Biomedical subjects

P G Conrad

Publications and source records attributed to P G Conrad.

5 recordsLinked to original sources

PubMed2001

Efficient detection of hereditary nonpolyposis colorectal cancer gene carriers by screening for tumor microsatellite instability before germline genetic testing.

BACKGROUND & AIMS: The optimal strategy for the detection of hereditary nonpolyposis colorectal cancer (HNPCC) gene carriers remains uncertain. We evaluated whether microsatellite instability (MSI) analysis or MSH2 and MLH1 protein immunostaining of tumors will screen individuals efficiently for germline MSH2 and MLH1 testing. METHODS: We performed a case-series study of 114 eligible families enrolled in our high-risk colorectal cancer (CRC) registry. Medical history data were collected on probands and relatives. MSI analysis was performed on proband tumors, and MSH2 and MLH1 protein immunostaining was assessed. Denaturing gradient gel electrophoresis was used to identify germline MSH2 or MLH1 mutations in probands found to have tumors with high-frequency MSI. RESULTS: Tumor tissue and adequate clinical data were available in 109 of the 114 families. Amsterdam criteria and Bethesda guidelines were met by 23% and 70% of the families, respectively. High-frequency MSI was identified in the proband tumors in 47 of the 109 families (43%). Germline MSH2 and MLH1 gene testing was carried out in the probands of 32 of 47 families with MSI-H tumors. Mutations were detected in 16 families (9 in MSH2 and 7 in MLH1) and sequence variants of uncertain significance in 5 families (1 in MSH2 and 4 in MLH1). Germline mutations or sequence variants of uncertain significance were detected in 15 of 19 (79%) of our Amsterdam families and in 6 of 13 (46%) of our non-Amsterdam families with MSI-H tumors. MSH2 and MLH1 protein immunostaining was assessed in 38 of the 47 MSI-H tumors. Unequivocal loss of hMLH1 expression was found in 20 tumors and loss of MSH2 expression in 9 tumors. Corresponding loss of protein expression was seen in 17 of 18 (94%) of tumors from probands with germline mutations or variants. CONCLUSIONS: The detection of high-frequency MSI or the loss of MSH2 or MLH1 immunostaining in CRCs are both useful criteria for selecting high-risk patients who should be tested for germline mutations in MSH2 or MLH1.

Colorectal Neoplasms, Hereditary Nonpolyposis↗

PubMed2001

A non-earthcentric approach to life detection.

The ultimate goal of a comprehensive life detection strategy is never to miss life when we encounter it. To accomplish this goal, we must define life in universal, that is, non-Earthcentric, measurable terms. Next, we must understand the nature of biosignatures observed from the measured parameters of life. And finally, we must have a clear idea of the end-member states for the search--what does life, past life, or no life look like (in terms of the measured parameters) at multiple spatial and temporal scales? If we can approach these problems both in the laboratory and in the field on Earth, then we have a chance of being able to detect life elsewhere in our solar system. What are the required limits of detection at each of those scales? What spatial, spectral, and temporal resolutions are necessary to detect life? These questions are actively being investigated in our group, and in this report, we present our strategy and approach to non-Earthcentric life detection.

Earth, Planet↗

PubMed2000

New phototriggers: extending the p-hydroxyphenacyl pi-pi absorption range.

[equation--see text] Introducing 3-methoxy or 3,5-dimethoxy substituents on the 4-hydroxyphenacyl (pHP) photoremovable protecting group has been explored with two excitatory gamma-amino acids, L-glutamic acid and gamma-amino butyric acid (GABA). These substituents significantly extend the absorption range of the pHP chromophore, e.g., the tail of absorption bands of 2a,b extend above 400 nm, well beyond the absorptions of aromatic amino acids and nucleotides. Irradiation releases the amino acids with rate constants of approximately 10(7) s(-)(1) and appearance efficiencies (Phi(app)) of 0.03-0.04. The photoproducts are formed through the pHP excited triplet and are primarily products of photoreduction and photohydrolysis. 1a,b also rearranged to the phenylacetic acid 3.

Acetophenones↗

PubMed1999

Life: past, present and future.

Molecular methods of taxonomy and phylogeny have changed the way in which life on earth is viewed; they have allowed us to transition from a eukaryote-centric (five-kingdoms) view of the planet to one that is peculiarly prokarote-centric, containing three kingdoms, two of which are prokaryotic unicells. These prokaryotes are distinguished from their eukaryotic counterparts by their toughness, tenacity and metabolic diversity. Realization of these features has, in many ways, changed the way we feel about life on earth, about the nature of life past and about the possibility of finding life elsewhere. In essence, the limits of life on this planet have expanded to such a degree that our thoughts of both past and future life have been altered. The abilities of prokaryotes to withstand many extreme conditions has led to the term extremophiles, used to describe the organisms that thrive under conditions thought just a few years ago, to be inconsistent with life. Perhaps the most extensive adaptation to extreme conditions, however, is represented by the ability of many bacteria to survive nutrient conditions not compatible with eukaryotic life. Prokaryotes have evolved to use nearly every redox couple that is in abundance on earth, filling the metabolic niches left behind by the oxygen-using, carbon-eating eukaryotes. This metabolic plasticity leads to a common feature in physically stratified environments of layered microbial communities, chemical indicators of the metabolic diversity of the prokaryotes. Such 'metabolic extremophily' forms a backdrop by which we can view the energy flow of life on this planet, think about what the evolutionary past of the planet might have been, and plan ways to look for life elsewhere, using the knowledge of energy flow on earth.

Adaptation, Physiological↗

PubMed1999

Genetic testing in hereditary colorectal cancer: indications and procedures.

Approximately 25% of colorectal cancers occur in younger individuals or those with a personal or family history of the disease, suggesting a heritable susceptibility. The minority of these cases are accounted for by one of the well-described hereditary colorectal cancer syndromes, familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal cancer (HNPCC). The recent identification and cloning of the genes responsible for FAP and HNPCC, along with other colon cancer susceptibility genes, has led to the wide-spread availability of genetic testing for hereditary colorectal cancer. Genetic testing raises clinical, ethical, legal, and psychosocial questions that must urgently be discussed. This review highlights areas of knowledge and uncertainty about genetic predisposition testing for colorectal cancer and provides clinicians with practical recommendations regarding the proper indications and procedures for this testing.

Adenomatous Polyposis Coli↗