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Biomedical subjects

L Sampson

Publications and source records attributed to L Sampson.

At least 19 recordsLinked to original sources

A prospective study of dietary glycemic load, carbohydrate intake, and risk of coronary heart disease in US women.

BACKGROUND: Little is known about the effects of the amount and type of carbohydrates on risk of coronary heart disease (CHD). OBJECTIVE: The objective of this study was to prospectively evaluate the relations of the amount and type of carbohydrates with risk of CHD. DESIGN: A cohort of 75521 women aged 38-63 y with no previous diagnosis of diabetes mellitus, myocardial infarction, angina, stroke, or other cardiovascular diseases in 1984 was followed for 10 y. Each participant's dietary glycemic load was calculated as a function of glycemic index, carbohydrate content, and frequency of intake of individual foods reported on a validated food-frequency questionnaire at baseline. All dietary variables were updated in 1986 and 1990. RESULTS: During 10 y of follow-up (729472 person-years), 761 cases of CHD (208 fatal and 553 nonfatal) were documented. Dietary glycemic load was directly associated with risk of CHD after adjustment for age, smoking status, total energy intake, and other coronary disease risk factors. The relative risks from the lowest to highest quintiles of glycemic load were 1.00, 1.01, 1. 25, 1.51, and 1.98 (95% CI: 1.41, 2.77 for the highest quintile; P for trend < 0.0001). Carbohydrate classified by glycemic index, as opposed to its traditional classification as either simple or complex, was a better predictor of CHD risk. The association between dietary glycemic load and CHD risk was most evident among women with body weights above average ¿ie, body mass index (in kg/m(2)) >/= 23. CONCLUSION: These epidemiologic data suggest that a high dietary glycemic load from refined carbohydrates increases the risk of CHD, independent of known coronary disease risk factors.

Adult↗

Structure-activity relationship study of steroidal and nonsteroidal inhibitors of the enzyme estrone sulfatase.

We report the initial results of a series of molecular modelling studies to investigate the structural properties of non-steroidal inhibitors required for inhibitory activity against the enzyme estrone sulfatase (ES) [the enzyme responsible for the conversion of nonactive (sulfated) estrone to the active (nonsulfated) estrone]. From the results of the present study, we conclude that the C(17) polar group may not be necessary for inhibitory activity and that the only requirement appears to be the mimicking of the steroid C(3) sulfonate group. To test our hypotheses, we have designed novel straight chain inhibitors based upon alkyl alcohols, which upon evaluation, have been shown to possess inhibitory activity (e.g., an inhibitor based upon trichloroethanol has been shown to possess 46% inhibition at 0.76mM).

Enzyme Inhibitors↗

Reproducibility and validity of dietary patterns assessed with a food-frequency questionnaire.

BACKGROUND: Recently, the analysis of dietary patterns has emerged as a possible approach to examining diet-disease relations. OBJECTIVE: We examined the reproducibility and validity of dietary patterns defined by factor analysis using dietary data collected with a food-frequency questionnaire (FFQ). DESIGN: We enrolled a subsample of men (n = 127) from the Health Professionals Follow-up Study in a diet-validation study in 1986. A 131-item FFQ was administered twice, 1 y apart, and two 1-wk diet records and blood samples were collected during this 1-y interval. RESULTS: Using factor analysis, we identified 2 major eating patterns, which were qualitatively similar across the 2 FFQs and the diet records. The first factor, the prudent dietary pattern, was characterized by a high intake of vegetables, fruit, legumes, whole grains, and fish and other seafood, whereas the second factor, the Western pattern, was characterized by a high intake of processed meat, red meat, butter, high-fat dairy products, eggs, and refined grains. The reliability correlations for the factor scores between the 2 FFQs were 0.70 for the prudent pattern and 0.67 for the Western pattern. The correlations (corrected for week-to-week variation in diet records) between the 2 FFQs and diet records ranged from 0.45 to 0.74 for the 2 patterns. In addition, the correlations between the factor scores and nutrient intakes and plasma concentrations of biomarkers were in the expected direction. CONCLUSIONS: These data indicate reasonable reproducibility and validity of the major dietary patterns defined by factor analysis with data from an FFQ.

Adult↗

A helical coat protein recognition domain of the bacteriophage P22 scaffolding protein.

The scaffolding protein of bacteriophage P22 directs the assembly of an icosahedral procapsid, a metastable shell that is the precursor for DNA packaging. The full-length protein has been shown previously to exist in a monomer-dimer-tetramer equilibrium of elongated and predominantly alpha-helical molecules. Two deletion-mutant fragments of the scaffolding protein, comprising amino acid residues 141 to 303 and 141 to 292, respectively, have been constructed, overexpressed in Escherichia coli, and purified. Removal of residues 1 to 140 yields a protein that is assembly-active both in vitro and in vivo, while the removal of the C-terminal 11 residues (293 to 303) leads to complete loss of scaffolding activity. Sedimentation analysis reveals that both scaffolding fragments exist in a monomer-dimer equilibrium governed by apparent dissociation constants Kd(141-303)=640 microM and Kd(141-292)=880 microM. Tetramer formation is not observed for either fragment; thus, the tetramerization domain of the scaffolding subunit resides in the N-terminal portion of the polypeptide chain. Examination of both fragments by circular dichroism, Raman and NMR spectroscopies indicates a highly alpha-helical fold in each case. Nonetheless, pronounced differences are observed between spectral signatures of the two fragments. Notably, Raman spectra of fragments 141-292 and 141-303 indicate that elimination of residues 293 to 303 results in unfolding of an alpha-helical coat protein "recognition" domain encompassing about 20 to 30 residues. The thermostability of fragment 141-303, monitored over a wide concentration range by circular dichroism and Raman spectroscopy, indicates a broad denaturation transition for the monomeric (low concentration) form, while more cooperative unfolding is observed for the dimeric (high concentration) form. A lesser increase in cooperativity upon dimerization is obtained for fragment 141-292. Additionally, the C-terminal recognition domain constitutes the most stable and cooperative unit in the 141-303 fragment. Measurement of hydrogen-isotope exchange kinetics in scaffolding fragments by time-resolved Raman spectroscopy shows that the C terminus is the only protected segment of the polypeptide chain. On the basis of the measured hydrodynamic and spectroscopic properties, a domain structure is proposed for the scaffolding subunit. The roles of these domains in P22 procapsid assembly are discussed.

Bacteriophage P22↗

Folate and vitamin B6 from diet and supplements in relation to risk of coronary heart disease among women.

CONTEXT: Hyperhomocysteinemia is caused by genetic and lifestyle influences, including low intakes of folate and vitamin B6. However, prospective data relating intake of these vitamins to risk of coronary heart disease (CHD) are not available. OBJECTIVE: To examine intakes of folate and vitamin B6 in relation to the incidence of nonfatal myocardial infarction (MI) and fatal CHD. DESIGN: Prospective cohort study. SETTING AND PATIENTS: In 1980, a total of 80082 women from the Nurses' Health Study with no previous history of cardiovascular disease, cancer, hypercholesterolemia, or diabetes completed a detailed food frequency questionnaire from which we derived usual intake of folate and vitamin B6. MAIN OUTCOME MEASURE: Nonfatal MI and fatal CHD confirmed by World Health Organization criteria. RESULTS: During 14 years of follow-up, we documented 658 incident cases of nonfatal MI and 281 cases of fatal CHD. After controlling for cardiovascular risk factors, including smoking and hypertension and intake of alcohol, fiber, vitamin E, and saturated, polyunsaturated, and trans fat, the relative risks (RRs) of CHD between extreme quintiles were 0.69 (95% confidence interval [CI], 0.55-0.87) for folate (median intake, 696 microg/d vs 158 microg/d) and 0.67 (95% CI, 0.53-0.85) for vitamin B6 (median intake, 4.6 mg/d vs 1.1 mg/d). Controlling for the same variables, the RR was 0.55 (95% CI, 0.41-0.74) among women in the highest quintile of both folate and vitamin B6 intake compared with the opposite extreme. Risk of CHD was reduced among women who regularly used multiple vitamins (RR=0.76; 95% CI, 0.65-0.90), the major source of folate and vitamin B6, and after excluding multiple vitamin users, among those with higher dietary intakes of folate and vitamin B6. In a subgroup analysis, compared with nondrinkers, the inverse association between a high-folate diet and CHD was strongest among women who consumed up to 1 alcoholic beverage per day (RR =0.69; 95% CI, 0.49-0.97) or more than 1 drink per day (RR=0.27; 95% CI, 0.13-0.58). CONCLUSION: These results suggest that intake of folate and vitamin B6 above the current recommended dietary allowance may be important in the primary prevention of CHD among women.

Adult↗

A prospective study of dietary fiber types and symptomatic diverticular disease in men.

To examine prospectively dietary fiber calculated from food composition values based on analytic techniques and specific dietary fiber types in relation to risk of diverticular disease, we analyzed data from a prospective cohort of 43,881 U.S. male health professionals 40-75 y of age at base line; subjects were free of diagnosed diverticular disease, colon or rectal polyps, ulcerative colitis and cancer. The insoluble component of fiber was inversely associated with risk of diverticular disease relative risk (RR) = 0. 63, 95% confidence interval (CI), 0.44-0.91, P for trend = 0.02, and this association was particularly strong for cellulose (RR = 0.52, 95% CI, 0.36-0.75, P for trend = 0.002). The association between diverticular disease and total dietary fiber intake calculated from the AOACstandards method was not appreciably different from results using the Southgate or Englyst method [for AOAC method, RR = 0.60, 95% CI, 0.41-0.87; for Southgate method, RR = 0.61, 95% CI, 0.42-0. 88; for Englyst method, RR = 0.60, 95% CI, 0.42-0.87, for the highest quintiles]. Our findings provide evidence for the hypothesis that a diet high in dietary fiber decreases the risk of diverticular disease, and this result was not sensitive to the use of different analytic techniques to define dietary fiber. Our findings suggest that the insoluble component of fiber was significantly associated with a decreased risk of diverticular disease, and this inverse association was particularly strong for cellulose.

Adult↗

Associations of plasma carotenoid concentrations and dietary intake of specific carotenoids in samples of two prospective cohort studies using a new carotenoid database.

Diet-plasma carotenoid associations were examined in samples of women and men from each cohort in the Nurses' Health Study and the Health Professionals Follow-Up Study. In each sample, participants completed two self-administered food frequency questionnaires with at least a 1-year interval and provided a blood specimen preceding the second food frequency questionnaire. Carotenoid intakes were estimated from values for the five major carotenoids found in human plasma, specifically, alpha- and beta-carotene, beta-cryptoxanthin, lutein, and lycopene, using the United States Department of Agriculture-National Cancer Institute Carotenoid Database, as well as updated values for tomato products. Pearson correlation coefficients were calculated to compare diet-plasma correlations over time by sex after adjustment for recognized covariates. Among nonsmoking women (n = 162), the adjusted diet-plasma carotenoid associations were 0.48 for alpha-carotene, 0.27 for beta-carotene and lutein, 0.32 for beta-cryptoxanthin, and 0.21 for lycopene. Among nonsmoking men (n = 110), diet-plasma correlations were 0.47 for alpha-carotene and lycopene, 0.35 for beta-carotene, 0.43 for beta-cryptoxanthin, and 0.40 for lutein. Correlations between total fruit or vegetable intake and each plasma carotenoid level were not as high as any of the calculated carotenoid intake using the new database values. The correlations observed in this study indicate that the new carotenoid database provides valuable information on specific carotenoid intake and may be useful in epidemiological studies that attempt to account for associations between fruit or vegetable intake and disease.

Aged↗

Cloning, purification, and preliminary characterization by circular dichroism and NMR of a carboxyl-terminal domain of the bacteriophage P22 scaffolding protein.

Assembly of double-stranded DNA viruses and bacteriophages involves the polymerization of several hundred molecules of coat protein, directed by an internal scaffolding protein. A 163-amino acid carboxyl-terminal fragment of the 303-amino acid bacteriophage P22 scaffolding protein was cloned, overexpressed, and purified. This fragment is active in procapsid assembly reactions in vitro. The circular dichroism spectrum of the fragment, as well as the 1D-NMR and 15N-1H HSQC spectra of the uniformly-labeled protein, indicate that stable secondary structure elements are present. Determination of the three dimensional packing of these elements into the folded scaffolding protein fragment is underway. Structure-based drug design targeted at structural proteins required for viral assembly may have potential as a therapeutic strategy.

Bacteriophage P22↗

Complications associated with central venous catheters used for the collection of peripheral blood progenitor cells to support high-dose chemotherapy and autologous stem cell rescue.

The purpose of this study was to review the incidence and type of complications associated with the insertion and use of central venous catheters for leukapheresis and high-dose chemotherapy with stem cell rescue. One hundred sixty-seven central venous catheters placed either at the transplant center or by various community surgeons were studied for insertion complications, inability to perform leukapheresis and incidence of infection. The overall incidence of hemo- or pneumothorax was 3.6%. Inability to pherese occurred in 13% of catheters placed by outside surgeons and 6.5% of catheters inserted at the transplant institution. Most often, these were due to malposition of the catheter too high in the superior vena cava or in other veins. Deep venous thrombosis was often related to this malposition and occurred in 4.8% of all patients. Pulmonary embolism was not seen in these patients despite the fact the catheters were often left in place during the thrombotic episode. Early or late-onset infections occurred in 6.5% of patients and were most often exit site infections. The incidence of complications of pheresis catheters is high but might be reduced by more attention to proper placement of the catheter closer to the right atrial/superior vena cava junction, and limiting insertion to a cadre of surgeons familiar with leukapheresis requirements.

Antineoplastic Combined Chemotherapy Protocols↗

Telomeres of the linear chromosomes of Lyme disease spirochaetes: nucleotide sequence and possible exchange with linear plasmid telomeres.

Bacteria of the spirochaete genus Borrelia have linear chromosomes about 950 kbp in size. We report here that these linear chromosomes have covalently closed hairpin structures at their termini that are similar but not identical to those reported for linear plasmids carried by these organisms. Nucleotide sequence analysis of the chromosomal telomeric regions indicates that unique, apparently functional genes lie within a few hundred bp of each of the telomeres, and that there is an imperfect 26 bp inverted repeat at the two telomeres. In addition, we characterize a major chromosomal length polymorphism within the right telomeric regions of various Borrelia isolates, and show that sequences similar to those near the right telomere are often found on linear plasmids in B. burgdorferi (sensu stricto) isolates from nature. Sequences similar to a number of other regions of the chromosome, including those near the left telomere, were not found on B. burgdorferi plasmids. These observations suggest that there has been historical exchange of genetic information between the linear plasmids and the right end of the linear chromosome.

Amino Acid Sequence↗

Pancreatic carcinoma cell killing via adenoviral mediated delivery of the herpes simplex virus thymidine kinase gene.

OBJECTIVE: Use of adenoviral mediated delivery of the herpes simplex virus thymidine kinase (HSV-TK) gene as a gene therapy strategy for carcinoma of the pancreas. SUMMARY BACKGROUND DATA: Expression of HSV-TK selectively sensitizes cells to the nucleoside analog ganciclovir (GCV). This strategy has been used to treat other compartmentalized tumor models. Therefore, the containment of pancreatic carcinoma makes it amenable to this gene therapy approach. METHODS: A recombinant adenoviral vector encoding the HSV-TK gene was used to induce GCV sensitivity and test the potential bystander effect in established pancreatic carcinoma cell lines and patient-derived tumor material. Additionally, Balb/C nude mice were injected intraperitoneally with human pancreatic carcinoma cells and treated with GCV (50 mg/kg per day) for 14 days. RESULTS: Expression of the HSV-TK gene elicited a significant bystander effect in the presence of GCV. Pancreatic tumor cells injected intraperitoneally into nude mice resulted in significant tumor formation. Treatment of animals with AdCMVHSV/HSV-TK and GCV induced a dramatic decrease in overall tumor burden for up to 8 weeks post-GCV treatment. CONCLUSIONS: Pancreatic carcinoma cells are highly susceptible to transduction with recombinant adenoviral vector and elicit a potent bystander effect on neighboring tumor cells. Additionally, in vivo treatment of tumor-bearing animals results in dramatic reduction of overall tumor burden, thus providing the rationale for molecular chemotherapy of pancreatic carcinoma.

Adenoviridae↗

Molecular genetic analysis of bacteriophage P22 gene 3 product, a protein involved in the initiation of headful DNA packaging.

Bacteriophage P22 DNA packaging events occur in processive series on concatemeric phage DNA molecules. At the point where such series initiate, the DNA is recognized at a site called pac, and most molecular left ends are generated within six short regions called end sites, which are present in a 120 base-pair region surrounding the pac site. The bacteriophage P22 genes 2 and 3 proteins are required for successful generation of these ends and DNA packaging during progeny virion assembly. Mutants lacking the 162-amino-acid gene 3 protein replicate DNA and assemble functional procapsids. In this report we describe the nucleotide changes and DNA packaging phenotypes of a number of missense mutations of gene 3, which give the phage a higher than normal frequency of generalized transduction. In cells infected by these mutants, more packaging events initiate on the host chromosome than in wild-type infections, so the mutations are thought to affect the specificity of packaging initiation. In addition to having this phenotype, these mutations affect the process of phage DNA packaging in detectable ways. They may: (1) alter the target site specificity for packaging; (2) make target site recognition more promiscuous; (3) affect end site utilization; (4) alter the pac site; and (5) cause apparent random DNA packaging series initiation on phage DNA.

Bacteriophage P22↗

Bacteriophage P22 portal protein is part of the gauge that regulates packing density of intravirion DNA.

The complex double-stranded DNA bacteriophages assemble DNA-free protein shells (procapsids) that subsequently package DNA. In the case of several double-stranded DNA bacteriophages, including P22, packaging is associated with cutting of DNA from the concatemeric molecule that results from replication. The mature intravirion P22 DNA has both non-unique (circularly permuted) ends and a length that is determined by the procapsid. In all known cases, procapsids consist of an outer coat protein, an interior scaffolding protein that assists in the assembly of the coat protein shell, and a ring of 12 identical portal protein subunits through which the DNA is presumed to enter the procapsid. To investigate the role of the portal protein in cutting permuted DNA from concatemers, we have characterized P22 portal protein mutants. The effects of several single amino acid changes in the P22 portal protein on the length of the DNA packaged, the density to which DNA is condensed within the virion, and the outer radius of the capsid have been determined. The results obtained with one mutant (NT5/1a) indicate no change (+/- 0.5%) in the radius of the capsid, but mature DNA that is 4.7% longer and a packing density that is commensurately higher than those of wild-type P22. Thus, the portal protein is part of the gauge that regulates the length and packaging density of DNA in bacteriophage P22. We argue that these findings make models for DNA packaging less likely in which the packing density is a property solely of the coat protein shell or of the DNA itself.

Base Sequence↗

The assessment of alcohol consumption by a simple self-administered questionnaire.

The authors evaluated the reproducibility and validity of alcohol consumption measured by a mailed, self-administered questionnaire in two large prospective studies. Subsamples of 173 women and 136 men from these cohorts completed two food-frequency questionnaires and multiple 1-week diet records (four for women and two for men) and provided a fasting blood sample. Intakes of alcohol reported over the previous year by food frequency questionnaire 2 correlated highly with intake assessed by multiple week diet records completed over this period (Spearman r = 0.90 in women and 0.86 in men). Mean daily alcohol intake as assessed by the diet records and the questionnaires was very similar. Serum high density lipoprotein cholesterol levels were significantly correlated with alcohol intakes estimated from the questionnaire (r = 0.40 in women and 0.35 in men) and for the diet records (r = 0.33 in women and 0.38 in men). Four years after completing the diet records, women were asked to report their alcohol intake of 4 years earlier; this estimate was highly correlated with the diet records (r = 0.84) and with the earlier high density lipoprotein cholesterol (r = 0.40). These data suggest that a simple self-administered questionnaire can provide useful estimates of alcohol intake over an extended period of time in subjects participating in prospective epidemiologic studies.

Adult↗

Fine structure genetic and physical map of the gene 3 to 10 region of the bacteriophage P22 chromosome.

The mechanism by which dsDNA is packaged by viruses is not yet understood in any system. Bacteriophage P22 has been a productive system in which to study the molecular genetics of virus particle assembly and DNA packaging. Only five phage encoded proteins, the products of genes 3, 2, 1, 8 and 5, are required for packaging the virus chromosome inside the coat protein shell. We report here the construction of a detailed genetic and physical map of these genes, the neighboring gene 4 and a portion of gene 10, in which 289 conditional lethal amber, opal, temperature sensitive and cold sensitive mutations are mapped into 44 small (several hundred base pair) intervals of known sequence. Knowledge of missense mutant phenotypes and information on the location of these mutations allows us to begin the assignment of partial protein functions to portions of these genes. The map and mapping strains will be of use in the further genetic dissection of the P22 DNA packaging and prohead assembly processes.

Chromosome Mapping↗

Contributions of specific foods to absolute intake and between-person variation of nutrient consumption.

Contributions of specific foods and supplements to absolute intake and between-person variance in consumption of 19 macronutrients, vitamins, and minerals were examined using dietary records of all foods consumed over 4 weeks by 194 US nurses aged 34 to 59 years. To measure their contribution to absolute nutrient intake, we ranked foods by the percentage of the population's total nutrient intake that they provided. To assess the degree to which differences in consumption of specific foods explain between-person variability in nutrient intake, we re-ranked the 20 foods contributing most to absolute intake of each nutrient as independent variables in stepwise multiple regression analyses predicting total intake of that nutrient. The increase in percentage of the variance in nutrient intake explained by the addition of a food to the progressively larger list of food items (expressed as the cumulative R2) served as the measure of contribution to variation in intake. Some nutrients had only a few major sources and were assessed relatively well by a small number of foods. For preformed vitamin A without supplements, 10 foods accounted for 82% of the absolute intake and 98% of total variance. The corresponding percentages for absolute intake and total variance, respectively, were 66% and 94% for beta-carotene; 77% and 92% for cholesterol; and 71% and 95% for vitamin C without supplements. In contrast, 20 foods accounted for only 54% of the absolute intake and 73% of the variance for total energy intake; 58% and 89%, respectively, for total carbohydrates; and 59% and 84%, respectively, for potassium.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Food-based validation of a dietary questionnaire: the effects of week-to-week variation in food consumption.

The reproducibility and validity of responses for 55 specific foods and beverages on a self-administered food frequency questionnaire were evaluated. One hundred and seventy three women from the Nurses' Health Study completed the questionnaire twice approximately 12 months apart and also recorded their food consumption for seven consecutive days, four times during the one-year interval. For the 55 foods, the mean of correlation coefficients between frequencies of intake for first versus second questionnaire was 0.57 (range = 0.24 for fruit punch to 0.93 for beer). The mean of correlation coefficients between the dietary records and first questionnaire was 0.44 (range = 0.09 for yellow squash to 0.83 for beer and tea) and between the dietary records and the second questionnaire was 0.52 (range = 0.08 for spinach to 0.90 for tea). Ratios of within- to between-person variance for the 55 foods were computed using the mean four one-week dietary records for each person as replicate measurements. For most foods this ratio was greater than 1.0 (geometric mean of ratios = 1.88), ranging from 0.25 (skimmed milk) to 14.76 (spinach). Correlation coefficients comparing questionnaire and dietary record for the 55 foods were corrected for the within-person variation (mean corrected value = 0.55 for dietary record versus first questionnaire and 0.66 versus the second). Mean daily amounts of each food calculated by the questionnaire and by the dietary record were also compared; the observed differences suggested that responses to the questionnaire tended to over-represent socially desirable foods. This analysis documents the validity and reproducibility of the questionnaire for measuring specific foods and beverages, as well as the large within-person variation for food intake measured by dietary records. Differences in the degree of validity for specific foods revealed in this type of analysis can be useful in improving questionnaire design and in interpreting findings from epidemiological studies that use the instrument.

Adult↗