Maillard reactions involving proteins and carbohydrates in vivo: relevance to diabetes mellitus and aging.
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Aging↗
Biomedical subjects
V J Stevens
Publications and source records attributed to V J Stevens.
Modification of hemoglobin by ninhydrin.
The Strecker degradation reaction was evaluated as a means of modifying hemoglobin in vitro, utilizing ninhydrin as a model compound. Ninhydrin led to modification of hemoglobin (when incubated with hemoglobin or red cells) at physiologic temperature and pH. Isoelectric focusing documented the formation of new hemoglobin bands, all with decreased (more negative) isoelectric points that hemoglobin A. Both alpha and beta chains were modified to an equal degree, although electrophoretic studies documented two modified species of alpha-chains and three modified species of beta-chains. Amino acid analysis of modified hemolysate following NaB3H4 reduction revealed peaks that coeluted with deaminated valine, epsilon-deaminated lysine, and a product with the guanidino group of arginine. The oxygen affinity of hemoglobin increased following its incubation with increasing concentrations of ninhydrin. These studies suggest that ninhydrin is representative of a class of carbonyl compounds that could be utilized to specifically modify that structure and function of hemoglobin variants.
Chemical Phenomena↗
Nonenzymatic glycosylation, sulfhydryl oxidation, and aggregation of lens proteins in experimental sugar cataracts.
The formation of sugar-cataracts has been hypothesized to involve the nonenzymatic glycosylation, sulfhydryl oxidation, and aggregation of lens proteins. Cataractous lenses of diabetic and galactosemic rats were analyzed for glycosylated lysine residues in crystallins. A five- and a ten-fold increase in glycosylated lysine residues was measured in galactose and diabetic cataracts, respectively. The modification was predominant in the insoluble fraction of the lens homogenate. The proteins were further examined for the presence of disulfide bonds and high molecular weight aggregates. After careful disruption of the lens in a nitrogen environment, a cloudy solution was obtained from cataractous lenses whereas a clear solution was obtained from normal lenses. The absorbance at 550 nm of the solution of both the galactosemic and the diabetic cataracts could be decreased by approximately 50% with the addition of dithioerythritol (50 mM). The presence of high molecular weight aggregates was ascertained by sucrose gradient centrifugation and gel filtration chromatography. The proteins were heterogenous in size and showed a mol wt range of 36 to greater than 176 million daltons. Treatment with dithioerythritol induced a marked decrease in the amount of high molecular weight proteins. These data suggest that sugar cataracts of experimental animals have, in common with human cataracts, the presence of high molecular weight aggregates which are in part linked by disulfide bonds.
Alloxan↗
Role of nonenzymatic glycosylation in the development of the sequelae of diabetes mellitus.
The increased level of the glycosylated hemoglobin (hemoglobin A1c) in the diabetic patient has proved to be an interesting clue to understanding the biochemical basis of the sequelae of diabetes. This minor hemoglobin, which arises as nonenzymatic postsynthetic addition of glucose to hemoglobin A, acts as an indicator molecule for the glucose environment over a 3-5-wk period prior to measurement. Reasoning that a similar glycosylation reaction could be occurring with other body proteins, we have studied the ocular lens. The lens, like the erythrocyte, is not dependent on insulin for glucose concentration in the extracellular milieu that would be elevated in the diabetic state. These studies have revealed that a high glucose in vivo or an increased glucose or glucose-6-phosphate concentration in vitro leads to the glycosylation of epsilon-amino groups of lysine residues in bovine and rat lens crystallins. This glycosylation imparts an increased susceptibility of the crystallins to sulfhydryl oxidation. Disulfide crosslinks result in the formation of high molecular weight aggregates and an opalescence of the crystallin solutions.
Animals↗
Diabetic cataract formation: potential role of glycosylation of lens crystallins.
A high glucose concentration in vivo or an increased glucose of glucose 6-phosphate concentration in vitro has been found to lead to the glycosylation of epsilon-amino groups of lysine residues in bovine and rat lens crystallins. In vitro, this glycosylation imparts an increased susceptibility of the crystallins to sulfhydryl oxidation. Disulfide crosslinks result in the formation of high molecular weight aggregates and an opalescence in the crystallin solutions. The addition of reducing agents prevents as well as reverses the formation of high molecular weight aggregates and the opalescence of the crystallins. These phenomena suggest a new interpretation of previous results on cataract formation and a new approach for development of drugs to prevent cataracts.
Animals↗
The formation of hb aic as a biochemical model for the sequelae of diabetes.
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Diabetes Mellitus↗
Nonenzymatic glycosylation of hemoglobin.
The incubation of dialyzed hemoglobin A with a number of phosphorylated glycolytic intermediates leads to the formation of covalent hemoglobin adducts that co-chromatograph with hemoglobin AIb. Phosphorylated hexoses (glucose-6-P, fructose-6-P, fructose-1,6-P2) and trioses (glyceraldelyde-3-P, dihydroxyacetone-P) containing a free aldehyde or ketone can glycosylate hemoglobin A nonenzymatically. From 7 to 12% of the hemoglobin can be modified after a 72-h incubation of an equimolar mixture of hemoglobin A and the phosphorylated intermediate. No significant formation of adduct was seen with a sugar alone (glucose, fructose) or glycolytic intermediate which had a blocked aldehyde (glucose-1-P, glucose-1,6-P2, UDP-glucose). The addition of an equimolar amount of 2,3-diphosphoglycerate reduced adduct formation. Evidently, the phosphate is needed to orient and stabilize the intermediate in the bisphosphoglycerate pocket of hemoglobin so that the addition reaction can proceed. All of the hemoglobin A adducts were indistinguishable form hemoglobin AIb by ion exchange chromatography and isoelectric focusing. The hemoglobin A-glucose-6-P adduct and hemoglobin AIb had a NaB3H4-reducible linkage in the beta chain. The concentration of hemoglobin AIb is elevated in patients with diabetes mellitus. This presumably reflects the increased concentrations of glycolytic intermediates (glucose-6-P, fructose-6-P, fructose-1,6-P2, dihydroxyacetone-P) which were found to be significantly elevated in the red cells of diabetic patients as compared with normal controls.
Adult↗
Biochemical validation of smoking status: pros, cons, and data from four low-intensity intervention trials.
Biochemical validation of smoking status has long been considered essential, but recent reports have questioned its utility in certain kinds of field trials. We describe efforts to biochemically validate self-reports of smoking cessation from participants in four large-scale randomized trials in outpatient clinics, hospitals, worksites, and dental clinics. These studies included over 5,000 adults smokers who participated in the population-based low-intensity intervention evaluations. At a 1-year follow-up, 798 subjects reported no tobacco use. We attempted to verify these reports using saliva continine/carbon monoxide validation procedures. Overall, there was a moderately high nonparticipation rate (27%), a low disconfirmation rate (4%), and a high self-reported relapse rate (12%) in the interval between survey and biochemical validation. There were no differences between intervention and control conditions on any of the above variables. Longer durations of self-reported abstinence were strongly related to increased probability of biochemical confirmation. Differences in results across projects were related to how biochemical validation was conducted. These results, as well as statistical power considerations, raise questions about whether biochemical validation procedures are practical, informative, or cost-effective in such population-based, low-intensity intervention research.
Adult↗
Tobacco cessation interventions in health care settings: rationale, model, outcomes.
Health care settings provide opportunities to reach populations of tobacco users with personalized cessation assistance. We describe a model for doing so which emphasizes a team approach, minimizes the burden on clinicians, and uses brief counseling by allied professionals, videos, written materials, and telephone calls to augment clinician advice. The model has been implemented in several diverse settings including outpatient, inpatient, and dental clinic managed care; fee-for-service dentistry and pediatric practices; and planned parenthood clinics. Data from several randomized trials support the effectiveness of the approach. The brief, low-intensity interventions derived from the model appear to be sustainable on a routine basis in many settings.
Administration, Cutaneous↗
Implementation of "Open Airways" as an educational intervention for children with asthma in an HMO.
This article describes the adaptation and implementation of an existing pediatric asthma-management educational program, Open Airways, for members of a large group practice health maintenance organization. Seventy-four children ages 4 to 14 years and their families were randomized into one of seven class cohorts as part of a larger study of pediatric asthma management. The Open Airways program was modified to increase the emphasis on behavioral change and medication information and to reflect the different sociodemographic makeup of the population, compared with that for which the program was developed. Of the 74 families, 62 attended at least one class, and 47 of these attended five or more classes. Evaluations after classes suggest an increase in parental confidence in managing their child's asthma and an earlier use of medications. Health care providers may be able to adapt similar programs for successful use with their populations.
Adolescent↗
Patterns of nicotine gum use in a health maintenance organization.
Nicotine chewing gum is designed as an aid to smokers who intend to stop smoking. However, the efficacy of the gum in general medical practice has been questioned. This study describes the extent of nicotine chewing gum use among health maintenance organization members, the characteristics of prescribers and users, and the patterns of gum use over a two-year period. About 0.4 percent of Kaiser Permanente, Northwest Region members were exposed to the gum. Over the two-year observation period, 1970 members received at least one box (96 pieces) of the gum. Almost 70 percent of users received only one box of the gum. About 1.5 percent of users appeared to use the gum continuously at a daily dosage around the level needed to replace the nicotine addiction among most smokers, and for longer than the recommended three months. Another 2.5 percent appeared to use the gum continuously but at less than a nicotine-addiction replacement dose for longer than the recommended maximum of six months. The presence of a prepaid prescription drug benefit directly affected whether or not a person received the gum and how long he used it. The extreme variation in the patterns of use raises the questions of why the gum is used in this manner, and how effective it is when used in this manner.
Adult↗
Changes in smoking associated with hospitalization: quit rates, predictive variables, and intervention implications.
BACKGROUND: Hospitalization can provide one of the most opportune times to prompt smoking cessation. This study determined the frequency of various smoking cessation related behaviors occurring during and following hospitalization and identified variables associated with these outcomes. METHODS: A sample of 526 HMO members who smoked prior to hospitalization and were hospitalized for nonpregnancy related, nonterminal conditions were surveyed to assess the natural history of smoking cessation associated with hospitalization. RESULTS: Three events were studied: not smoking while hospitalized (51% of subjects), attempting to quit following hospitalization (37%), and smoking status one year after hospitalization (16% abstinent). Similar factors were associated with not smoking in the hospital and quit attempts: older persons and patients with circulatory/respiratory diagnoses were only half as likely to smoke in the hospital as other patients and twice as likely to try to quit. Different variables predicted smoking status at follow-up: heavier smokers were significantly more likely to stop (26% cessation) than light or moderate smokers (10% and 11% cessation, respectively). DISCUSSION: The hospital may be an effective setting for smoking cessation programs, especially those aimed at heavy smokers. Research is needed to determine whether smokefree hospital policies alter smoking rates following hospitalization.
Adolescent↗
The HMO as a health promotion laboratory.
HMOs offer unparalleled opportunities as a setting for health promotion research while providing the health care system with direct and immediate benefits. The special advantages of doing health promotion research in an HMO include easy access to a large, relatively stable population; access to all aspects of the health care system; access to a unified, comprehensive medical record; and working within an organization that views health promotion activities as an essential part of its mission. This article reviews these advantages and illustrates how they have been used in a diverse series of research and demonstration projects conducted within the Northwest Region of Kaiser Permanente.
Data Collection↗
Smoking behavior and attitudes of employees of a large HMO before and after a work site ban on cigarette smoking.
Smoking-related data collected during 1976-87 by anonymous cross-sectional surveys of nonphysician employees of a large medical care organization were used to assess how a work site smoking ban affected employees' smoking behavior and attitudes. The smoking ban was implemented at 11 work sites at various times during 1985-86. All work sites had three or more pre-ban surveys and one or two post-ban surveys. The majority of employees reported support for the smoking ban. The ban's effects were assessed by comparing observed post-ban rates with expected rates projected from secular trends in the pre-ban data by the use of logistic regression models that included age, sex, education, and job class as covariates. The work site smoking ban had a substantial effect on the presence of smoke in the work environment, but no short-term effect on smoking prevalence or attempts to quit. The apparent effect of the ban on quantity of cigarettes smoked was assessed by a pre-ban and post-ban analysis of the 1986-87 survey data. A nonequivalent post-ban and post-ban comparison was used to estimate the secular trend. A significant reduction of 1.4 cigarettes per day (P = 0.022) was found in smokers' rate during working hours.
Adult↗
Hemoglobin glycosylation as a model for modification of other proteins.
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Aged↗