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Biomedical subjects

J W Anderson

Publications and source records attributed to J W Anderson.

At least 109 records · Page 6Linked to original sources

Dietary fibre, complex carbohydrate and coronary artery disease.

Animal studies indicate that viscous, soluble fibres such as psyllium, oat gum, guar gum and pectin have substantial hypocholesterolemic effects. Epidemiologic data suggest that the intake of complex carbohydrate and dietary fibre is associated in an inverse manner to risk for coronary artery disease (CAD). Two long term clinical trials indicate that increasing soluble fibre intake as part of a low fat, low cholesterol diet reduces serum cholesterol concentration from 3 to 5% below that for the low fat, low cholesterol diet. Short term, controlled clinical trials indicate that oat bran or beans, in a metabolic ward setting, decrease serum cholesterol concentrations of hypercholesterolemic individuals by 10 to 12%. Studies of free-living hypercholesterolemic individuals document that incorporation of oat products, psyllium or guar gum into the diet decreases serum cholesterol by 6 to 8%. Other studies suggest that increased fibre intake may decrease blood pressure slightly, assist in weight management, alter blood clotting factors, and increase insulin sensitivity. Intake of dietary fibre and complex carbohydrate appear to have a protective role for CAD. Further controlled clinical trials are required to examine the role of fibre and complex carbohydrate in prevention or regression of CAD.

Animals↗

Repair of spontaneously deamidated HPr phosphocarrier protein catalyzed by the L-isoaspartate-(D-aspartate) O-methyltransferase.

The non-enzymatic deamidation at residues Asn-12 and Asn-38 of Escherichia coli phosphocarrier protein, HPr, and the repair of the resulting L-isoaspartyl (or beta-aspartyl) derivatives, HPr-1 and HPr-2, by recombinant human S-adenosylmethionine-dependent L-isoaspartate-(D-aspartate) O-methyltransferase (EC 2.1.1.77) were investigated. HPr is a component of the bacterial phosphoenolpyruvate:sugar phosphotransferase system that is involved in the concomitant translocation and phosphorylation of many hexose sugars. The major products of the deamidation reaction, L-isoaspartyl (or beta-aspartyl) residues at positions 12 and 38, were found to be substrates for the L-isoaspartate-(D-aspartate) O-methyltransferase, an enzyme active on a wide variety of peptides and proteins containing these abnormal residues. This enzyme has been shown to catalyze the first step in a process that can convert L-isoaspartyl residues in peptides to normal L-aspartyl residues. The affinity of a recombinant human methyltransferase for HPr-1, a form deamidated at Asn-38, was relatively poor (Km = 3.6 mM), while a greater affinity was found for HPr-2, a form deamidated at both Asn-12 and Asn-38 (Km = 197 microM). When HPr-2 was incubated with S-adenosylmethionine and the methyltransferase, the bulk of the L-isoaspartyl residues at position 12 was converted to L-aspartyl residues. The major-by-product was the D-isoaspartyl form. The conversion of L-isoaspartyl residues at position 38 to L-aspartyl residues was less complete, reflecting the lower affinity of the methyltransferase for this site. The phosphohydrolysis activity of the repaired form was found to be midway between the form containing only L-aspartyl residues at positions 12 and 38 and the deamidated HPr-2 form.

Bacterial Proteins↗

A biochemical profile for predicting the chronic exposure of sheep to Microcystis aeruginosa, an hepatotoxic species of blue-green alga.

Sheep which grazed on the shoreline of a fresh-water lake which had a toxic bloom of Microcystis aeruginosa were studied for evidence of chronic poisoning, and a serum biochemical profile was developed to indicate sub-lethal, chronic poisoning in the sheep which had been exposed to microcystins. The profile included measurements of glutamate dehydrogenase (GLDH), gamma-glutamyl transferase (gamma GT), bile acids, bilirubin and albumin. Of 18 sheep which were exposed to M aeruginosa for more than three months, 100 per cent had high serum concentrations of bile acids, 94 per cent had high activities of GLDH and gamma GT, 83 per cent had high bilirubin and 72 per cent had low albumin concentrations compared with the median values of unexposed animals. Other sheep which were exposed for shorter periods, showed evidence of hepatic injury after one week of exposure. The majority of the sheep showed no preference for an alternative, uncontaminated source of water.

Animals↗

Responses of tracheobronchial receptors to halothane, enflurane, and isoflurane in anesthetized dogs.

We investigated the effects of halothane, enflurane, and isoflurane on the activity of 43 tracheobronchial slowly adapting stretch receptors (SARs) and 16 rapidly adapting irritant receptors (RARs) in 5 anesthetized, vagotomized, paralyzed, and artificially ventilated dogs. The 43 SARs were classified into 2 subtypes: (i) 17 low-threshold SARs with an expiratory discharge at FRC that were active throughout the respiratory cycle and (ii) 26 high-threshold SARs active only in inspiration. Ventilating the lungs with 5% of each anesthetic caused a significant increase in the inspiratory discharge of low-threshold SARs, whereas the expiratory discharge was inhibited or altogether silenced. While the activity of the majority of high-threshold SARs increased during the administration of the three volatile anesthetics, it decreased in those with a particularly high recruitment threshold. There was, however, a consistent increase in the pressure threshold at which all SARs were recruited. Ventilating the lungs with 5% of each anesthetic caused a significant decrease in activity of RARs. Our results indicate that all three halogenated anesthetics inhibit RARs at concentrations ranging from 1% to 5%.

Action Potentials↗

Relationship of weight loss to cardiovascular risk factors in morbidly obese individuals.

OBJECTIVES: This study critically examined the relationships between weight loss and changes in serum lipid and blood pressure levels. DESIGN: Eighty morbidly obese women and men were treated with an intensive very-low-calorie diet (VLCD) and behavioral education program. Body weight and blood pressure were measured weekly. Serum lipids were measured biweekly. RESULTS: Patients lost an average of 35.3 kg in 25.6 weeks. These values decreased significantly: fasting serum cholesterol, 15.1%; low density lipoprotein cholesterol, 17.0%; triglycerides, 14.2%; systolic blood pressure, 8.7%; and diastolic blood pressure, 10.2%. Changes in serum lipids and blood pressure were significantly (p < 0.001) correlated with baseline values and with changes in body mass index (BMI) after adjustment for baseline values. Patients maintained an average of 19.7 kg of their weight loss at the 2-year follow-up. CONCLUSIONS: Weight reduction through a multidisciplinary VLCD program significantly reduces risk factors for cardiovascular disease; for morbidly obese individuals, improvements in risk factors were significantly and linearly related to changes in the BMI.

Adult↗

Nutrition and health implications of dry beans: a review.

The nutrient composition of dry beans makes them ideally suited to meet two major dietary recommendations for good health--increased intake of starches and complex carbohydrates and decreased consumption of fat. Dry beans supply protein, complex carbohydrate, fiber and essential vitamins and minerals to the diet, yet are low in fat and sodium and contain no cholesterol. Both protective and therapeutic effects of bean intake have been documented. The antinutritional effects of dry beans, while minor, are of interest to nutrition professionals. Dry beans are an excellent way to increase dietary fiber consumption and most individuals can incorporate beans into their diet without difficulty if they do so gradually. Including dry beans in a health-promoting diet is especially important in meeting the major dietary recommendations to reduce risk for chronic diseases such as coronary heart disease, diabetes mellitus, obesity and cancer.

Diet, Fat-Restricted↗

Health benefits and practical aspects of high-fiber diets.

Over the past 20 y dietary fiber has emerged as a leading dietary factor in the prevention and treatment of chronic diseases. High fiber intakes are associated with lower serum cholesterol concentrations, lower risk of coronary heart disease, reduced blood pressure, enhanced weight control, better glycemic control, reduced risk of certain forms of cancer, and improved gastrointestinal function. Dietary fiber can be categorized into water-soluble and water-insoluble components. Dried beans, oat products, and certain fruits and vegetables are good sources of soluble fiber. Most plant foods are good sources of insoluble fiber and wheat bran is a concentrated form of insoluble fiber. Current guidelines advise a doubling of dietary fiber intake for Americans. Inclusion of ample servings of fruits and vegetables, whole grains, and dried beans and peas will help individuals meet these guidelines.

Dietary Fiber↗

Ten different dietary fibers have significantly different effects on serum and liver lipids of cholesterol-fed rats.

The comparative effects of 10 different dietary fibers on serum and liver lipids were investigated by feeding male Sprague-Dawley rats diets containing 10 g cholesterol + 2 g cholic acid/kg diet, with 60 g fiber/kg diet. Diets were fed for 3 wk; cellulose was the control fiber. Rats fed psyllium (rich in soluble fiber) had the lowest serum and liver cholesterol concentrations. Rats fed other soluble fiber-rich fibers (oat gum, guar gum and pectin) also had significantly lower serum and liver cholesterol concentrations than rats fed cellulose. Although feeding diets containing both soluble and insoluble fibers (soybean fiber and oat bran) did not significantly alter serum cholesterol, liver cholesterol values were significantly lower than those of cellulose-fed rats. Rats fed rice bran, predominantly an insoluble fiber source, had significantly higher liver cholesterol and significantly lower body weight gains and serum triglyceride concentrations than cellulose-fed rats. Values for serum and liver cholesterol were similar for rats were fed insoluble-rich fibers (corn bran, cellulose and wheat bran). These observations indicate that feeding dietary fibers rich in soluble fiber produces lower serum and liver cholesterol concentrations than does feeding commonly available sources of water-insoluble fiber.

Analysis of Variance↗

Aerosolized L-693,989 for Pneumocystis carinii prophylaxis in rats.

Water-soluble pneumocandin L-693,989, a potent antipneumocystis agent in the rat model for Pneumocystis carinii pneumonia (PCP), inhibits P. carinii cyst development and effectively prevents the development of PCP when used as a prophylactic agent (D. M. Schmatz, M. A. Powles, D. C. McFadden, L. Pittarelli, J. Balkovec, M. Hammond, R. Zambias, P. Liberator, and J. Anderson, Antimicrob. Agents Chemother. 36:1964-1970, 1992). However, because of limited oral bioavailability, this compound would likely be restricted to parenteral use in humans. As an alternative, the aerosol delivery of L-693,989 was explored to determine the dosing regimen required to prevent the onset of PCP. Rats with latent P. carinii infections were immunosuppressed continuously with dexamethasone to promote the onset of PCP. During the 6-week immunosuppression period, L-693,989 was delivered to rats as a nebulized solution (volume median diameter of 3.8 microns) via a nose exposure inhalation chamber. The efficiency of aerosol delivery to the lungs and the rate of clearance were determined by using radiolabelled compound. It was found that a daily dose of 0.7 micrograms of L-693,989 per lung or a weekly dose of 77.9 micrograms/lung effectively prevented the development of P. carinii cysts and trophozoites as well as the associated pneumonia commonly seen in rats with acute P. carinii infections. These results demonstrate that L-693,989 is potentially useful as an aerosol prophylactic agent for PCP.

Aerosols↗

Food-containing hypocaloric diets are as effective as liquid-supplement diets for obese individuals with NIDDM.

OBJECTIVE: This study was designed to determine if food-containing hypocaloric diets are as effective as liquid-supplement diets in promoting weight loss for obese individuals with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: Forty NIDDM subjects with body mass indexes (BMIs) of 30-40 kg/m2 were randomized to one of two 800-kcal diets for 12 weeks. Group A received liquid supplement only, and group B received supplement plus an evening meal. Both groups received an intensive behavioral education program. RESULTS: Weight loss and improvements in glycemic, blood lipid, and blood pressure parameters were similar for the two groups. Weight loss averaged 15.7 kg for the entire group. The need for insulin, anti-diabetes, and anti-hypertensive medication decreased significantly. No serious side effects were observed. CONCLUSIONS: Both food-containing and supplement diets providing 800 kcal a day effectively promote weight loss for obese individuals with NIDDM.

Body Mass Index↗

Effects of cholinergic, histaminergic, and peptidergic stimulation on pepsinogen secretion by isolated human peptic cells.

BACKGROUND: Whereas pepsin secretion by the human stomach has been extensively investigated, the characteristics of the peptide cell cannot be fully understood from in vivo studies. We therefore studied isolated human peptic cells to test directly cellular responses to different agents. METHODS: Eight endoscopic biopsy specimens yielded 10(6) cells, > 90% pure and > 95% viable. Secreted pepsinogen was measured with a sensitive hemoglobin digestion method at pH 2. RESULTS: Pepsinogen secretion was concentration-dependently stimulated by acetylcholine (ACh) (EC50 = 0.3 microM), cholecystokinin (CCK)-8 (2 nM), histamine (2 microM), and gastrin-I (30 nM) but not by bombesin or pentagastrin. ACh stimulation was inhibited 40 times more potently by atropine (IC50 = 12 nM) than by pirenzepine (IC50 = 0.5 microM). Histamine was inhibited by 10(-4) cimetidine. CCK-8 stimulation was inhibited 80% by the CCK-A-selective antagonist L364,718 (IC50 = 12 nM) but not by the CCK-B-selective antagonist L365,260. CONCLUSION: Isolated human peptic cells from endoscopic biopsy specimens secrete pepsinogen in response to ACh > CCK-8 > histamine > gastrin-I. The human peptic cell muscarinic-cholinergic receptor is not of the M1 subtype, and the CCK-8 response is predominantly mediated by a CCK-A receptor subtype.

Acetylcholine↗

Deamidation of HPr, a phosphocarrier protein of the phosphoenolpyruvate:sugar phosphotransferase system, involves asparagine 38 (HPr-1) and asparagine 12 (HPr-2) in isoaspartyl acid formation.

Histidine-containing protein, HPr, of the phosphoenolpyruvate:sugar phosphotransferase system in Escherichia coli, when incubated at elevated temperatures forms many species of protein. The two major species are HPr-1 and HPr-2, which have been shown to lack one or two amides, respectively (Anderson, B., Weigel, N., Kundig, W., and Roseman, S. (1971) J. Biol. Chem. 246, 7023-7033). The formation of HPr-1 and HPr-2 is shown to be pH-dependent and does not occur readily below pH 6. Investigation of the identities and properties of the two residues that deamidate involved creation of site-directed mutants at the 6 glutamine and 2 asparagine residues of HPr; description of their deamidation species by isoelectric focusing; determination of their relative antibody binding properties; assay of their phosphoacceptor and phosphodonor activities; characterization of tryptic and V8-protease peptides; obtaining two-dimensional nuclear magnetic resonance spectra of HPr, HPr-1, and several mutants. It was determined that the sequential deamidation of Asn-38 and Asn-12 yields HPr-1 and HPr-2. Both residues exist as Asn-Gly pairs, and both deamidations probably form isoaspartyl acid. HPr from Bacillus subtilis and Staphylococcus carnosus which also have Asn-Gly at residues 38 and 39 form HPr-1 species presumably by deamidation. HPr from Streptococcus faecalis which does not have Asn-38 does not form a HPr-1 species. The E. coli mutant HPrs, N12D and Q51E, residues that may be involved in the active site, had impaired phosphohydrolysis properties and decreased phosphoenolpyruvate:sugar phosphotransferase system activity.

Amino Acid Sequence↗

The involvement of the arginine 17 residue in the active site of the histidine-containing protein, HPr, of the phosphoenolpyruvate:sugar phosphotransferase system of Escherichia coli.

Histidine-containing protein, HPr, of the Escherichia coli phosphoenolpyruvate:sugar phosphotransferase system has an active site His-15 that is phosphorylated to form N delta 1-P-histidine. The nearby conserved residue, Arg-17, has been replaced by: lysine, histidine, glutamate, glycine, serine, and cysteine. All mutations resulted in impairment of the phosphoacceptor function of HPr with enzyme I: kcat/Km values between 6% (Ser-17) and 0.1% (Glu-17), relative to wild type. Several sugar-specific enzymes II had different responses. Both the Vmax and Km of enzyme IIN-acetylglucosamine were altered, while for enzyme IImannose only Km was affected, except for R17E. For both enzymes, kcat/Km values were between 0.5 and 3%, with R17E being 10-fold lower. Except for R17E, minimal effects were observed for enzyme IImannitol. These results suggest that there are different rate-limiting steps in the enzymes II. Phosphohydrolysis properties and the pKa values for His-15 and phosphorylated His-15 determined by NMR for both wild type and mutant HPrs suggest that Arg-17 is partly responsible for the instability of P-His-15 and the depressed pKa values in wild type HPr. Other feature(s) of the tertiary structure influence the protonation of His-15 and the phosphohydrolysis properties of phosphorylated His-15.

Amino Acid Sequence↗

Phosphoryl transfer between phosphorylated histidine-containing protein and histidine-containing protein is not autocatalytic.

Histidine-containing protein, HPr, is a phosphocarrier protein that is part of the bacterial phosphoenolpyruvate:sugar phosphotransferase system. HPr is phosphorylated by enzyme I, and P-HPr transfers the phosphoryl group to the IIA domain of a number of sugar-specific enzyme II complexes. Autocatalytic phosphoryl transfer between P-HPr and HPr has recently been reported [van Dijk, A. A., Eisermann, R., Hengstenberg, W., & Robillard, G. T. (1991) Biochemistry 30, 2876-2882]. Our results show that this phosphoryl transfer is due to an unidentified contaminant of HPr preparations. The phosphoryl transfer activity is not present in all HPr preparations. When present, the phosphoryl transfer activity can be removed by further purification or destroyed over time by resuspension of HPr preparations in water. There is no autocatalytic phosphoryl transfer between P-HPr and HPr.

Bacterial Proteins↗

Capsaicin-induced reflex bronchoconstriction in the newborn.

Although bronchoconstriction in response to C-fibre stimulation has been reported to be weak or absent in the newborn, pulmonary resistance and compliance have not been measured. We tested the hypothesis that capsaicin reflexly activates pulmonary efferent outflow to airway smooth muscle in the newborn. We measured breath-by-breath responses of inspiratory lung resistance (RLi) and dynamic compliance (CLdyn) in 13 newborn dogs and 4 newborn pigs during right heart injections of saline, capsaicin (25-50 micrograms/kg) and acetylcholine (ACh). Repeat capsaicin injections at 5 min intervals were made to test for desensitization in the newborn dog. All newborn dogs and 2 of 4 newborn pigs displayed a brisk bronchoconstriction; in the dog, RLi increased maximally by 97% +/- 13 (SE) and CLdyn decreased maximally by 32% +/- 2. In both species, initial capsaicin injections (CAP1) caused a long latency (time to peak heart rate 26.8 +/- 2 and 20 sec +/- 2.5) increase in heart rate (40% +/- 11 and 20.1% +/- 8.2 for the newborn dog and pig respectively). In the dog, but not the pig, capsaicin responses after the ACh trial (CAP2 and CAP3) caused a short latency bradycardia while the long latency tachycardia continued to be expressed in both species. The maximal changes in RLi and CLdyn, and the bradycardia, were reduced (i.e. desensitized) by 36%, 53% and 63% respectively if capsaicin injection was repeated within 5 min. Muscarinic blockade with atropine abolished the bronchoconstrictor and bradycardia responses to capsaicin but had no effect on the tachycardia. We conclude that the newborn possesses the neural circuitry to mount a bronchoconstrictor response to C-fibre stimulation. We speculate that the response is designed to reduce dead space and stabilize highly compliant airways of the newborn during the rapid shallow breathing that is typically associated with C-fibre stimulation.

Airway Resistance↗

Effects of halothane and isoflurane in the upper airway of dogs during development.

It has been previously found that volatile anesthetics significantly affect the activity of laryngeal receptors. In this study we have investigated the respiratory effects of these volatile anesthetics delivered into the upper airway of newborn and adult dogs. Experiments were performed on 17 5-14-day-old, 3 26-28-day-old and 3 adult dogs, anesthetized and breathing spontaneously through a tracheostomy. In the youngest age group, halothane decreased ventilation (VE) to 37.6 +/- 6.8% of control (mean +/- SE; P < 0.01) due to a decrease in both frequency and tidal volume. Peak inspiratory and expiratory flows, and esophageal pressure (Pes) were depressed also (60.8 +/- 6.5%, 51.6 +/- 7.1% and 66.5 +/- 8.1% of control, respectively; P < 0.01). Superior laryngeal nerve (SLN) section abolished the changes in VE, but residual significant decreases in peak flows and Pes were still present and disappeared only after topical anesthetization of the nasal cavities. Isoflurane had similar but weaker effects on VE (74.2 +/- 2.8% of control; P < 0.01), accompanied by a decrease in peak inspiratory and expiratory flows and Pes. SLN section abolished these changes. In the 26-28 day age group there was only a decrease in peak inspiratory airflow with the halothane challenge; isoflurane did not have any effect. In the adult dogs halothane caused only a marginal decrease in inspiratory time. The depressive effects of halothane and isoflurane should be considered when they are used for induction of anesthesia in newborns.

Age Factors↗

Effects of halothane, enflurane, and isoflurane on laryngeal receptors in dogs.

The effects of halothane, enflurane, and isoflurane on laryngeal receptors were investigated in 6 anesthetized dogs breathing spontaneously through a tracheostomy. Single unit action potentials were recorded from the peripheral cut end of the superior laryngeal nerve (SLN) while different concentrations of volatile anesthetics (1.25, 2.5, 5.0%) were administered in the expiratory direction at a constant air-flow (6 l/min) for 1 min through the functionally isolated upper airway. A total of 21 respiratory-modulated mechanoreceptors, 18 "irritant" receptors, and 7 cold receptors were studied. The overall results obtained from the 16 respiratory-modulated mechanoreceptors challenged with the 3 anesthetic gases disclosed a prevalent inhibitory effect and halothane proved to be the most effective of the 3 gases. The activity during both the inspiratory and expiratory phase was significantly reduced only by halothane (inspiratory phase, P < 0.01; expiratory phase, P < 0.05), while neither isoflurane nor enflurane caused significant changes in receptor activity. Of the 18 irritant receptors, 14 receptors increased their activity in a dose-related manner in response to one or more of the anesthetics although the effect of halothane was more pronounced than those of enflurane and isoflurane. All of the 7 cold receptors consistently increased their activity in a dose-related manner in response to halothane whereas 3 of 7 receptors were insensitive to enflurane and 4 of 7 receptors were insensitive to isoflurane. Our results indicate that, while all three commonly used anesthetics can have an effect on different types of laryngeal receptors, the effects of halothane are more pronounced than those of the other two gases in terms of changes in receptor activity.

Action Potentials↗

Diet, lipids and cardiovascular disease in women.

While hypercholesterolemia is an important risk factor for coronary heart disease in women, the responses of women and men to low-fat, low-cholesterol diets have not been carefully compared. This report summarizes three studies comparing responses of women and men. First, we evaluated the responses of women and men to public cholesterol screening and enrollment in a nutrition research study. Of the 3401 individuals who presented for initial screening, 56% were women and 44% were men. Of the eligible subjects, women (56%) were less likely than men (66%) to come to a second screening. After the second screening, however, study-eligible women (75%) were slightly more likely than men (67%) to enroll in the study. Next, serum and low-density lipoprotein cholesterol (LDL-C) values were compared for 64 women and 99 men in response to an American Heart Association (AHA) diet. Reductions in serum cholesterol (8.8 and 7.3%) and LDL-C (9.4 and 8.8%) were similar in women and men, respectively. Finally, serum lipid responses of 59 women and 87 men to a 12-month clinical trial with an AHA diet and a high-fiber AHA-type diet were compared. Both diets decreased serum cholesterol (10 and 13%) and LDL-C (14 and 18%), respectively, for the combined group of women and men. There were no significant differences between serum lipid responses for women and men. These observations suggest differences between the responses of women and men to screening and enrollment in a research study. However, responses of women and men to cholesterol-reducing diets appear similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗