Why I started the Thyroid Cancer Foundation.

[Our original introduction to "Listen to the Patient" is published again to emphasize the Journal's commitment to this important series.] For more than 50 years, Cancer has been devoted to exploring every facet of malignant neoplasia, from morphology to therapy, from epidemiology to biology, from historical perspective to basic science. One aspect, however, needs emphasis, namely, the human being who bears the burden of the cancer. For this reason and with the encouragement of the Editor, we have undertaken to remedy this situation by directing attention to the fears and frustrations, hopes and expectations, and feelings and thoughts of all kinds of the person who has cancer, who is worried about it, and who is dependent on physicians specialized in its diagnosis and management. For doctors to be understanding of the very deep needs of patients with cancer, it is requisite that they be privy to authentic, but often unspoken, expressions of a patient's anxieties about physical and emotional pain, loss of control over personal destiny, and plain dread of dying and of the end of cherished relationships. The essay that follows was written by a woman diagnosed with cancer who felt herself alone and in need of talking with others who faced the same diagnosis. Barrie R. Cassileth, Ph.D. Integrative Medicine Service, Memorial Sloan-Kettering Cancer Center, New York, New York A. Bernard Ackerman, M.D. Ackerman Academy of Dermatopathology, New York, New York.

Liquid phase combinatorial synthesis of benzylpiperazines.

A novel method for soluble, inexpensive polymer-supported synthesis of piperazine and piperidine libraries on the basis of nucleophilic benzylic substitution and N-acylation is reported. Disubstituted piperazine and piperidine derivatives, that are potential drug candidates, can be isolated in high yields and excellent purity by simple precipitation and washing. This liquid phase method proves to be a useful tool for constructing combinatorial libraries containing diamine moieties.

Sterol synthesis. A timely look at the capabilities of conventional and silver ion high performance liquid chromatography for the separation of C27 sterols related to cholesterol biosynthesis.

Sterol intermediates in the biosynthesis of cholesterol have recently assumed a very prominent position in a number of important problems in medicine and biology. In studies of these matters, the separation and identification of the sterol intermediates present formidable challenges, a situation which does not appear to be generally appreciated. High performance liquid chromatography (HPLC) is a simple and rapid approach for the separation of the concerned compounds. Reversed phase HPLC is very commonly used for this purpose. In the present studies, we have evaluated the capabilities of reversed phase, normal phase, and silver ion HPLC for the separation of sterols. Using an extensive collection of authentic sterols, our studies indicate very limited capabilities of reversed phase and normal phase HPLC for the separation of C27 sterols differing in the number and location of olefinic double bonds. In contrast, silver ion HPLC provided remarkable separations of the same compounds, either as the free sterols or their acetate derivatives. These findings, coupled with the results of recent studies of the properties of the same compounds by gas chromatography and by nuclear magnetic resonance and mass spectroscopy, have important implications regarding current application of methodologies for the separation, identification, and quantitation of sterol intermediates in cholesterol biosynthesis as critical portions of investigations on a number of current and emerging problems in biology and medicine.

Silver ion high pressure liquid chromatography provides unprecedented separation of sterols: application to the enzymatic formation of cholesta-5,8-dien-3 beta-ol.

We report that silver ion HPLC provides remarkable separations of C27 sterols differing only in the number or location of olefinic double bonds. This technique has been extended to LC-MS, analysis of purified components by GC, GC-MS, and 1H NMR, and to its use on a semipreparative scale. The application of this methodology for the demonstration of the catalysis, by rat liver microsomes, of the conversion of 7-dehydrocholesterol to cholesta-5,8-dien-3 beta-ol is also presented.

Identification and characterization of the GC-rich and cyclic adenosine 3',5'-monophosphate (cAMP)-inducible promoter of the type II beta cAMP-dependent protein kinase regulatory subunit gene.

A rat genomic clone containing 4.5 kilobases of 5'-flanking DNA and the first exon of the type II beta regulatory subunit (RII beta) of cAMP-dependent protein kinase was isolated, restriction mapped, and sequenced. The proximal 400-basepair promoter region was GC rich, lacked TATA/CAAT box motifs, and initiated transcription at multiple sites. Bandshifting and DNase-I footprinting experiments using this region of the RII beta promoter detected several related specific DNA-protein complexes formed using crude and fractionated nuclear extracts from rat ovary, brain, adrenal gland, and liver. All binding in these experiments mapped to a domain within the same region found to confer cAMP inducibility to a chloramphenicol acetyltransferase (CAT) reporter gene when transfected into primary cultures of rat granulosa cells. Although GC boxes (putative SP1-binding sites) and activator protein-2 (AP-2) elements were present in this functional region, and although expression vectors containing AP-2 sites conferred high levels of cAMP regulation of the CAT gene in cultured ovarian cells, neither the GC boxes nor the AP-2 sites were protected by footprint analyses or required for band shift activity of nuclear extract protein. These known regulatory elements, therefore, may be involved in functional activity of the RII beta promoter, but additional cis-acting DNA and trans-acting factors (yet to be characterized) also appear to interact with the functional promoter of the RII beta gene and regulate the hormone-specific expression of the A-kinase subunit in ovarian and neuronal cells.