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Biomedical subjects

J D Potter

Publications and source records attributed to J D Potter.

At least 109 records · Page 6Linked to original sources

beta-Carotene and the role of intervention studies.

Vegetables and fruits are associated with a reduced risk of cancers, including especially lung cancer. The possible protective compounds include a wide variety of phytochemicals. However, for historical, technical, and biological reasons, a great deal of attention has focused on a single agent: beta-carotene. Recently, in clinical trials, beta-carotene has been shown not to be an effective agent and, perhaps, to be harmful. Possible explanations for this are presented, as is the danger of reductionist approaches to the explanation of the complex nutrition-related biology of cancer.

Adenomatous Polyps↗

Medical history risk factors for non-Hodgkin's lymphoma in older women.

BACKGROUND: It has been suggested that certain medical conditions and drug exposures might suppress the immune system and increase the risk of developing non-Hodgkin's lymphoma (NHL). PURPOSE: We investigated whether specific medical conditions and drug exposures were associated with the risk of NHL in a cohort of older women who were enrolled in the Iowa Women's Health Study. METHODS: A cohort of 41837 women, 55-69 years of age at baseline, was followed prospectively for the development of cancer from 1986 through 1992. These women had completed a baseline questionnaire in January 1986 that inquired about the occurrence and age at onset of specific medical conditions, about family history of cancer, and about the use of selected medications. Follow-up questionnaires were mailed to the women in 1987, 1989, and 1992. Incident cancers and deaths were ascertained through linkages to state and national databases. For most analyses, women with a self-reported history of cancer at baseline (n = 3903) were excluded. Relative risks (RRs) and 95% confidence intervals (CIs), adjusted for age or for age and other variables, were used as a measure of the association between NHL and medical history factors. Reported P values are two-sided. RESULTS: One hundred fourteen incident cases of NHL were identified in the cohort during follow-up. A history of adult-onset diabetes mellitus (i.e., first diagnosed after the age of 30 years) was associated with an increased risk of developing NHL (age-adjusted RR = 2.18; 95% CI = 1.22-3.90). In addition, there was an association between the duration of adult-onset diabetes and increasing risk of NHL (P for trend = .004), with an age-adjusted RR of 2.90 (95% CI = 1.07-7.90) for women with a diagnosis of diabetes for 15 or more years compared with women with no diagnosis of diabetes. Women with a history of blood transfusion were also at increased risk for the development of NHL (age-adjusted RR = 1.95; 95% CI = 1.33-2.85). The risk estimates for diabetes and transfusion history were independent of each other and were not changed substantially after adjustment for other risk factors. History of a previous cancer (excluding hematopoietic and lymphatic cancers) was associated with an increased risk of NHL (age-adjusted RR = 1.92; 95% CI = 1.21-3.06); this risk estimate was attenuated somewhat after adjustment for a history of diabetes, transfusion history, and other major risk factors (RR = 1.66; 95% CI = 1.02-2.69). No statistically significant associations were found between NHL and a history of chronic colitis, nonestrogen steroid use, use of exogenous estrogens, or use of thyroid medications. CONCLUSIONS AND IMPLICATIONS: A history of adult-onset diabetes mellitus, blood transfusion, and a history of cancer (or its treatment) appear to be independent risk factors for NHL in older women.

Age of Onset↗

Dietary energy sources and colon cancer risk.

Because energy-contributing nutrients are highly correlated with total energy, the association with colon cancer from energy versus other components of energy-providing nutrients is often not clear. Dietary data from a population-based case-control study of colon cancer were analyzed in subjects from California, Utah, and Minnesota in 1991-1994 to assess the colon cancer risk associated with consumption of energy, fat, protein, and carbohydrate. After adjustment for long-term physical activity, total energy intake increased risk of colon cancer in men (odds ratio = 1.74, 95% confidence interval 1.14-2.67 for highest vs. lowest quartile) and in women (odds ratio = 1.70, 95% confidence interval 1.07-2.70). Various methods of analysis suggested that intakes of individual sources of energy (dietary fat, protein, and carbohydrate) were not associated with colon cancer risk after total energy intake was taken into account. People who consumed a high-calorie diet that was dense in fiber and calcium appeared to be at lower risk than people with the same caloric intake who consumed smaller amounts of dietary fiber and calcium. Individuals with a first-degree relative with colorectal cancer, especially those diagnosed at a younger age, were at a greater risk from a diet high in energy than were individuals without a family history of colorectal cancer.

Adult↗

Fluorescent probes attached to Cys 35 or Cys 84 in cardiac troponin C are differentially sensitive to Ca(2+)-dependent events in vitro and in situ.

The goal of the current study was to generate recombinant cTnC proteins with single Cys residues as sites for attachment of fluorescent probes that can distinguish between the structural effects of myosin cross bridges and direct Ca2+ binding to cTnC (cardiac and slow skeletal troponin C) in skinned fibers. We anticipated that cTnC proteins which retain the endogenous Cys 35 (cTnC(C35)) or Cys 84 (cTnC(C84)) would provide fluorescent probes with distinct microenvironments, since these residues are on opposite sides of the globular regulatory domain. In vitro experiments that showed IAANS (2-(4'-(iodoacetamido)anilino)naphthalene-6-sulfonic acid) coupled to Cys 35 can induce unwanted structural perturbations as evidenced by a decreased affinity of site II for Ca2+ when IAANS-labeled cTnC(C35) is bound to cTnI. Important structural features involving Cys 35 in the inactive site I are suggested by a Ca(2+)-dependent increase in reactivity of Cys 35 with sulfhydryl specific reagents when cTnC(C35) is associated with cTnI. These characteristics are not seen for cTnC(C84). When incorporated in situ into skinned cardiac muscle fibers, native cTnC with IAANS bound to both Cys 35 and Cys 84 showed a pCa50 of fluorescence which preceded that of force, while the pCa50 values of both force and fluorescence were coincident for IAANS-labeled cTnC(C84). Disruption of force-producing myosin cross bridges had no effect on the pCa50 of fluorescence for IAANS-labeled cTnC(C84), but induced a rightward shift in the pCa50 of fluorescence for IAANS-labeled native cTnC. These data can be interpreted to indicate that cTnC with IAANS bound to both Cys 35 and C84 senses either myosin cross bridges or direct Ca2+ binding and myosin-induced cooperativity, while IAANS bound to Cys 84 alone senses conformations that are tightly coupled with force generation.

Amino Acid Sequence↗

Tobacco use and colon cancer.

Smoking cigarettes has been consistently associated with adenomatous polyps. However, only a few studies have reported associations between smoking cigarettes or using other forms of tobacco and colon cancer. A population-based case-control study of colon cancer was conducted in 3 areas in the United States: northern California, Utah and Minnesota. We observed approximately a 50% increase in colon cancer risk from smoking over a pack of cigarettes per day among both men and women. Those who stopped smoking remained at increased risk, even if they stopped over 10 years ago. Our data suggest that the amount smoked may be a more important factor than the total number of years smoked. Smoking neither cigars nor pipes was associated with an increased risk of colon cancer. Among female participants only, those who smoked over 20 cigarettes per day and had a large body mass index were at greater risk of colon cancer than participants who smoked the same amount but were smaller (p for interaction among women = 0.04).

Adolescent↗

Physical activity and colon cancer: a public health perspective.

PURPOSE: It has been suggested that performing physical activity for at least 30 min on most days of the week will improve health. The purpose of this study was to assess the association between physical activity and colon cancer as it relates to this public health recommendation. METHODS: A large population-based case-control study of colon cancer was conducted. Study participants came from three areas of the United States: Northern California, Utah, and the Twin Cities Metropolitan Area in Minnesota. RESULTS: Long-term involvement in high levels of activity, equivalent to > or = 60 min of vigorous activity per session, was associated with decreased risk (odds ration [OR], 0.68; 95% confidence interval [CI] 0.52-0.87). The amount of time involved in the activity appeared to have a greater impact than the number of days per week that activities were performed. Those reporting the highest level of activity, as defined by both duration and vigorous intensity, were at the lowest risk (OR, 0.62; 95% CI, 0.52-0.75) relative to those who were sedentary; associations did not differ by age at diagnosis, site of the tumor within the colon, or sex. The inverse association between colon cancer and long-term vigorous leisure-time activity was slightly stronger among those without a family history of colorectal cancer than among those with a family history of colorectal cancer. From these data we estimate that 13% of colon cancer could be attributed to lack of vigorous leisure-time activity in the population; we estimate that 4.3 cases of colon cancer/100,000 population are prevented each year because people are involved in vigorous leisure-time physical activity. CONCLUSIONS: Data from this study suggest that a high level of vigorous leisure-time activity performed over the past 20 years was important in reducing colon cancer risk; the greatest inverse association was observed when activities were performed for longer periods of time per session for the past 20 years. These and other data indicate that it is important to identify ways to facilitate an increase in leisure-time physical activity within the population.

Adult↗

Evaluating the relationships among maternal reproductive history, birth characteristics, and infant leukemia: a report from the Children's Cancer Group.

PURPOSE: Specific events in the mother's reproductive history and certain birth characteristics have been associated with childhood leukemia. Few studies have explored these associations specifically in infants. METHODS: The Children's Cancer Group (CCG) conducted three separate case-control studies of childhood leukemia that involved similar methodologies and data collection. Data from interviews of the mothers of a total of 303 children diagnosed with leukemia at 1 year of age or younger and their matched controls (n = 468) were available from the three studies. These data included maternal reproductive history (stillbirths, abortions, and miscarriages) and certain birth characteristics of the index child. RESULTS: Compared with controls, cases were significantly more likely to be female (P < 0.01) and were more often heavier at birth (particularly cases diagnosed after 6 months of age (odds ratio, 4.18; 95% confidence interval, 1.75-10.02)). Overall, there were no statistically significant differences between cases and controls in regard to maternal report of any type of previous fetal loss. Finally, being a later-born child was associated with an increased risk of acute myeloid leukemia but not of acute lymphoblastic leukemia. CONCLUSIONS: The relationships among birthweight, prior fetal loss, and risk of infant leukemia appear to be complex. Further studies of infant leukemia that incorporate molecular as well as epidemiologic data may help to elucidate these differences.

Adolescent↗

Performance of a shortened telephone-administered version of a quantitative food frequency questionnaire.

PURPOSE: We evaluated the performance of a telephone-administered food frequency questionnaire in a study of 190 men and women, 30-79 years of age, who participated as controls in a study of colon cancer. METHODS: The telephone version of the questionnaire was modified from a longer food frequency questionnaire originally administered in person to each of the participants. One month later, the telephone questionnaire was administered to a subgroup of 190 participants and readministered to 169 members of the subgroup two weeks later to assess the reproducibility and comparative validity of the instrument. RESULTS: The unadjusted correlation for energy between the original in-person full food frequency questionnaire and the abbreviated telephone version was 0.69. The median energy intake from the telephone version was 17% lower in men and 23% lower in women. The energy and sex-adjusted correlation coefficients for other nutrients ranged from 0.45 for vitamin E to 0.78 for fiber. The intraclass correlation coefficients to measure reproducibility ranged from 0.62 for animal protein to 0.83 for folate. CONCLUSIONS: These data indicate that this brief, telephone-administered questionnaire is reproducible and provides a ranking of nutrient intake comparable to that provided by a full in-person interview.

Adult↗

Seasonal trends in the self-detection of breast cancer: indications from the Cancer and Steroid Hormone (CASH) study.

Of 2895 women who self-detected an incident breast cancer that required surgery, peaks in month of detection occurred in spring and late autumn (p = 0.012). For the subset of cases for whom receptor status was available, there was a highly significant seasonal variation in detection only for those with ER-negative tumors. Further investigations into seasonality and breast cancer detection may be warranted.

Adult↗

Vitamin supplements and cancer risk: the epidemiologic evidence.

This report reviews published epidemiologic research on the associations of vitamin and mineral supplementation with cancer risk. Although the literature on nutrition and cancer is vast, few reports to date have addressed supplemental nutrients directly (seven clinical trials, 16 cohort, and 36 case-control studies). These studies offer insight into effects of nutrients that are distinguishable from effects of other biologically active compounds in foods. Randomized clinical trials have not shown significant protective effects of beta-carotene, but have found protective effects of: alpha-tocopherol against prostate cancer; mixtures of retinol/zinc and beta-carotene/alpha-tocopherol/selenium against stomach cancer; and selenium against total, lung, and prostate cancers. Cohort studies provide little evidence that vitamin supplements are associated with cancer. Case-control studies have reported an inverse association between bladder cancer and vitamin C; oral/pharyngeal cancer and several supplemental vitamins; and several cancers and vitamin E. A randomized clinical trial, a cohort study, and a case-control study have all found inverse associations between colon cancer and vitamin E. Overall, there is modest evidence for protective effects of nutrients from supplements against several cancers. Future studies of supplement use and cancer appear warranted; however, methodologic problems that impair ability to assess supplement use and statistical modeling of the relation between cancer risk and supplement use need attention.

Case-Control Studies↗

Hormone replacement therapy, reproductive history, and colon cancer: a multicenter, case-control study in the United States.

Hormonal factors have been inconsistently associated with colon cancer risk in women. The associations between reproductive events, menstrual factors, exogenous hormones, and colon cancer were evaluated in a large case-control study (894 female cases and 1,120 female age-matched population-based controls) in the United States, stratifying by age at diagnosis, tumor site, family history and other potential risk factors. Overall, higher parity was associated with a marginally decreased risk of colon cancer (five or more births compared with nulliparous: odds ratio [OR] = 0.75, 95 percent confidence interval [CI] = 0.53-1.06) after adjusting for age at diagnosis, family history of colorectal cancer, vigorous lifetime physical activity, body mass index (BMI) (wt/ht1.5), total energy intake, and aspirin use. No important associations were observed for other reproductive or menstrual events. An inverse association between recent use of hormone replacement therapy (HRT) and colon cancer was observed (OR = 0.71, CI = 0.56-0.89). Although interaction terms were not significant, this inverse association appeared to be more pronounced for those with an older age at diagnosis; for those without a first-degree relative with colorectal cancer; and for those with a relatively low BMI. The reduced risk associated with HRT use did not appear to be explained by other behaviors related to HRT use.

Adult↗

The relationship between dietary fat intake and risk of colorectal cancer: evidence from the combined analysis of 13 case-control studies.

The objective of this study was to examine the effects of the intake of dietary fat upon colorectal cancer risk in a combined analysis of data from 13 case-control studies previously conducted in populations with differing colorectal cancer rates and dietary practices. Original data records for 5,287 cases of colorectal cancer and 10,470 controls were combined. Logistic regression analysis was used to estimate odds ratios (OR) for intakes of total energy, total fat and its components, and cholesterol. Positive associations with energy intake were observed for 11 of the 13 studies. However, there was little, if any, evidence of any energy-independent effect of either total fat with ORs of 1.00, 0.95, 1.01, 1.02, and 0.92 for quintiles of residuals of total fat intake (P trend = 0.67) or for saturated fat with ORs of 1.00, 1.08, 1.06, 1.21, and 1.06 (P trend = 0.39). The analysis suggests that, among these case-control studies, there is no energy-independent association between dietary fat intake and risk of colorectal cancer. It also suggests that simple substitution of fat by other sources of calories is unlikely to reduce meaningfully the risk of colorectal cancer.

Adult↗

Plant foods and colon cancer: an assessment of specific foods and their related nutrients (United States).

Plant foods have been associated inversely with colon cancer. Since a major focus of this study was to identify components of plant foods which may account for their association with colon cancer, nutrients which are commonly found in plant foods also were evaluated. A population-based case-control study was conducted in Northern California, Utah, and the 'Twin Cities' area of Minnesota (United States). Complete data were available from interviewer-administered questionnaires on 1,993 cases and 2,410 controls. Higher intakes of vegetables (for highest relative to lowest quintile of intake) were associated inversely with colon cancer risk: the odds ratio (OR) was 0.7 for both men (95 percent [CI] confidence interval = 0.5-0.9) and women (CI = 0.5-1.0). Associations were stronger among those with proximal tumors. Total fruit intake was not associated with colon cancer risk although, among men, higher levels of whole grain intake were associated with a decreased risk (OR = 0.6, CI = 0.4-0.9 for older men); high intakes of refined grains were associated with an increased risk (OR = 1.5, CI = 1.1-2.1). Dietary fiber intake was associated with a decreased risk of colon cancer: OR = 0.5 (CI = 0.3-0.9) for older men; OR = 0.7 (CI = 0.4-1.2) for older women; OR = 0.6 (CI = 0.4-1.0) for men with proximal tumors; OR = 0.5 (CI = 0.3-0.9) for women with proximal tumors. Other nutrients, for which plant foods were the major contributor--such as vitamin B6, thiamin, and niacin (women only)--also were associated inversely with colon cancer. Neither beta-carotene nor vitamin C was protective for colon cancer. Adjustment of plant foods for nutrients found in plant foods or for supplement use did not appreciably alter the observed associations between plant foods and colon cancer.

Adult↗

The effect of pH on the Ca2+ affinity of the Ca2+ regulatory sites of skeletal and cardiac troponin C in skinned muscle fibres.

It is known that intracellular pH drops rapidly after the onset of ischemia in cardiac muscle and may play some role in the rapid drop in force that ensues. It is also known that alpha 1-adrenoceptor agonists alkalinize intracellular pH by stimulating Na+/H+ exchange and may represent a mechanism which facilitates recovery of intracellular pH from acidosis. Lowering or raising pH shifts the Ca2+ dependence of force development in muscle fibres to higher or lower free Ca2+ concentrations, respectively, yet the precise mechanism is unknown. To investigate this phenomenon we have used skinned skeletal or cardiac muscle fibres whose endogenous troponin C (TnC) has been replaced with chicken skeletal TnC labelled with DANZ (STnCDANZ) or recombinant cardiac TnC labelled with IAANS (CTnC3(C84)[AANS), respectively. The fluorescence of the STnCDANZ or CTnC3(C84)IAANS was enhanced by Ca2+ binding to the Ca(2+)-specific (regulatory) site(s) of STnC or CTnC when incorporated into skinned fibres, and was measured simultaneously with force. When the pH was changed from 7.0 to 6.5 or 7.5 the shift in the Ca2+ dependence of force paralleled the shift in fluorescence. Since the force and fluorescence shift in parallel as the pH is lowered or raised, it can be concluded that these changes in Ca2+ sensitivity are caused by a decrease or increase, respectively, in the Ca2+ affinity of the Ca(2+)-specific site(s) of TnC. Since lowering or raising the pH also resulted in lower or higher, respectively, maximal Ca2+ activated force while maximal fluorescence remained unchanged, it is possible that H+ may act indirectly, as well, by reducing or increasing, respectively, the number or type of crossbridges attached to actin and thereby alter the crossbridge induced depression or elevation, respectively of the observed TnC Ca2+ affinity. Experiments with 2,3-butanedione monoxime, however, where force-generating crossbridges were greatly reduced, indicated that the pH effect may be primarily related to a direct change in the Ca2+ affinity to the regulatory sites of TnC.

Amino Acid Substitution↗

Helicobacter pylori--in vitro susceptibility to garlic (Allium sativum) extract.

Gastric cancer is the major cancer in the developing world and one of the top two worldwide. Helicobacter pylori is a bacterium implicated in the etiology of stomach cancer. The incidence of stomach cancer is lower in individuals and populations with high Allium vegetable intakes. Allium vegetables, particularly garlic, have antibiotic activity. Standard antibiotic regimens against H. pylori are frequently ineffective in high-risk populations. As part of our study of the role of Allium vegetable intake on cancer prevention, we wished to investigate its antimicrobial activity against H. pylori. An aqueous extract of garlic cloves was standardized for its thiosulfinate concentration and tested for its antimicrobial activity on H. pylori grown on chocolate agar plates. Minimum inhibitory concentration was 40 micrograms thiosulfinate per milliliter. Staphylococcus aureus tested under the same conditions was not susceptible to garlic extract up to the maximum thiosulfinate concentration tested (160 micrograms/ml). To our knowledge, this is the first report of H. pylori's susceptibility to garlic extract of known thiosulfinate concentration. It is plausible that the sensitivity of H. pylori to garlic extract at such low concentration may be related to the reported lower risk of stomach cancer in those with a high Allium vegetable intake. Furthermore, it may identify a strategy for a low-cost intervention, with few side effects, in populations at high risk for stomach cancer, particularly where antibiotic resistance and the risk of reinfection are high.

Anti-Bacterial Agents↗

Are dietary factors involved in DNA methylation associated with colon cancer?

Disturbances in DNA methylation have been hypothesized as being involved in carcinogenesis. It has been proposed that dietary factors such as folate, alcohol, and methionine may be associated with colon cancer because of their involvement in DNA methylation processes. Data from a large retrospective population-based case-control study of incident colon cancer were used to evaluate whether intake of alcohol and other dietary factors involved in DNA methylation are associated with colon cancer. Dietary data were obtained using a detailed diet history questionnaire. We did not observe strong independent associations between folate, vitamin B6, vitamin B12, methionine, or alcohol and risk of colon cancer after adjusting for body size, physical activity, cigarette smoking patterns, energy intake, and dietary intake of fiber and calcium. However, when assessing the associations between colon cancer and a composite dietary profile based on alcohol intake, methionine, folate, vitamin B12, and vitamin B6, we observed a trend of increasing risk as one moved from a low- to a high-risk group. This trend was modest and most marked in those diagnosed at a younger age [odds ratio (OR) for men = 1.3, 95% confidence interval (CI) = 0.9-1.9; OR for women = 1.6, 95% CI = 1.0-2.6]. We observed that associations with this high-risk dietary profile were greater among those who took aspirin or nonsteroidal anti-inflammatory drugs on a regular basis and were younger at the time of diagnosis (men OR = 1.7, 95% CI = 1.0-3.2; women OR = 2.2, 95% CI = 1.0-4.8) and for distal tumors (men OR = 1.4, 95% CI = 0.9-2.3; women OR = 2.0, 95% CI = 1.0-3.8). Findings from this study provide only limited support for previously reported associations between dietary factors involved in DNA methylation and risk of colon cancer.

Aged↗

Metabolic activation of aromatic amines by human pancreas.

Epidemiologic studies have suggested that aromatic amines (and nitroaromatic hydrocarbons) may be carcinogenic for human pancreas. Pancreatic tissues from 29 organ donors (13 smokers, 16 non-smokers) were examined for their ability to metabolize aromatic amines and other carcinogens. Microsomes showed no activity for cytochrome P450 (P450) 1A2-dependent N-oxidation of 4-aminobiphenyl (ABP) or for the following activities (and associated P450s): aminopyrine N-demethylation and ethylmorphine N-demethylation (P450 3A4); ethoxyresorufin O-deethylation (P450 1A1) and pentoxyresorufin O-dealkylation (P450 2B6); p-nitrophenol hydroxylation and N-nitrosodimethyl-amine N-demethylation (P450 2E1); lauric acid omega-hydroxylation (P450 4A1); and 4-(methylnitrosamino)-1-(3-pyridyl-1-butanol) (NNAL) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) alpha-oxidation (P450 1A2, 2A6, 2D6). Antibodies were used to examine microsomal levels of P450 1A2, 2A6, 2C8/9/18/19, 2E1, 2D6, and 3A3/4/5/7 and epoxide hydrolase. Immunoblots detected only epoxide hydrolase at low levels; P450 levels were <1% of liver. Microsomal benzidine/prostaglandin hydroperoxidation activity was low. In pancreatic cytosols and microsomes, 4-nitrobiphenyl reductase activities were present at levels comparable to human liver. The O-acetyltransferase activity (AcCoA-dependent DNA-binding of [3H]N-hydroxy-ABP) of pancreatic cytosols was high, about twothirds the levels measured in human colon. Cytosols showed high activity for N-acetylation of p-aminobenzoic acid, but not of sulfamethazine, indicating that acetyltransferase-1 (NAT1) is predominantly expressed in this tissue. Cytosolic sulfotransferase was detected at low levels. Using 32P-post-labeling enhanced by butanol extraction, putative arylamine-DNA adducts were detected in most samples. Moreover, in eight of 29 DNA samples, a major adduct was observed that was chromatographically identical to the predominant ABP-DNA adduct, N-(deoxyguanosin-8-yl)-ABP. These results are consistent with a hypothesis that aromatic amines and nitroaromatic hydrocarbons may be involved in the etiology of human pancreatic cancer.

Acetyltransferases↗