds in 6 M guanidine-HCl. This has been made possible by the study of the renaturation of a model derivative, polyalanyl-chymotrypsinogen. The reduced derivative is shown to refold and reoxodize spontaneously, with a 30-40% yield, into molecules which are monomeric and fully susceptible to activation by trypsin. Chymotrypsinogen can also be renatured but only in the presence of reagents allowing disulfide interchange and of moderate concentrations of guanidine-HCl or urea. These results illustrate how the kinetic trapping of incorrectly folded molecules by wrong S-S bonds and aggregation can be overcome, thus allowing the correct refolding of the protein. [ABSTRACT FROM AUTHOR]

The water proton relaxation times, T1 and t2, have been measured in solutions of free Gd(III) ions and in Gd(III) solutions containing lysozyme over a wide range of temperatures (0-40 °C) and nuclear frequencies (4-60 MHz) using pulsed nuclear magnetic resonance techniques. The equilibrium between lysozyme and Gd(III) has also been studied as a function of temperature. Water relaxation rates in both the free and enzyme-bound metal sites have been determined and closely fitted to existing theories over the complete range using a combination of graphical and computing technique. Values for the water co-ordination number (q) and the correlation time (τc) for the dipolar relaxation processes have been obtained and the rate processes contributing to τc have been analysed as a function of temperature and frequency. The values obtained for τc in the enzyme complex differ considerably from some earlier estimates. In the aquo-io relaxation is dominated by the rotational correlation time (τR) but in the enzyme-metal complex the electron spin relaxation time (τ8) becomes more important than other processes at low frequencies. Possible source of error in the data and assumptions made in the theoretical treatment are discussed. The implications of the results for mapping studies of lysozyme and other macromolecules, using magnetic resonance techniques are stressed. [ABSTRACT FROM AUTHOR]

Glycophorin A is the major membrane sialoglycoprotein of human erythrocytes and represents a typical example of a transmembrane glycoprotein. The functional role of this cell-surface component is not known but it represents a receptor for viruses, bacteria and parasites like Plasmodium falciparum. 1. Two cDNA clones encoding glycophorin A have been characterized from human fetal cDNA libraries. The longer cDNA extended from the coding region of glycophorin A (residues 4-131) to the 3' untranslated region which included two polyadenylation signals and a poly(A) tail. 2. The structural gene for glycophorin A is located on chromosome 4, q28-q31 as shown by in situ hybridization, thus confirming the previous localization by genetic linkage analysis. 3. Three distinct mRNA species (1.0 kb, 1.7 kb and 2.2 kb) have been identified in erythroid spleen. Northern blot analyses with a probe directed against the 3' untranslated region of the mRNAs indicated that all these species share a homologous 3' non-coding region and that the first polyadenylation signal downstream the stop codon is not used. 4. Preliminary studies by Southern blot analysis of the genomic DNA from normal En(a+) and rare En(a-) donors suggest that the glycophorin A gene has a complex organization and is largely deleted in donors of the Eh(a-) phenotype (Finnish type) who lack glycophorin A on their red cells. [ABSTRACT FROM AUTHOR]