A study of caloric restriction and cardiovascular aging in cynomolgus monkeys (Macaca fascicularis): a potential model for aging research

Caloric restriction has been demonstrated to retard aging processes and extend maximal life span in rodents, and is currently being evaluated in several nonhuman primate trials. We initiated a study in 32 adult cynomolgus monkeys to evaluate the effect of caloric restriction on parameters contributing to atherosclerosis extent. Following pretrial determinations, at which time a baseline measure of ad libitum (ad lib) dietary intake was assessed, animals were randomized to an ad lib fed group (control) or a caloric restriction group (30% reduction from baseline intake). The animals are being evaluated for glycated proteins, insulin, glucose, insulin sensitivity measures, and specific measures of body fat composition by CT scans (e.g., intra-abdominal fat) over specified intervals. The results from the first year of observation demonstrate a significant diet effect on body weight, and specifically intra-abdominal fat. Further, insulin sensitivity has been significantly increased after 1 year of caloric restriction compared to the ad lib fed group. These studies indicate that caloric restriction has a marked effect on a pathologic fat depot, and this change is associated significantly with an improvement in peripheral tissue insulin sensitivity.     

Human immunodeficiency virus type 1 may preferentially integrate into chromatin occupied by L1Hs repetitive elements

Human DNA flanking sites of eight human immunodeficiency virus type 1 (HIV-1) proviral integrations have been analyzed in isolates derived both from integrations in an infected individual and from tissue culture. Sequence analysis encompassing 80-3000 bp of human DNA on one or both sides of the site of integration revealed that seven of the eight HIV-1 proviruses had integrated directly into or within one nucleosome's distance from an L1Hs or Alu repetitive element. To compare this with the frequency at which human L1 or Alu elements sharing > or = 70% identity with L1Hs and Alu consensus sequences would be encountered at random, > 200 bp from each of 82 individual anonymously cloned segments of human DNA were sequenced: L1Hs elements were encountered in 8.5% of the 82 clones and Alu elements were encountered in 13.4+ by using these homology windows. From these data it appears that HIV-1 integrates into or near L1Hs elements with an approximately 6-fold higher frequency than would be expected if HIV-1 integration events were distributed uniformly throughout the genome. A cumulative binomial probability test shows that there is a 0.26% chance that one would arrive at these figures by chance and puts the data well within a 99% confidence interval. We propose that sites of L1Hs and Alu insertions originally occurred in regions of chromatin that were more easily accessible to the retroposon machinery and that these regions are now acting as preferred integration sites for HIV-1.     

Form and objective of the decision rule in absolute identification

In several conditions of a line length identification experiment, the subjects' decision making strategies were systematically biased against the responses on the edges of the stimulus range. When the range and number of the stimuli were small, the bias caused the percentage of correct responses to be highest in the center and lowest on the extremes of the range. Two general classes of decision rules that would explain these results are considered. The first class assumes that subjects intend to adopt an optimal decision rule, but systematically misrepresent one or more parameters of the decision making context. The second class assumes that subjects use a different measure of performance than the one assumed by the experimenter: instead of maximizing the chances of a correct response, the subject attempts to minimize the expected size of the response error (a "fidelity criterion"). In a second experiment, extended experience and feedback did not diminish the bias effect, but explicitly penalizing all response errors equally, regardless of their size, did reduce or eliminate it in some subjects. Both results favor the fidelity criterion over the optimal rule.     

Uncinate processes and Luschka joints influence the biomechanics of the cervical spine: quantification using a finite element model of the C5-C6 segment

Demonstration and quantification of site-specific intracoronary administration of pharmacological compounds has been limited thus far to animal experimental models. Recently, a method applicable in humans has been developed. The aim of this study is to give an overview on the available methods to visualize and quantify intravascularly administered "labeled" drugs in animals and to describe the historical development of a method now applied in the clinical arena. The potential of this approach is briefly summarized.     

A comparison of spectral and physicochemical properties of yeast iso-1 cytochrome c and Cys 102-modified derivatives of the protein

Derivatives of yeast iso-1 cytochrome c, chemically modified at Cys-102 (Cys-102 acetamide-derivatized monomer, Cys-102 thionitrobenzoate-derivatized monomer, Cys-102 S-methylated monomer, and the disulfide dimer), exhibit different spectral and physicochemical properties relative to the native, unmodified protein, depending on the nature of the modifying group. The results of proton NMR studies on the Cys-102 acetamide-derivatized monomer of iso-1 ferricytochrome c indicate that the conformational characteristics of the heme environment in this protein derivative are intermediate between those of the unmodified monomer and disulfide dimer forms of the protein. Measurements of the pKa of the alkaline transitions of the five forms of iso-1 ferricytochrome c provided values of 8.89, 8.82, 8.67, 8.47, and 8.50 for the unmodified monomer, S-methylated monomer, acetamide-derivatized monomer, thionitrobenzoate-derivatized monomer, and disulfide dimer, respectively. The results of proton NMR studies of the reduced form of these proteins suggest that the heme environments of the unmodified monomer and disulfide dimer derivatives of iso-1 ferrocytochrome c are similar and indicate that treatment of the thionitrobenzoate-derivatized and disulfide dimer forms of the protein with sodium dithionite results in cleavage of the disulfide bonds at position 102. Circular dichroism studies reveal that only the disulfide dimer form of iso-1 ferricytochrome c exhibits a Soret CD spectrum which differs from the native, unmodified monomer in that the intensity of the negative band at approximately 420 nm is diminished in the spectrum of the dimer relative to the spectrum of the monomer. Soret CD spectra of the ascorbate-reduced form of all protein derivatives are similar. The process of "autoreduction" of yeast iso-1 ferricytochrome c is shown to occur in the absence of a free sulfhydryl group at position 102 and is exacerbated under moderately high pH conditions. These results are suggestive of the presence of a redox-active amino acid, perhaps a tyrosine, in yeast iso-1 cytochrome c.     

Selegiline and lymphocyte superoxide dismutase activities in Parkinson''s disease

Health care: public, private or both? In Great Britain, about 13% of the population is covered by private health insurance, and everyone else is served by the public health care system known as the National Health Service, or NHS. Caroline Richmond, who examined the impact of private medical practice in Britain, says people become private patients for one compelling reason: to avoid the NHS's notoriously long waiting lists for surgery. According to Professor Alan Maynard, a health care researcher, the mainstays of the private sector are the "three h's" --hips, hernias and hemorrhoids-- along with some elective surgery, particularly in gynecology and opthalmology. Another small sector focuses on fertility regulation and cosmetic surgery. Although the levels are not monitored closely, physician consultants are not permitted to earn more than 10% of their income from private practice.     

Extradural aneurysms

Extradural aneurysms have distinct characteristics from their intradural counterparts. Most extradural aneurysms cannot be treated by direct surgical exposure and clip ligation or by direct endovascular means without parent vessel sacrifice. Arterial occlusion with or without bypass grafting remains the traditional treatment. Controversy about the "best" or "proper" technique of arterial balloon test occlusion is rivaled only by that of the necessity for bypass grafting when apparent tolerance for arterial occlusion has been demonstrated.     

The synergy of low lung function and low body mass index predicting all-cause mortality among older Japanese-American men

OBJECTIVE: To assess the joint characteristics of low standardized weight and compromised pulmonary function in predicting all-cause mortality. DESIGN: A population-based, prospective cohort study. SETTING: Oahu Island, Hawaii. PARTICIPANTS: Surviving Japanese-American men of the Honolulu Heart Program cohort, 71 to 93 years of age (N = 3059). MEASUREMENTS: Body mass index (BMI-weight in kilograms/square of height in meters) and 1-second forced expiratory volume (FEV1) as a percentage of age- and height-predicted FEV1 from the 1991 to 1993 examination of the cohort. Mortality data derived from the ongoing tracking of deaths of the cohort. Relations of selected risk factors among joint levels of BMI (< or = 21, > 21 to < 25, > or = 25 kg/m2) and percent predicted FEV1 (< or = 70%, > 70%) were determined. The impact of these covariates on relations between joint BMI/percent predicted FEV1 levels and subsequent all-cause mortality was assessed. RESULTS: The highest age-adjusted mortality rate (91.9 deaths per 1000 person-years) was noted among men characterized by the joint conditions of percent predicted FEV1 < or = 70% and BMI < or = 21 kg/m2. This rate was 4.0 times the mortality rate of a "healthy" reference group characterized by percent predicted FEV1 > 70% and 21 < BMI < 25 kg/m2. This rate ratio is attenuated to 3.2 upon statistical control for measures of current and past smoking behavior. Among the three strata of BMI, statistical interaction is reflected in a heterogeneity of mortality rate differences (49.7, 21.8, -9.6 deaths/person-year, respectively) and rate ratios (2.18, 1.98, .66, respectively) comparing men with percent predicted FEV1 < or = 70% to > 70%. CONCLUSION: Joint loss of pulmonary function and relative weight is predictive of subsequent all-cause mortality in excess of additive or multiplicative effects of each condition separately. Smoking behavior may contribute to this observation.