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Biomedical subjects

M L McCullough

Publications and source records attributed to M L McCullough.

At least 19 recordsLinked to original sources
PubMed2001

Vitamin C and vitamin E supplement use and colorectal cancer mortality in a large American Cancer Society cohort.

Some recent epidemiological studies have suggested that use of vitamin C or vitamin E supplements, both of which are important antioxidants, may substantially reduce the risk of colon or colorectal cancer. We examined the association between colorectal cancer mortality and use of individual vitamin C and E supplements in the American Cancer Society's Cancer Prevention Study II cohort. We used proportional hazards modeling to estimate rate ratios among 711,891 men and women in the United States who completed a self-administered questionnaire at study enrollment in 1982, had no history of cancer, and were followed for mortality through 1996. During the 14 years of follow-up, 4404 deaths from colorectal cancer occurred. After adjustment for multiple colorectal cancer risk factors, regular use of vitamin C or E supplements, even long-term use, was not associated with colorectal cancer mortality. The combined-sex rate ratios were 0.89 [95% confidence interval (CI), 0.73-1.09] for 10 or more years of vitamin C use and 1.08 (95% CI, 0.85-1.38) for 10 or more years of vitamin E use. In subgroup analyses, use of vitamin C supplements for 10 or more years was associated with decreased risk of colorectal cancer mortality before age 65 years (rate ratio = 0.48; 95% CI, 0.28-0.81) and decreased risk of rectal cancer mortality at any age (rate ratio = 0.40; 95% CI, 0.20-0.80). Our results do not support a substantial effect of vitamin C or E supplement use on overall colorectal cancer mortality.

Adult↗
PubMed2000

Adherence to the Dietary Guidelines for Americans and risk of major chronic disease in women.

BACKGROUND: Little is known about the overall health effects of adherence to the Dietary Guidelines for Americans. The healthy eating index (HEI), developed at the US Department of Agriculture, measures how well Americans' diets conform to these guidelines. OBJECTIVE: We tested whether the HEI (scores range from 0 to 100; 100 is best) calculated from food-frequency questionnaires (HEI-f) would predict risk of major chronic disease in women. DESIGN: A total of 67272 US female nurses who were free of major disease completed detailed questionnaires on diet and chronic disease risk factors in 1984 and repeatedly over 12 y. Major chronic disease was defined as fatal or nonfatal cardiovascular disease (myocardial infarction or stroke, n = 1365), fatal or nonfatal cancer (n = 5216), or other nontraumatic deaths (n = 496), whichever came first. We also examined cardiovascular disease and cancer as separate outcomes. RESULTS: After adjustment for smoking and other risk factors, the HEI-f score was not associated with risk of overall major chronic disease in women [relative risk (RR) = 0.97; 95% CI: 0.89, 1.06 comparing the highest with the lowest quintile of HEI-f score]. Being in the highest HEI-f quintile was associated with a 14% reduction in cardiovascular disease risk (RR = 0.86; 95% CI: 0.72, 1. 03) and was not associated with lower cancer risk (RR = 1.02; 95% CI: 0.93, 1.12). CONCLUSION: These data suggest that adherence to the 1995 Dietary Guidelines for Americans, as measured by the HEI-f, will have limited benefit in preventing major chronic disease in women.

Adult↗
PubMed2000

Adherence to the Dietary Guidelines for Americans and risk of major chronic disease in men.

BACKGROUND: The Dietary Guidelines for Americans and the food guide pyramid aim to reduce the risk of major chronic disease in the United States, but data supporting their overall effectiveness are sparse. The healthy eating index (HEI) measures the concordance of dietary patterns with these guidelines. OBJECTIVE: We tested whether a high HEI score (range: 0-100; 100 is best) calculated from a validated food-frequency questionnaire (HEI-f) could predict lower risk of major chronic disease in men. DESIGN: A cohort of US male health professionals without major disease completed detailed questionnaires on food intake and other risk factors for heart disease and cancer in 1986 and repeatedly during the 8-y follow-up. Major chronic disease outcome was defined as incident major cardiovascular disease (stroke or myocardial infarction, n = 1092), cancer (n = 1661), or other non-trauma-related deaths (n = 366). RESULTS: The HEI-f was weakly inversely associated with risk of major chronic disease [comparing highest with lowest quintile of the HEI-f, relative risk (RR) = 0.89; 95% CI: 0.79, 1.00; P: < 0.001 for trend]. The HEI-f was associated with moderately lower risk of cardiovascular disease (RR = 0.72; 95% CI: 0.60, 0.88; P: < 0.001) but was not associated with lower cancer risk. CONCLUSIONS: The HEI-f was only weakly associated with risk of major chronic disease, suggesting that improvements to the HEI may be warranted. Further research on the HEI could have implications for refinements to the Dietary Guidelines for Americans and the food guide pyramid.

Alcohol Drinking↗
PubMed1999

Descriptive characteristics of the dietary patterns used in the Dietary Approaches to Stop Hypertension Trial. DASH Collaborative Research Group.

The Dietary Approaches to Stop Hypertension trial was a randomized, multicenter, controlled feeding study to compare the effect on blood pressure of 3 dietary patterns: control, fruits and vegetables, and combination diets. The patterns differed in selected nutrients hypothesized to alter blood pressure. This article examines the food-group structure and nutrient composition of the study diets and reports participant nutrient consumption during intervention. Participants consumed the control dietary pattern during a 3-week run-in period. They were then randomized either to continue on the control diet or to change to the fruits and vegetables or the combination diet for 8 weeks. Sodium intake and body weight were constant during the entire feeding period. Analysis of variance models compared the nutrient content of the 3 diets. Targeting a few nutrients thought to influence blood pressure resulted in diets that were profoundly different in their food-group and nutrient composition. The control and fruits and vegetables diets contained more oils, table fats, salad dressings, and red meats and were higher in saturated fat, total fat, and cholesterol than was the combination diet. The fruits and vegetables and combination diets contained relatively more servings of fruits, juices, vegetables, and nuts/seeds, and were higher in magnesium, potassium, and fiber than was the control diet. Both the fruits and vegetables and combination diets were low in sweets and sugar-containing drinks. The combination diet contained a greater variety of fruits, and its high calcium content was obtained by increasing low-fat dairy products. In addition, the distinct food grouping pattern across the 3 diets resulted in substantial differences in the levels of vitamins A, C, E, folate, B-6, and zinc.

Adult↗
PubMed1999

Pre-enrollment diets of Dietary Approaches to Stop Hypertension trial participants. DASH Collaborative Research Group.

A large body of evidence suggests that several nutrients are related to blood pressure. Less is known about the eating patterns of special populations, such as those at risk for hypertension, or how demographic factors affect the diets of these populations. This article characterizes the usual diets of participants before they enrolled in the Dietary Approaches to Stop Hypertension (DASH) trial. During screening for DASH, 380 participants completed the National Cancer Institute food frequency questionnaire. Nutrient and food group intake, the Keys score (a measure of a diet's atherogenicity), and the Diet Quality Index were estimated from the food frequency questionnaire. The effects of age, sex, race, baseline weight, and education on these dietary factors were assessed among DASH participants and compared with similar data from the Third National Health and Nutrition Examination Survey and other published reports. Among DASH participants, African-Americans reported lower intakes of dairy products (P < .001), calcium (P < .001), and magnesium (P < .05) than did whites. Older women reported greater intakes of calcium, magnesium, and potassium (all P < .05) and less fat (P < .05) than did younger women. Older men consumed fewer servings of fruits (P < .03), less vitamin C (P < .05), and had a higher Keys score (P < .05) than did younger men. Heavier (body mass index > or = 25) participants reported lower intakes of protein and potassium, but higher fat and energy intakes (all P < .05). Taken together, these data show that younger, overweight African-American women have the least healthful diets, because they consume more atherogenic foods and fewer of the nutrients related to decreased blood pressure. Overall Diet Quality Index scores did not differ between African-American and white participants. Despite differences in dietary assessment methods between the population samples of DASH and the Third National Health and Nutrition Examination Survey, within each population sample patterns of micronutrient intake were similar between African-American and white participants.

Adult↗
PubMed1999

The Linear Index Model for establishing nutrient goals in the Dietary Approaches to Stop Hypertension trial. DASH Collaborative Research Group.

Establishing target levels of nutrients in feeding studies presents a challenge to dietitians. Although researchers studying energy-containing nutrients, such as protein and fat, commonly establish target levels according to body weight or as a percentage of energy, it is less clear how to establish levels of micronutrients. Typically, a constant target level is used regardless of energy requirements. Alternatively, nutrients could be provided at a fixed level per 1,000 kcal. Such an approach, however, could result in absolute levels of nutrient intakes that are difficult to achieve through foods alone, particularly for persons with high energy requirements. This report describes the Linear Index Model, a new approach for establishing target levels of selected micronutrients in the Dietary Approaches to Stop Hypertension trial. This model indexes micronutrient levels to energy levels to achieve a linear range of targeted intake in proportion to the energy intake. The Linear Index Model has several benefits: it takes advantage of indexing nutrients according to energy requirements, thus providing levels of nutrient intakes that can be readily achieved by foods; it is based on population consumption data, thus providing a realistic range of intakes for the experimental conditions; and it ensures distinct contrasts in experimental conditions. The Linear Index Model is a feasible and practical approach for establishing target levels of nutrients in feeding studies.

Blood Pressure↗
PubMed1999

Comparison of 4 nutrient databases with chemical composition data from the Dietary Approaches to Stop Hypertension trial. DASH Collaborative Research Group.

Accuracy of computerized nutrient databases is an important consideration in selecting a nutrient analysis system. We project compared the nutrient content of daily menus calculated from 4 microcomputer programs to chemical analysis of menus analyzed for the Dietary Approaches to Stop Hypertension (DASH) trial. Thirty-six menus were entered at 2 independent DASH sites using the ESHA Food Processor, Minnesota Nutrition Data System, Moore's Extended Nutrient Database, and Nutritionist IV databases. Food prepared according to these menus was chemically analyzed at the Food Analysis Laboratory Control Center at Virginia Polytechnic Institute and State University, Department of Biochemistry, Blacksburg. Estimates for 13 nutrients were compared: energy, total fat, saturated fat, monounsaturated fat, polyunsaturated fat, carbohydrate, protein, cholesterol, calcium, potassium, magnesium, iron, and sodium. The overall intraclass correlation between the 2 sites' data entry was 0.998; thus, values were averaged for analyses. Databases varied significantly in their mean deviations from chemical analyses values for saturated, monounsaturated, and polyunsaturated fatty acids, potassium, magnesium, and iron (P < .05); however, these differences were small (< 10%). Absolute deviations, which estimate the combined effect of bias and precision, were significantly different among databases for energy, saturated fatty acids, and polyunsaturated acids. Absolute differences from the laboratory values varied by < 15%, except for iron. All 4 databases were comparable in accuracy and precision and performed well. Criteria for database selection depends not only on overall database accuracy, especially for nutrients of interest, but also on the ease of use of the program, relevant features of the associated software; and cost.

Blood Pressure↗
PubMed1999

Dietary adherence in the Dietary Approaches to Stop Hypertension trial. DASH Collaborative Research Group.

Participants in controlled feeding studies must consume all study foods and abstain from all other foods. In outpatient studies in which adherence may be compromised by free-living conditions, promoting, documenting, and monitoring dietary adherence are necessary. In the Dietary Approaches to Stop Hypertension (DASH) trial, a thorough participant screening process, an orientation session, and a run-in feeding period before randomization aided in the selection of participants who would most likely adhere to the demands of the study protocol. Throughout the feeding period, various educational and motivational techniques were used to encourage DASH participants to adhere to the dietary protocol. Both objective and subjective methods documented excellent participant adherence. Daily monitoring of individual adherence was based on meal attendance, body weight measurements, and daily diaries. Urinary sodium, potassium, phosphorus, and urea nitrogen values and an anonymous poststudy survey were used to evaluate adherence at the end of the study. Most DASH participants adhered to the feeding regimen by consuming only study foods and no other foods. When adherence lapsed, participants generally cited the lack of menu variety as a reason. Successful participant adherence to the constraints of an outpatient controlled feeding study is possible with carefully selected participants and a variety of adherence-promoting strategies incorporated into the study protocol.

Blood Pressure↗
PubMed1998

Spinal motor patterns in the turtle.

Rhythmic alternation between ipsilateral hip flexors and extensors occurs during the normal pattern of fictive rostral scratching in response to unilateral midbody stimulation in D3-end turtles (complete spinal transection posterior to the forelimb enlargement). Unilateral midbody stimulation evokes rhythmic bursts of ipsilateral hip flexor activity with no hip extensor activity in D3-end turtles with D6-D7 contralateral hemisection (transverse hemisection anterior to the hindlimb enlargement). Bilateral midbody stimulation in these turtles evokes reconstruction of rhythmic alternation between intact side hip flexors and extensors. These normal motor patterns in response to two-site stimulation are reconstructed because one-site stimulation in this preparation activates only hip flexor rhythms (J. Neurosci. 18: 467). Hip flexor rhythms can therefore occur without hip extensor activation. This supports the concept that reciprocal inhibition between flexor and extensor interneurons is not required for flexor motor rhythm generation. Reciprocal inhibition, when present, also contributes to rhythmicity (J. Neurophysiol. 78: 3479; see also Currie and Gonsalves, this volume). Both mechanisms for rhythmicity are included in the Grillner unit burst generator model: hip flexor unit burst generators may be rhythmogenic in the absence of hip extensor activity and reciprocal inhibition contributes to rhythmogenesis. Contralateral midbody stimulation assisted in the activation of ipsilateral hip extensor rhythmicity during reconstructed rostral scratching. This result provides additional support for the hypothesis that a bilateral shared core of hip interneuronal circuitry plays a critical role in the generation of the normal pattern of fictive rostral scratching (J. Neurosci. 15: 4343).

Animals↗
PubMed1998

Reconstruction of flexor/extensor alternation during fictive rostral scratching by two-site stimulation in the spinal turtle with a transverse spinal hemisection.

Analyses of fictive scratching motor patterns in the spinal turtle with transverse hemisection provided support for the concept of bilateral shared spinal cord circuitry among neurons responsible for generating left- and right-side rostral, pocket, and caudal fictive scratching. Rhythmic bursts of hip flexor activity, the hip extensor deletion variation of fictive rostral scratching, were elicited by ipsilateral stimulation in the rostral scratch receptive field of a spinal turtle [transection at the segmental border between the second (D2) and third (D3) postcervical spinal segments] with a contralateral transverse hemisection one segment anterior to the hindlimb enlargement (at the D6-D7 segmental border). In addition, other sites were stimulated in this preparation: (1) contralateral sites in a rostral, pocket, or caudal scratch receptive field or (2) ipsilateral sites in a caudal scratch receptive field. A reconstructed fictive rostral scratch motor pattern of rhythmic alternation between hip flexor and hip extensor activation was produced by simultaneous stimulation of one site in the ipsilateral rostral scratch receptive field and another site in one of the other scratch receptive fields. This reconstructed rostral scratch motor pattern resembled the normal rostral scratch motor pattern produced by one-site rostral scratch stimulation of a spinal turtle (D2-D3 transection) with no additional transections. The observation of a reconstructed rostral scratch motor pattern produced by two-site stimulation in the spinal turtle with transverse hemisection supports the concept that hip extensor circuitry activated by stimulation of other scratch receptive fields is shared with circuitry activated by ipsilateral rostral scratch receptive field stimulation.

Animals↗
PubMed1998

The recovered memories debate: how reliable is the scholarship?

The disputed issues that comprise the recovered memories controversy are so important that they deserve the most careful and intellectually honest scholarship that the academic and professional community can muster. Drawing partly on illustrative material from the recent Health Care Analysis paper by Goodyear-Smith et al. and associated commentaries, it is argued that the controversy is not being well served. The rules of scholarship are too often broken, with the result that the products are often superficial, containing what should have been readily avoided factual errors, and are sometimes even misleading.

Adult↗
PubMed1998

Example of 2:1 interlimb coordination during fictive rostral scratching in a spinal turtle.

The usual interlimb coordination pattern during fictive rostral scratching in turtles is 1:1 coordination. We describe an example in a turtle of 2:1 coordination during fictive rostral scratching in which there were two cycles of ipsilateral hip flexor activity during each cycle of contralateral hip extensor activity. During 2:1 coordination, there were fluctuations in the ipsilateral hip flexor cycle period such that a larger ipsilateral hip flexor normalized period, which was associated with the onset of a contralateral hip extensor burst, alternated with a smaller ipsilateral hip flexor normalized period, which was associated with the absence of the onset of a contralateral hip extensor burst. These observations support the concept that contralateral circuitry modulates the timing of ipsilateral motor rhythms and therefore contributes to the production of the ipsilateral motor pattern for rostral scratching.

Animals↗
PubMed1991

The primary structures of four subunits of the human, high-molecular-weight proteinase, macropain (proteasome), are distinct but homologous.

Macropain (proteasome) is a high-molecular-weight proteinase complex composed of at least 13 electrophoretically distinct subunits. Previous work, including peptide mapping and limited amino acid sequencing, suggested that most of the subunits belong to an evolutionarily related group of different gene products (Lee et al. (1990) Biochim. Biophys. Acta. 1037, 178-185). In order to define the extent and pattern of subunit relatedness, and to determine the structural basis for possible similarities and differences in subunit functions, we are deducing the primary structures of macropain subunits by cDNA cloning and DNA sequence analysis. We report here the primary structures of four subunits. The data clearly demonstrate that the proteins represent different, but homologous gene products. Surprisingly, no evidence for homology with any other protein, including proteinases, was obtained. These results suggest that macropain is comprised of a previously unidentified family of evolutionarily related polypeptides. Because biochemical data indicate that macropain contains several different proteinase activities, the current results raise the possibility that the macropain complex is composed of a group of novel proteinases, distinct from those of other structurally identifiable proteinase families.

Amino Acid Sequence↗
PubMed1991

ATP-stimulated degradation of endogenous proteins in cell-free extracts of BHK 21/C13 fibroblasts. A key role for the proteinase, macropain, in the ubiquitin-dependent degradation of short-lived proteins.

Baby hamster kidney (BHK) 21/C13 cell proteins, labeled with [35S]methionine, [14C]leucine or [3H]leucine in intact cells, were degraded in soluble, cell-free extracts by an ATP-stimulated process. The stimulatory effect of ATP appeared to require ATP hydrolysis and was mediated to a large extent by ubiquitin. Although the cell extracts contained endogenous ubiquitin, supplementation with exogenous ubiquitin increased ATP-dependent proteolysis by up to 2-fold. Furthermore, antibodies against the E1 ubiquitin conjugating enzyme specifically inhibited both conjugation of [125I]ubiquitin to endogenous proteins and ATP/ubiquitin-dependent proteolysis. Addition of purified E1 to antibody-treated extracts restored conjugation and proteolysis. Proteins containing the amino acid analogues canavanine and azatryptophan were also degraded in vitro by an ATP/ubiquitin-dependent process but at a rate up to 2-fold faster than normal proteins. These results indicate that soluble, cell-free extracts of BHK cells can selectively degrade proteins whose rates of degradation are increased in intact cells. Treatment of cell-free extracts with antibodies against the high molecular weight proteinase, macropain, also greatly inhibited the ATP/ubiquitin-dependent degradation of endogenous proteins. Proteolysis was specifically restored when purified macropain L was added to the antibody-treated extracts. Treatment of cell extracts with both anti-macropain and anti-E1 antibodies reduced ATP/ubiquitin-dependent proteolysis to the same extent as treatment with either antibody alone. Furthermore, proteolysis could be restored to the double antibody treated extracts only after addition of both purified E1 and macropain. These results provide strong evidence for an important role for macropain in the ATP/ubiquitin-dependent degradation of endogenous proteins in BHK cell extracts.

Adenosine Triphosphate↗
PubMed1991

Feasibility of outpatient electrolyte balance studies.

Clinical studies requiring controlled electrolyte balance have traditionally been conducted in an inpatient (IP), metabolic ward setting. The purpose of this study was to test the feasibility of performing such studies in an outpatient (OP) clinical research setting. Focusing on sodium (Na) and potassium (K) balance, we retrospectively compared 28 subjects studied as OP vs 25 studied as IP on our metabolic ward. We assessed their adherence to our metabolic diets and their compliance with serial 24-hr urine collections. Dietary compliance was assessed by checksheet and urinary Na excretion; urine collection accuracy was determined by serial 24-hr creatinine excretion. The diets for both studies contained a low Na phase (10 mEq) and a high Na phase (200 mEq for IP and 250 mEq for OP), each lasting 1 week. When in balance on the low Na diet, 24-hr Na excretion was 4.6 +/- 0.7 mEq for OP and 13.4 +/- 2.2 mEq for IP, indicating excellent compliance with the low salt diet. Na excretion on the high Na diet was 184.5 +/- 7.4 mEq for OP and 195.3 +/- 9.6 mEq for IP. These values were not significantly different from each other; however, the OP were significantly less than their diet of 250 mEq Na (p less than 0.05). This difference may have been due to dermal Na losses. K excretion was also similar in the two groups. There was no significant difference in the reproducibility of individual multiple urinary creatinine measurements in OP vs IP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

The high molecular weight multicatalytic proteinase, macropain, exists in a latent form in human erythrocytes.

The high molecular weight multicatalytic proteinase, macropain, has been purified from human erythrocytes in two forms that differ in caseinolytic activity up to 100-fold. Each form has a native molecular weight of 600,000 and is composed of a number of subunits ranging in molecular weights from 35,000 to 21,000. Although the two proteinase forms share a number of electrophoretically indistinguishable subunits, there are also subunits unique to the respective forms. The less active proteinase represents a latent enzyme because it was fully activated by two procedures including dialysis against water and pretreatment with low concentrations of sodium dodecyl sulfate. These procedures caused differential changes in the caseinolytic and two peptidase activities of the proteinase. An Mr 35,000 subunit, characteristic of latent macropain, is immunologically related to at least one of the other components of active macropain and disappeared after proteinase activation by dialysis. Nevertheless, loss of this subunit was not the cause of the increased activity. These results suggest that the proteolytic activity of cells may be regulated by the activation of the latent form of macropain.

Caseins↗
PubMed1989

ATP-dependent mechanisms for protein degradation in mammalian cells.

The biochemical basis for ATP-dependent protein degradation observed in intact cells has been studied in cell-free extracts of baby hamster kidney fibroblasts. ATP plays at least two distinct roles in proteolysis. First, ATP is required for the covalent conjugation of ubiquitin to protein substrates. This modification markedly enhances the rates of degradation of some, but not all, proteins. Second, ATP appears to stimulate the activity of a protease capable of degrading both ubiquitinated and non-ubiquitinated proteins. This protease has several biochemical and catalytic features that resemble those of the previously described high molecular weight protease, macropain. Furthermore, antibodies against highly purified human erythrocyte macropain inhibit both ubiquitin-dependent and ubiquitin-independent pathways of ATP-dependent proteolysis. Such results provide evidence for an important role for macropain in ATP-dependent proteolysis in mammalian cells.

Adenosine Triphosphate↗