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Biomedical subjects

L Lipton

Publications and source records attributed to L Lipton.

7 recordsLinked to original sources
PubMed2002

Whole-gene APC deletions cause classical familial adenomatous polyposis, but not attenuated polyposis or "multiple" colorectal adenomas.

Familial adenomatous polyposis (FAP) is a dominantly inherited colorectal tumor predisposition that results from germ-line mutations in the APC gene (chromosome 5q21). FAP shows substantial phenotypic variability: classical polyposis patients develop more than 100 colorectal adenomas, whereas those with attenuated polyposis (AAPC) have fewer than 100 adenomas. A further group of individuals, so-called "multiple" adenoma patients, have a phenotype like AAPC, with 3-99 polyps throughout the colorectum, but mostly have no demonstrable germ-line APC mutation. Routine mutation detection techniques fail to detect a pathogenic APC germ-line mutation in approximately 30% of patients with classical polyposis and 90% of those with AAPC/multiple adenomas. We have developed a real-time quantitative multiplex PCR assay to detect APC exon 14 deletions. When this technique was applied to a set of 60 classical polyposis and 143 AAPC/multiple adenoma patients with no apparent APC germ-line mutation, deletions were found exclusively in individuals with classical polyposis (7 of 60, 12%). Fine-mapping of the region suggested that the majority (6 of 7) of these deletions encompassed the entire APC locus, confirming that haploinsufficiency can result in a classical polyposis phenotype. Screening for germ-line deletions in APC mutation-negative individuals with classical polyposis seems warranted.

Adenoma↗
PubMed2001

Preoperative/neoadjuvant medical therapy for early breast cancer.

Preoperative (neoadjuvant) medical therapy has emerged over the past decade as a new approach for the treatment of early breast cancer. Results show it has high activity, but survival is no better than with conventional adjuvant treatment. The need for mastectomy is reduced but not abolished; in some studies this effect is associated with a small increase in risk of local recurrence, but without any detriment to survival. Predictive factors for improved outcome include clinical response, and especially pathological complete remissions. However, persisting pathological axillary node involvement is associated with poor outcome. Biological changes in apoptosis or proliferation pathways may prove to be more sensitive surrogate markers than clinical or pathological responses for assessing treatment outcome. The main long-term aim of preoperative medical treatment must be to establish such surrogate predictive markers. This would lead to individualised treatment for each patient, and would allow much more rapid assessment of new drugs than is currently possible with adjuvant therapy trials.

Breast Neoplasms↗
PubMed2001

Apparent Mendelian inheritance of breast and colorectal cancer: chance, genetic heterogeneity or a new gene?

It is not uncommon for cancer geneticists to be referred families with apparently Mendelian co-inheritance of breast and bowel cancer. Such families present a particular problem as regards the intensity of their screening for these diseases and the utility of genetic testing. Many 'breast-colon' cancer families probably result from chance clustering of two common cancers. Other 'breast-colon' cancer families may result from known cancer syndromes, such as hereditary breast-ovarian cancer or hereditary non-polyposis colon cancer, either by conferring a high risk of one cancer type and a slightly increased risk of the other, or through a predisposition to one of the two cancers and chance occurrence of the other. Anecdotally, however, many geneticists wonder about the existence of a distinct 'breast-colon cancer syndrome', since some families present good a priori evidence of genetic disease and yet cannot readily be accounted for by known genes or chance. The identification of unknown 'breast-colon cancer' genes is likely to be difficult, relying primarily on candidate gene analysis, including loci separately implicated in breast or colorectal cancer, or in other multiple cancer syndromes. Studies such as those on APC I1307K and CHEK2 1100delC may suggest the way forward for the identification of 'breast-colon cancer' genes.

Adult↗
PubMed1993

Cognition-activated low-frequency modulation of light absorption in human brain.

Animal model studies indicate light-absorption changes of the exposed animal brain in response to visual stimulation. Here we report observations of red-light absorbance changes, attributable to repetitive blood concentration changes in response to stimulation in the human brain frontal region by a cognitive process. These responses are observed as low-frequency recurrence of changes by Fourier transform analysis and are attributed to blood concentration change stimulated by the increased metabolic rate of brain tissue in cognitive function. A simple, portable dual wavelength spectrophotometer was attached noninvasively to the human forehead to measure the low frequency and power spectra of fluctuations of absorbances attributed to variations of brain blood concentration in the frontal region. The responses are associated with brain activity in responses to problem solving of analogies presented visually that require an associative function in the frontal region. The method of subtraction of test -rest Fourier transforms minimizes the arterial pulse frequency contributions and identifies specific frequencies--for example, 0.8, 1.6, 1.8 Hz in 24 of 28 tests of nine individuals (85%). Tests in which no increased brain activity was elicited (rest-rest) showed small differences. It is concluded that low-frequency recurrences of brain activity linked to blood concentration increases can be detected in human subjects with an optical device of potentially for simplified tests of cognitive function in the 0- to 3-Hz region and with modifications for wider band recordings in localized tissue volumes by time-resolved spectroscopy.

Adolescent↗