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J M Neuhaus

Publications and source records attributed to J M Neuhaus.

At least 37 records · Page 2Linked to original sources

Living arrangements, changes in living arrangements, and survival among community dwelling older adults.

OBJECTIVES: This study examines whether living arrangements and changes in living arrangements are associated with survival among older community-dwelling adults, and whether differences in health status account for observed differences in survival. METHODS: The sample consisted of 5085 persons aged 70 years or older who had participated in the Longitudinal Study of Aging in 1984 and 1986. Proportional hazards models were used to examine associations of survival time through 1990 with living arrangements in 1984 and with changes in living arrangements from 1984 to 1986. RESULTS: Women who lived with someone other than a spouse at baseline or who changed from living with a spouse to living with someone other than a spouse were at greater risk of dying than women in other living arrangements, independent of health status or functioning. Among men, survival time was not generally associated with baseline living arrangements. CONCLUSIONS: Older adults who live alone or who change from living with someone to living alone do not have an increased mortality risk. However, living with or changing to living with someone other than a spouse may be associated with increased mortality risk.

Activities of Daily Living↗

Variation among rheumatologists in clinical outcomes and frequency of office visits for rheumatoid arthritis.

OBJECTIVE: To estimate the variation among rheumatologists in clinical outcomes and frequency of office visits for patients with rheumatoid arthritis (RA), after accounting for patient demographic and clinical characteristics and treatments prescribed. METHODS: Multiple regression analysis using random effects for rheumatologists and adjustments for patient characteristics and treatments received, based on data derived from a panel study of persons with RA. RESULTS: During the years 1984-1993, rheumatologists accounted for a moderate amount of the total variation in clinical outcomes and nearly one-third of the total variation in frequency of office visits. For example, in 1993 rheumatologist associated variation in 4 clinical outcomes ranged from 16 to 25%, while the variation in office visit frequency attributable to rheumatologists stood at 46% of the total variation. However, rheumatologist associated variation in clinical outcomes was not statistically significant in any year, while variation in office visits was highly significant in all years (p < or = 0.0001). Although there was an increase in the percentage of variation attributable to rheumatologists for all outcomes examined across the years of this study, the time trend reached statistical significance only for frequency of office visits (2.4% per year; p = 0.0135) and functional status (1.6% per year; p = 0.0034). CONCLUSION: The magnitude and strength of rheumatologist associated variation in frequency of office visits, without comparable strength in the variation in clinical outcomes, may suggest inefficiencies in the use of resources for the care of persons with RA. Further work is needed to directly examine the relationship between health outcomes and resource utilization.

Adult↗

Human immunodeficiency virus-related oral manifestations and gender. A longitudinal analysis. The University of California, San Francisco Oral AIDS Center Epidemiology Collaborative Group.

BACKGROUND: Because human immunodeficiency virus (HIV) infection affects an increasing number of women in the United States, we investigated the role played by gender in the occurrence of HIV-related oral conditions. METHODS: As part of a 4-year prospective study of 3 epidemiological cohorts, oral and physical examinations (including blood tests) were performed on HIV-infected men (n = 200) and women (n = 218) at 6-month intervals. Our outcome variables included oral conditions commonly associated with HIV infection: hairy leukoplakia, candidiasis, ulcers, warts, non-Hodgkin lymphoma, Kaposi sarcoma, and parotid enlargement. RESULTS: Only hairy leukoplakia, candidiasis, and ulcers were observed. The occurrence of hairy leukoplakia and candidiasis was higher in men (22% and 24%, respectively) than in women (9% and 13%, respectively) during the study period. A regression model for longitudinal data (generalized estimating equation) disclosed that the odds of having hairy leukoplakia were 2.5 times higher for men than for women, after controlling for CD4+ cell count, race, and injecting drug use (95% confidence interval, 1.34-4.76; P = .003). Length of follow-up did not confound this association. A weaker association was found between the occurrence of oral candidiasis and gender (adjusted odds ratio, 1.85; 95% confidence interval, 1.0-3.43; P = .05). CONCLUSIONS: In this sample of HIV-infected adults, we found that men were significantly more likely to have hairy leukoplakia than were women. The hairy leukoplakia-gender association merits further investigation, because it may be related to a gender difference in the mode of expression of Epstein-Barr virus.

Adult↗

Plant chitinases use two different hydrolytic mechanisms.

Bacterial, fungal, animal, and some plant chitinases form family 18 of glycosyl hydrolases. Most plant chitinases form the family 19. While some chitinases also have lysozyme activity, animal lysozymes belong to different families. For glycosyl hydrolases, two reaction mechanisms are possible, leading to either retention or inversion of the anomeric configuration. We analyzed by HPLC the stereochemical outcome of the hydrolysis catalyzed by cucumber and bean chitinases, belonging to families 18 and 19, respectively. Cucumber chitinase used the retaining mechanism as known for bacterial chitinases and hen egg white lysozyme for which the mechanism has been determined. In contrast, bean chitinase catalyzed the hydrolysis of chitooligosaccharides with overall inversion of anomeric configuration.

Catalysis↗

Serum fatty acids and the risk of coronary heart disease.

To examine the relation between serum fatty acids and coronary heart disease (CHD), the authors conducted a nested case-control study of 94 men with incident CHD and 94 men without incident CHD who were enrolled in the Usual Care group of the Multiple Risk Factor Intervention Trial between December 1973 and February 1976. After confirming the stability of the stored serum samples, the authors measured serum fatty acid levels by gas-liquid chromatography and examined their association with CHD. In all multivariate models, levels of the cholesterol ester saturated fatty acid palmitic acid (16:0) were directly associated with CHD risk (standardized odds ratio = 1.68; 95% confidence interval 1.10-2.55 in the model that adjusted for total plasma cholesterol level). Levels of the phospholipid omega-3 fatty acid docosapentaenoic acid (22:5) were inversely associated with CHD risk in the two multivariate models that controlled for the effects of total plasma cholesterol level or high density lipoprotein cholesterol to total plasma cholesterol ratio (standardized odds ratio = 0.58; 95% confidence interval 0.38-0.89 in the first model that controlled for total plasma cholesterol level). In contrast to the first two multivariate models, levels of the docosahexaenoic acid (22:6) were inversely associated with CHD risk in a third multivariate model that controlled for the effects of high density lipoprotein cholesterol to low density lipoprotein cholesterol ratio (standardized odds ratio = 0.57; 95% confidence interval 0.36-0.90). These findings are consistent with other evidence indicating that saturated fatty acids are directly correlated with CHD and that omega-3 polyunsaturated fatty acids are inversely correlated with CHD. Because these associations were present after adjustment for blood lipid levels, other mechanisms, such as a direct effect on blood clotting, may be involved.

Adult↗

Health behaviors and survival among middle-aged and older men and women in the NHANES I Epidemiologic Follow-up Study.

BACKGROUND: Since the 1960s there has been a decline in mortality rates for older U.S. adults, suggesting the importance of examining the role of prevention and health promotion in improving the health and survival of older adults. Epidemiologic studies of age and gender differences in the impact of health behaviors on survival for older U.S. adults are needed to provide information for intervention and health promotion efforts for older Americans. METHODS: We examined whether health behavior risk factors (smoking, drinking, physical activity, and body weight) for mortality vary by age and gender among 6,109 adults 45-74 years old in the National Health and Nutrition Examination Survey 1971-1975 (NHANES I) who were traced during the 1982-1984 NHANES I Follow-up Survey. RESULTS: For middle-aged men (45-54 years old) and for older men (65-74 years old), both smoking and nonrecreational physical activity were predictors of survival time. Additionally, for older men, drinking and low body mass index were associated with shorter survival time. Among women, there was less consistency of associations across age groups. As with men, nonrecreational physical activity and low body mass index were associated with shorter survival among older women. CONCLUSIONS: These findings suggest that health behaviors are associated with survival in older adults as well as in middle-aged adults, although the specific behavioral risk factors may vary by age and gender.

Adult↗

Long-term physical functioning in persons with knee osteoarthritis from NHANES. I: Effects of comorbid medical conditions.

This study examined the effects of comorbid medical conditions (heart disease, pulmonary disease, hypertension and obesity) on the association of radiographic knee osteoarthritis (OA) with long-term difficulty in physical function. Data are from the National Health and Nutrition Examination Survey, 1971-1975 (NHANES I), a prospective epidemiologic cohort study, and the NHANES Epidemiologic Follow-up Study, 1982-1984 (NHEFS) and included 4059 persons who were 45-74 years old and participated in the detailed examination component of NHANES I. Knee OA was ascertained by anterior-posterior bilateral radiographs of the knee and self-report of knee pain, heart and pulmonary disease by self report of disease or symptoms, and hypertension and obesity by blood pressure and weight measurements. The presence of symptomatic knee OA at NHANES I was associated with reported difficulty at NHEFS 1982-84 in functions which used the lower extremity (ambulation and transfer). The presence of coexistent chronic conditions, particularly heart disease, pulmonary disease and obesity, increased the likelihood of subsequent disability. These findings suggest that knee OA is associated with long-term physical disability, and that the presence of coexistent chronic disease may increase the amount of long-term disability from knee OA.

Activities of Daily Living↗

Mutation analysis of the C-terminal vacuolar targeting peptide of tobacco chitinase: low specificity of the sorting system, and gradual transition between intracellular retention and secretion into the extracellular space.

The C-terminal propeptide of tobacco (Nicotiana tabacum) chitinase A has been shown to be necessary and sufficient for targeting of chitinases to the plant vacuole. The sequence specificity of this vacuolar targeting peptide (VTP) has now been analysed using transient expression of chitinases in Nicotiana plumbaginifolia protoplasts. An extracellular cucumber chitinase, previously used as a secreted reporter protein in transgenic tobacco, was also secreted into the incubation medium by the transiently transformed protoplasts. Addition of six to seven amino acids at the C-terminus to generate the VTP of tobacco chitinase A were sufficient to cause retention of most of the cucumber chitinase within the protoplasts. The chitinase A itself, as well as a mutant lacking the N-terminal chitin-binding domain, were retained to 80% in the protoplasts when low concentrations of the plasmid were used in the transient expression system. At high concentrations of plasmid, causing high levels of transiently expressed chitinase, retention was reduced, indicating saturation of the sorting system. Deletion of the C-terminal methionine did not affect the intracellular location, but deletion of even a single internal amino acid of the VTP caused predominantly secretion of tobacco chitinase A. In contrast, exchanges of amino acids in the VTP as well as substitution of the VTP with random sequences had intermediary effects that covered the whole range from retention to secretion. The results suggest that the sorting system responsible for the diversion of secretory proteins to the vacuole has a low specificity for the sequence of C-terminal targeting peptides, and that sequence changes in the VTP allow a gradual transition from vacuolar retention to secretion.

Amino Acid Sequence↗

Physiological compensation in antisense transformants: specific induction of an "ersatz" glucan endo-1,3-beta-glucosidase in plants infected with necrotizing viruses.

Plant class I glucan endo-1,3-beta-glucosidases (beta-1,3-glucanase; 1,3-beta-D-glucan glucanohydrolase, EC 3.2.1.39) have been implicated in development and defense against pathogen attack. Nevertheless, beta-1,3-glucanase deficiencies generated by antisense transformation of Nicotiana sylvestris and tobacco have little biological effect. We report here that another beta-1,3-glucanase activity is induced in these deficient mutants after infection with necrotizing viruses. Induction of class I beta-1,3-glucanase was markedly inhibited in leaves of N. sylvestris and tobacco antisense transformants infected with tobacco necrosis virus and tobacco mosaic virus, respectively. A serologically distinct beta-1,3-glucanase activity was present in the infected antisense transformants but was absent in both healthy and infected control plants and in antisense transformants treated with the stress hormone ethylene. Immunoblot analyses, localization studies, and measurements of antibody specificity indicate that this compensatory beta-1,3-glucanase activity is an intracellular enzyme different from known tobacco beta-1,3-glucanases. Therefore, plants can compensate for a deficiency in enzyme activity by producing a functionally equivalent replacement--i.e., "ersatz"--protein or proteins. The fact that compensation for beta-1,3-glucanase activity occurs in response to infection argues strongly for an important role of these enzymes in pathogenesis.

Cell Transformation, Viral↗

Design effects for binary regression models fitted to dependent data.

Dependent data, such as arise with cluster sampling, typically yield variances of parameter estimates which are larger than would be provided by a simple random sample of the same size. This variance inflation factor is called the design effect of the estimator. Design effects have been derived for cluster sampling designs using simple estimators such as means and proportions, and also for linear regression coefficient estimators. In this paper, we show that a method to derive design effects for linear regression estimators extends to generalized linear models for binary responses. In particular, some simple expressions for design effects in the linear regression model provide accurate approximations for binary regression models such as those based on the logistic, probit and complementary log-log links. We corroborate our findings with two examples and some simulation studies.

Acquired Immunodeficiency Syndrome↗

Robust inference for multivariate survival data.

Multivariate survival data arise when an individual records multiple survival events or when individuals recording single survival events are grouped into clusters. In this paper we propose a new method for the analysis of multivariate survival data. The technique is a synthesis of the Poisson regression formulation for univariate censored survival analysis and the generalized estimating equation approach for obtaining valid variance estimates for generalized linear models in the presence of clustering. When the survival data are clustered, combining the methods provides not only valid estimates for the variances of regression parameters but also estimates of the dependence between survival times. The approach entails specifying parametric models for the marginal hazards and a dependence structure, but does not require specification of the joint multivariate survival distribution. Properties of the methodology are investigated by simulation and through an illustrative example.

Humans↗

Posttranslational processing of a new class of hydroxyproline-containing proteins. Prolyl hydroxylation and C-terminal cleavage of tobacco (Nicotiana tabacum) vacuolar chitinase.

The fungicidal class I chitinases (EC 3.2.1.14) are believed to be important in defending plants against microbial pathogens. The vacuolar isoforms of tobacco (Nicotiana tabacum), chitinases A and B, are the first examples of a new type of hydroxyproline-containing protein with intracellular location, enzymic activity, and a small number of hydroxyprolyl residues restricted to a single, short peptide sequence. We have investigated the posttranslational processing and intracellular transport of transgene-encoded chitinase A in callus cultures of Nicotiana tabacum L. cv Havana 425 and leaves of Nicotiana sylvestris Spegazzini and Comes. Pulse-chase experiments and cell fractionation show that chitinase A is processed in two distinct steps. In the first step, the nascent protein undergoes an increase in apparent M(r) of approximately 1500 detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Experiments with the inhibitor of prolyl hydroxylation, alpha,alpha'-dipyridyl, and pulse-chase labeling of cells expressing recombinant forms of chitinase A indicate that the anomalous increase in M(r) is due to hydroxylation of prolyl residues. This step occurs in the endomembrane system before sorting for secretion and vacuolar transport and does not appear to be required for correct targeting of chitinase A to the vacuole. The second step is a proteolytic cleavage. Sequencing of tryptic peptides of the mature proteins indicates that during processing essentially all molecules of chitinase A and B lose a C-terminal heptapeptide, which has been shown to be a vacuolar targeting signal. This appears to occur primarily in the endomembrane system late in intracellular transport. A model for the posttranslational modification of chitinase A is proposed.

Amino Acid Sequence↗

The N-terminal cysteine-rich domain of tobacco class I chitinase is essential for chitin binding but not for catalytic or antifungal activity.

The vacuolar chitinases of class I possess an N-terminal cysteine-rich domain homologous to hevein and chitin-binding lectins such as wheat germ agglutinin and Urtica dioica lectin. To investigate the significance of this domain for the biochemical and functional characteristics of chitinase, chimeric genes encoding the basic chitinase A of tobacco (Nicotiana tabacum) with and without this domain were constructed and constitutively expressed in transgenic Nicotiana sylvestris. The chitinases were subsequently isolated and purified to homogeneity from the transgenic plants. Chromatography on colloidal chitin revealed that only the form with the N-terminal domain, and not the one without it, had chitin-binding properties, demonstrating directly that the domain is a chitin-binding domain (CBD). Under standard assay conditions with radioactive colloidal chitin, both forms of chitinase had approximately the same catalytic activity. However, kinetic analysis demonstrated that the enzyme without CBD had a considerably lower apparent affinity for its substrate. The pH and temperature optima of the two chitinases were similar, but the form with the CBD had an approximately 3-fold higher activation energy and retained a higher activity at low pH values. Both chitinases were capable of inhibiting growth of Trichoderma viride, although the form with the CBD was about three times more effective than the one without it. Thus, the CBD is not necessary for catalytic or antifungal activity of chitinase.

Antifungal Agents↗

Estimation efficiency and tests of covariate effects with clustered binary data.

Several approaches have been proposed to analyze clustered binary data, which arise in fields such as teratology and ophthalmology. These methods include mixed-effects and quasi-likelihood approaches, as well as models that use cluster responses as covariates. The three approaches measure different effects of covariates on binary responses, but simple approximations relate the magnitudes of their parameters. In this article, we present approximations to relate the standard errors of model parameters and Wald tests for covariate effects obtained from the different approaches. These approximations show that Wald tests involving cluster-level covariates will be approximately equivalent using the different approaches. However, approaches that model intracluster correlation, such as the mixed-effects model, provide more powerful tests of within-cluster covariates than those that do not model the correlation. Simulations and example data illustrate these findings.

Analysis of Variance↗

Vacuolar chitinases of tobacco: a new class of hydroxyproline-containing proteins.

The fungicidal type I chitinases contribute to the defense response of plants against pathogens. Two tobacco chitinases represent a different class of hydroxyproline-containing proteins. Hydroxyproline-rich proteins are predominantly extracellular, structural glycoproteins proteins that lack enzymatic activity and contain many hydroxyproline residues. In contrast, type I chitinases are vacuolar enzymes. They are not glycosylated and contain a small number of hydroxyproline residues restricted to a single, short peptide sequence.

Amino Acid Sequence↗

An annotated bibliography of methods for analysing correlated categorical data.

This paper provides an annotated bibliography of over 100 articles concerning methods for analysing correlated categorical response data. Most of the papers listed here concern categorical regression models and estimation, with particular emphasis on binary responses. The papers are classified by several characteristics which group them according to common themes. The bibliography serves as a reference of methods for analysts of correlated categorical data, as well as for persons interested in methodologic work in this active area of statistical research.

Clinical Trials as Topic↗

Cloning and disruption of a gene required for growth on acetate but not on ethanol: the acetyl-coenzyme A synthetase gene of Saccharomyces cerevisiae.

A DNA fragment of Saccharomyces cerevisiae with high homology to the acetyl-coenzyme A (acetyl-CoA) synthetase genes of Aspergillus nidulans and Neurospora crassa has been cloned, sequenced and mapped to chromosome I. It contains an open reading frame of 2139 nucleotides, encoding a predicted gene product of 79.2 kDa. In contrast to its ascomycete homologs, there are no introns in the coding sequence. The first ATG codon of the open reading frame is in an unusual context for a translational start site, while the next ATG, 24 codons downstream, is in a more conventional context. Possible implications of two alternative translational start sites for the cellular localization of the enzyme are discussed. A stable mutant of this gene, obtained by the gene disruption technique, had the same low basal activity of acetyl-CoA synthetase as wild-type cells when grown on glucose but completely lacked the strong increase in activity upon entering the stationary phase, providing direct proof that the gene encodes an inducible acetyl-CoA synthetase (ACS1) of yeast. As expected, the mutant was unable to grow on acetate as sole carbon source. Nevertheless, it showed normal induction of isocitrate lyase on acetate media, indicating that activity of acetyl-CoA synthetase is dispensable for induction of the glyoxylate cycle in S. cerevisiae. Surprisingly, disruption of the ACS1 gene did not affect growth on media containing ethanol as the sole carbon source, demonstrating that there are alternative pathways leading to acetyl-CoA under these conditions.

Acetate-CoA Ligase↗