Cholesteryl ester transfer protein gene polymorphism is a determinant of HDL cholesterol and of the lipoprotein response to a lipid-lowering diet in type 1 diabetes

The TaqIB cholesteryl ester transfer protein (CETP) gene polymorphism (B1B2) is a determinant of HDL cholesterol in nondiabetic populations. Remarkably, this gene effect appears to be modified by environmental factors. We evaluated the effect of this polymorphism on HDL cholesterol levels and on the lipoprotein response to a linoleic acid-enriched, low-cholesterol diet in patients with type 1 diabetes. In 44 consecutive type 1 diabetic patients (35 men), CETP polymorphism, apolipoprotein (apo) E genotype, serum lipoproteins, serum CETP activity (measured with an exogenous substrate assay, n = 30), clinical variables, and a diet history were documented. The 1-year response to diet was assessed in 14 type 1 diabetic patients, including 6 B1B1 and 6 B1B2 individuals. HDL cholesterol was higher in 10 B2B2 than in 14 B1B1 homozygotes (1.63 +/- 0.38 vs. 1.24 +/- 0.23 mmol/l, P < 0.01). HDL cholesterol, adjusted for triglycerides and smoking, was 0.19 mmol/l higher for each B2 allele present. CETP activity levels were not significantly different between CETP genotypes. Multiple regression analysis showed that VLDL + LDL cholesterol was associated with dietary polyunsaturated:saturated fatty acids ratio (P < 0.02) and total fat intake (P < 0.05) in the B1B1 homozygotes only and tended to be related to the presence of the apo E4 allele (P < 0.10). In response to diet, VLDL + LDL cholesterol fell (P < 0.05) and HDL cholesterol remained unchanged in 6 B1B1 homozygotes. In contrast, VLDL + LDL cholesterol was unaltered and HDL cholesterol decreased (P < 0.05) in 6 B1B2 heterozygotes (P < 0.05 for difference in change in VLDL + LDL/HDL cholesterol ratio). This difference in response was unrelated to the apo E genotype. Thus, the TaqIB CETP gene polymorphism is a strong determinant of HDL cholesterol in type 1 diabetes. This gene effect is unlikely to be explained by a major influence on the serum level of CETP activity, as an indirect measure of CETP mass. Our preliminary data suggest that this polymorphism may be a marker of the lipoprotein response to dietary intervention.     

A population study of the natural history of Wolff-Parkinson-White syndrome in Olmsted County, Minnesota, 1953-1989

BACKGROUND: Virtually all natural history studies of Wolff-Parkinson-White (WPW) syndrome have been case series and, as such, have been constrained by referral biases, skewed age and sex distributions, or brief follow-up periods. The purpose of our study was to examine the natural history, the development of arrhythmias, and the incidence of sudden death in an entire cohort of pediatric and adult WPW patients from a community-based local population. METHODS AND RESULTS: We identified 113 residents of Olmsted County, Minnesota, during the period 1953-1989 using the centralized records-linkage system provided by the Mayo Clinic and the Rochester Epidemiology Program Project. Medical records and ECGs were reviewed to confirm the diagnosis and to establish pathway location by ECG criteria. Follow-up, via record review and telephone interview, was complete in 95% of subjects through 1990. The incidence of newly diagnosed cases was approximately four per 100,000 per year. Preexcitation was not present on the initial ECG of 22% of the cohort. Approximately 50% of the population was asymptomatic at diagnosis, with 30% subsequently having symptoms related to arrhythmia at follow-up. Two sudden cardiac deaths (SCD) occurred over 1,338 patient-years of follow-up, yielding an overall SCD rate of 0.0015 (95% confidence interval, 0.0002-0.0054) per patient-year. No SCD occurred in patients asymptomatic at diagnosis. CONCLUSIONS: The incidence of sudden death in a local community-based population is low and suggests that electrophysiological testing should not be performed routinely in asymptomatic patients with WPW syndrome. Nevertheless, young, asymptomatic patients, particularly those < 40 years old, should return for medical follow-up should symptoms develop.     

Comparative severity of respiratory lesions of sialodacryoadenitis virus and Sendai virus infections in LEW and F344 rats

In several chronic diseases, lesions are more severe in LEW rats than in F344 rats. To determine whether or not acute viral diseases also are more severe in LEW rats than in F344 rats, we inoculated 6-7-week-old LEW and F344 rats with 10(7.2) cell culture infective units of sialodacryoadenitis virus or 10(4.7) infective units of Sendai virus. Twenty-four rats of each strain were given each virus. Lesions in nasal passages, tracheas, intrapulmonary airways, and pulmonary alveoli in 6 or 12 rats inoculated with each virus were assessed by scoring 5, 10, and 14 days after inoculation. Both viruses caused typical patchy necrotizing rhinitis, tracheitis, bronchitis, and bronchiolitis, with multifocal pneumonitis, in rats of both strains. Mean lesion indices for LEW rats given sialodacryoadenitis virus were significantly different from those for F344 rats for nasal passages on days 10 (0.999 vs. 0.680) and 14 (0.736 vs. 0.278), bronchi on day 5 (0.479 vs. 0.361), and alveoli on day 5 (0.677 vs. 0.275). Lesion indices for LEW rats given Sendai virus were significantly different from those for F344 rats for nasal passages on days 10 (1.000 vs. 0.611) and 14 (0.778 vs. 0.583); trachea on day 10 (0.625 vs. 0.028); bronchi on days 5 (0.476 vs. 0.331), 10 (0.123 vs. 0.013), and 14 (0.038 vs. 0); and alveoli on days 5 (0.413 vs. 0.114) and 10 (0.185 vs. 0.020). Thus, at the tested doses, both viruses caused more severe respiratory tract lesions in LEW rats than in F344 rats.     

Caged ATP-fuel for bionanodevices

Micro- and nanodevices require the controlled delivery of energy to power a variety of processes. The current paradigm of connecting a miniaturized device to a set of macroscopic auxiliary devices, such as power supplies or pumps, for the delivery of electrical and mechanical energy needs to be replaced to enable the design of stand-alone integrated bionanodevices with applications in remote biosensing or nanomedicine. Biological nanomachines, such as the motor protein kinesin, can efficiently convert energy stored in chemical compounds, in particular adenosine 5'-triphosphate (ATP), into mechanical work. This ability is an attractive feature of hybrid devices powered by biomolecular motors, since it removes the need for the storage and conversion of electrical energy. The consequences are a simplified fabrication process and packaging, leading to higher yields and lower costs, and the broadening of the applications, which can now include field-deployable nanodevices. Here, the potential of caged ATP as fuel for such engineering applications is discussed. Caged ATP can be stored in the buffer solution of a bionanodevice, "uncaged" by UV light, and utilized as fuel by many enzymes to catalyze chemical changes or power active transport. We demonstrate that DMNPE-caged ATP can be stored in sufficient amounts in a typical device and that the activation can be triggered with a UV lamp or even sunlight.     

Influence of dietary sodium bicarbonate on the potassium metabolism of growing dairy calves.

We evaluated the influence of supplemental dietary NaHCO3 on K metabolism of young dairy calves. Thirty-two Holstein and Jersey male and female calves were blocked at 56 to 70 d after birth according to breed, sex, and age and assigned randomly to a 2 x 2 factorial arrangement of dietary treatments for 8 wk: .4% K with 0% NaHCO3, .4% K with 2% NaHCO3, .6% K with 0% NaHCO3, and .6% K with 2% NaHCO3. Feed intake was not affected by dietary KCl or NaHCO3 supplementation, but average daily gain increased with increased K and tended to be reduced by dietary NaHCO3. Plasma K was elevated by increased dietary K but generally was unaffected by NaHCO3. Urinary Ca excretion appeared to be reduced by NaHCO3; urine pH increased with supplemental NaHCO3. Results indicate 1) the K requirement of the growing calf is between .40 and .55% of diet DM, 2) because urinary K excretion was elevated by dietary NaHCO3, the K requirement may be increased when the diet is supplemented with NaHCO3, and 3) average daily gain and plasma K are sensitive indicators of dietary K in the growing calf.     

Tolerance space and molecular similarity

Molecular similarity methods were used in selecting K nearest neighbors and in estimating mutagenicity of 95 aromatic amines and boiling points of a large set of over 2,900 compounds. Similarity is analyzed in terms of the concept of tolerance space. Specifically, the role of non-transitivity of the tolerance relation in estimating properties using similarity methods is examined.     

A classification for incidents and accidents in the health-care system

Problems that arise from health-care management, rather than from a disease process, are now recognized as making a substantial contribution to patient morbidity and mortality and to the cost of health care. However, most classifications of these problems do not provide sufficient detail to allow comparisons or to develop better strategies for the prevention, detection and management of these problems. A 'Generic Occurrence Classification' was developed to record their salient features, place them in context and elicit any system or human error-based contributing factors. This was done by an iterative process in which 'natural categories', identified from over 2000 incidents and 800 adverse events, were placed in a hierarchical structure created using software written in Microsoft Visual Basic; data were stored in a Microsoft Access database. This was shown to be a valid and reliable way to compare incidents and accidents from different sources and to allow sufficient detail to be retrieved to develop preventive strategies.