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W Cohn

Publications and source records attributed to W Cohn.

14 recordsLinked to original sources
PubMed2001

Knowledge about breast cancer risk factors and hereditary breast cancer among early-onset breast cancer survivors.

Little is known about knowledge levels regarding hereditary breast cancer among breast cancer survivors. This study explored, among women with early-onset breast cancer (<50 years): 1) knowledge regarding breast cancer risk factors and hereditary breast cancer; and 2) differences in knowledge based on risk for hereditary disease. Participants recruited from 34 Virginia hospitals responded to two questionnaires. The Family History Questionnaire assessed risk for hereditary breast cancer. The Knowledge, Attitudes, and Beliefs Questionnaire evaluated knowledge of general breast cancer risk factors and hereditary breast cancer. Of 314 respondents, 273 (87%) returned both questionnaires. A total of 137 (52%) participants met the study's criteria for hereditary breast cancer risk. Most participants knew common breast cancer-associated risk factors, including family history of breast cancer. Only 35% recognized family history of non-breast malignancies as a risk factor for breast cancer. Most participants recognized that prophylactic mastectomy does not eliminate breast cancer risk (63%), that not all women carrying a mutation develop disease (73%), and that men can develop breast cancer (96%). The majority selected 'I don't know' for knowledge of several characteristics of hereditary breast cancer, including: early-onset disease (54%); multifocal or bilateral disease (62%); risk transmission through fathers (58%); association with other cancer types (61%); and male breast cancer (70%). Knowledge regarding hereditary breast cancer did not vary between women with suspected hereditary disease and those with presumed sporadic disease. These data highlight the need for information regarding hereditary breast cancer for early-onset breast cancer survivors.

Age of Onset↗
PubMed2001

Factors predictive of difficult colonoscopy.

BACKGROUND: Prediction of a technically difficult colonoscopy may influence patient selection and procedure scheduling. Identification of predictive factors may be difficult because a common endpoint used to evaluate the success of colonoscopy is intubation of the cecum, which is usually achieved. The goal of this study was to examine the feasibility of using an alternative measure, time required for cecal intubation, to identify factors that can impact performance of colonoscopy. METHODS: The time required for cecal intubation was prospectively recorded for 802 consecutive outpatient colonoscopies performed by 7 experienced gastroenterologists. Patient data collected included height, weight, age, bowel habits, surgical history, and findings at colonoscopy. Forty-seven examinations that were stopped because of disease or unacceptable bowel preparation were excluded. The impact of the patient characteristics of the remaining sample of 755 patients on the median time required for cecal intubation for men and women was examined. RESULTS: Older age and female gender, body mass index < or =25.0 (regardless of gender), diverticular disease in women, and a history of constipation or reported laxative use in men were predictors of difficult colonoscopy. CONCLUSIONS: By using median time required for cecal intubation, several patient characteristics were identified that may predict technical difficulty at colonoscopy. These findings have implications for practice and teaching.

Age Factors↗
PubMed2000

Men's attitudes regarding genetic testing for hereditary prostate cancer risk.

OBJECTIVES: Little is known about the attitudes of men unselected for a family history for prostate cancer concerning genetic testing for prostate cancer risk or genetic testing for inherited cancer predisposition. To explore this, we examined the interest in molecular testing for hereditary prostate cancer (HPC) predisposition among a self-selected cohort of 342 men presenting for prostate cancer screening. METHODS: Participants were surveyed concerning their attitudes about DNA testing for HPC predisposition and knowledge of prostate cancer-associated risk factors, including heredity. RESULTS: Of the participants completing the survey, 92% expressed interest in learning about DNA testing, and 89% stated that they would undergo DNA analysis for HPC predisposition, if available. Twenty-eight percent of respondents failed to demonstrate an adequate understanding of the concept of "inherited tendency." The demonstrated level of understanding of this concept did not differ by the respondent's family history, although it varied by race. An interest in learning about or undergoing testing did not vary by race, family history, or demonstrated understanding of the concept of inherited risk. CONCLUSIONS: Among men presenting for routine prostate cancer screening, interest in learning about testing for HPC predisposition and in having such testing performed may be high. The data also provide evidence that, in a population of men unselected for family history, interest in molecular testing for this common, male-specific cancer may parallel the high interest level demonstrated among women in DNA testing for inherited breast and ovarian cancer risk.

Adult↗
PubMed1992

Plasma clearance and net uptake of alpha-tocopherol and low-density lipoprotein by tissues in WHHL and control rabbits.

The mechanism(s) of uptake of vitamin E (alpha-tocopherol) by tissues is poorly understood. It has, however, been suggested from studies in vitro that the apolipoprotein B/E (apo B/E) receptor pathway for low-density lipoprotein (LDL) may be involved. To investigate the role of the apo B/E receptor pathway in vivo, we have studied the transport and uptake of alpha-tocopherol by tissues in Watanabe Heritable Hyperlipidaemic (WHHL) rabbits, which lack functional LDL (apo B/E) receptors, and controls. [3H]alpha-Tocopherol incorporated within LDL labelled with [14C]sucrose was used in these studies, as this enabled the uptake of both alpha-tocopherol and LDL to be studied independently. The principal findings were as follows. (1) Concentrations of the circulating lipids (including alpha-tocopherol) and LDL were increased and the plasma fractional disappearance rates of alpha-tocopherol and LDL decreased in the WHHL rabbits. (2) The WHHL rabbits clear more LDL and alpha-tocopherol from the circulation than controls do, because of their increased pool sizes of alpha-tocopherol and LDL. (3) The lipoprotein composition of the WHHL rabbits differed from that of the controls, and there was exchange of alpha-tocopherol between the lipoprotein fractions in vivo and in vitro. (4) High-affinity apo B/E receptors were not essential for the uptake of alpha-tocopherol by tissues. (5) Evidence from the plasma-clearance and tissue data suggest that alpha-tocopherol can be taken up by tissues in association with, and also independent of, LDL. We conclude that there are several different mechanisms for the uptake of alpha-tocopherol by tissues, which include receptor-dependent and receptor-independent pathways, independent transport and co-transport of alpha-tocopherol and LDL, and uptake from a number of different lipoproteins.

Animals↗
PubMed1989

The role of the low density lipoprotein receptor for alpha-tocopherol delivery to tissues.

To study the role of the LDL receptor pathway for the maintenance of alpha-tocopherol concentrations in tissues of intact animals, we have compared vitamin E levels in plasma and tissues of normal rabbits and WHHL rabbits. WHHL rabbits are deficient in LDL receptor activity. For WHHL rabbits, alpha-tocopherol plasma concentrations were elevated to 10 times normal levels. When plasma lipoprotein profiles were analyzed by density gradient centrifugation, concentrations of VLDL, IDL, and LDL were increased in WHHL rabbits, and plasma alpha-tocopherol was only recovered in these fractions. In normal rabbits, plasma alpha-tocopherol was confined mainly to the HDL fraction; levels associated with LDL were markedly lower. Despite LDL receptor deficiency, alpha-tocopherol concentrations in various tissues of WHHL rabbits were not found to be reduced, with the exception of the adrenal. Vitamin E levels in muscle and kidney of WHHL rabbits exceeded those of normal animals. Our results demonstrate the importance of the LDL receptor pathway for vitamin E clearance in the normal rabbit, although at high LDL concentrations, alternative mechanisms may become more efficient for the delivery of vitamin E to tissues.

Adrenal Glands↗
PubMed1988

Alpha-tocopherol is secreted from rat liver in very low density lipoproteins.

Three separate studies were carried out to test the hypothesis that rat liver secretes vitamin E (alpha-tocopherol) within very low density lipoproteins (VLDL). i) When the clearance of plasma chylomicrons (CM) and VLDL was blocked by the administration of Triton WR-1339, alpha-tocopherol concentrations increased linearly with time in both classes of triacylglycerol-rich lipoproteins, although accumulation rates within VLDL exceeded those within CM. For fasted rats, appearance of alpha-tocopherol in VLDL persisted at slightly reduced rates. alpha-Tocopherol and triglycerides in the VLDL fraction responded to Triton WR-1339 administration by coordinate increases. In contrast to the situation in serum, alpha-tocopherol concentrations decreased in the liver following injection of Triton. ii) In order to inhibit the secretion of hepatic lipoproteins containing apolipoprotein B (apoB), rats were fed a diet containing orotic acid. This resulted in a reduction of apoB and alpha-tocopherol concentrations in serum and VLDL, whereas the vitamin E content of liver was increased. iii) In primary cultures of hepatocytes, alpha-tocopherol was secreted into the culture media predominantly within VLDL. We, therefore, conclude that the liver secretes alpha-tocopherol within VLDL and in this way contributes to the maintenance of serum vitamin E concentrations.

Animals↗
PubMed1979

N-(5-Phosphoribosyl)anthranilate isomerase-indoleglycerol-phosphate synthase. 2. Fast-reaction studies show that a fluorescent substrate analogue binds independently to two different sites.

The mechanism of binding of reduced 1-(2-carboxyphenylamino)-1-deoxyribulose 5-phosphate (rCdRP) to two different binding sites on the bifunctional enzyme is determined by kinetic studies, using temperature-jump and stopped-flow equipment with fluorescence detection. Two rapid binding processes and a comparatively slow isomerization process are observed over a wide range of enzyme and rCdRP concentrations. Kinetic measurements with low concentrations of rCdRP show that the isomerization is coupled only to the more rapid of the two binding reactions that involves the active site of indoleglycerol-phosphate synthase. The slower of the two binding reactions represents rCdRP binding in one step to the active site of (phosphoribosyl)anthranilate isomerase. The simplest mechanism explaining quantitatively the dependence of the relaxation times on concentration consists of rCdRP binding to two sites on the enzyme that are intrinsically different and independent, even to the extent that a ligand-induced isomerization of one site is not transmitted to the other site. Simulation studies show that the concentration dependences of the amplitudes of the three relaxation processes are also consistent with the mechanism. The results are discussed in terms of two autonomous domains of folding of the polypeptide chain.

Carboxy-Lyases↗
PubMed1976

Regulation of enzyme synthesis in the tryptophan pathway of Acinetobacter calcoaceticus.

In Acinetobacter calcoaceticus the seven genes coding for the enzymes responsible for tryptophan synthesis map at three chromosomal locations. Two three-gene clusters, one (trpGDC) specifying the small subunit of anthranilate synthase, phosphoribosyl transferase, and indoleglycerol phosphate synthase and the other (trpFBA) specifying phosphoribosyl anthranilate isomerase and both tryptophan synthase subunits, are not linked to each other or to the trpE gene specifying the large anthranilate synthase subunit. When regulation of trp gene expression is studied in the wild type, only the level of the trpF gene product decreases upon addition of tryptophan to the medium. Tryptophan starvation of tryptophan auxotrophs, however, results in increased levels of all the tryptophan enzymes; this and additional evidence suggests that the expression of all the trp genes is subject to repression. The trpGDC genes are coordinately controlled, and the trpE gene is regulated in parallel with them. The trpFBA genes are controlled neither coordinately nor in parallel with the other trp genes, but respond proportionally when compared with each other. So far, two types of constitutive mutants have been found. The first class of mutants apparently occurs in the structural gene for a repressor protein; this repressor locus is unlinked to any of the biosynthetic trp genes and affects only the expression of trpE and the trpGDC cluster. The second class contains mutants closely linked to the trpGDC region; they overproduce only the gene products of this cluster.

Acinetobacter↗