Evidence for a recommended dietary allowance for vitamin C from pharmacokinetics: a comment and analysis

The current recommended dietary allowance (RDA) for vitamin C, as proposed by the Food and Nutrition Board/National Research Council in 1980 and reconfirmed in 1989, is 60 mg daily for nonsmoking adult males. Levine et al. [Levine, M., Conry-Cantilena, C., Wang, Y., Welch, R. W., Washko, P. W., et al. (1996) Proc. Natl. Acad. Sci. USA 93, 3704-3709], based on a study of vitamin C pharmacokinetics in seven healthy men, have now proposed that the RDA should be increased to 200 mg daily. I have examined, in brief, the experimental and conceptual bases for this new recommendation and its implications for public health and nutrition policy and programs. Using, for illustrative purposes only, data extracted from each of two recent dietary surveys of noninstitutionalized adult males living in households in the Netherlands and the United States, it is predicted that the prevalence of intakes inadequate to meet the individual's own requirement would be about 96% or 84%, respectively, if the criteria of adequacy used for derivation of the 200 mg RDA are accepted. Depending upon the particular average requirement value for ascorbic acid that might be derived from their data, the proposal by Levine et al. would mean a desirable increase in mean intakes in these two populations by as much about 2-to 3-fold. Hence, before an action of this kind is to be recommended, an answer must be sought to the question whether current experimental data including the criteria selected (saturation kinetics) are adequate to establish a new set of requirements for vitamin C, which then carry such profound policy implications. This will require critical assessment of all of the available evidence emerging from laboratory, clinical, and epidemiological studies to determine whether it provides a sufficient rationale for accepting criteria of vitamin C adequacy such as those proposed by Levine et al. and the requirement estimates so derived.     

Distribution of myosin heavy chain isoforms in non-weight-bearing rat soleus muscle fibers

The effects of 14 days of spaceflight (SF) or hindlimb suspension (HS) (Cosmos 2044) on myosin heavy chain (MHC) isoform content of the rat soleus muscle and single muscle fibers were determined. On the basis of electrophoretic analyses, there was a de novo synthesis of type IIx MHC but no change in either type I or IIa MHC isoform proportions after either SF or HS compared with controls. The percentage of fibers containing only type I MHC decreased by 26 and 23%, and the percentage of fibers with multiple MHCs increased from 6% in controls to 32% in HS and 34% in SF rats. Type IIx MHC was always found in combination with another MHC or combination of MHCs; i.e., no fibers contained type IIx MHC exclusively. These data suggest that the expression of the normal complement of MHC isoforms in the adult rat soleus muscle is dependent, in part, on normal weight bearing and that the absence of weight bearing induces a shift toward type IIx MHC protein expression in the preexisting type I and IIa fibers of the soleus.     

Comparative study of chronic aluminum-induced neurofilamentous aggregates with intracytoplasmic inclusions of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is characterized neuropathologically by chromatolysis, Bunina bodies, hyaline inclusions, skein-like inclusions and axonal spheroids. Aluminum, a known neurotoxin, is the cause of dialysis encephalopathy and is considered to be a causative agent in high incidence foci of ALS in the western Pacific. We have developed an experimental model of motor neuron degeneration in New Zealand white rabbits using chronic low-dose intracisternal administration of aluminum and compared the clinical and neuropathological changes to those of human ALS. Aluminum-inoculated rabbits developed progressive hyperreflexia, hypertonia, limb splaying, gait impairment, muscle wasting, hindlimb paralysis and impaired tonic immobility responses without overt encephalopathic features over a 14-month period. Examination of spinal cords from these animals demonstrated the frequent occurrence and progressive development of anterior horn cell lesions that included small, round, argentophilic perikaryal inclusions similar to hyaline inclusions seen in human ALS. Other inclusions were more condensed and eosinophilic, while still others had neurofibrillary tangle-like morphologies. Axonal spheroids and neuritic thickenings were also prominent and were identical to those seen in human ALS. We believe that the similar and progressive development of neuropathological changes observed in the chronic aluminum-intoxication model, compared to human ALS, warrants further study to aid in understanding the cellular and molecular mechanisms of human motor neuron disease.     

Study of correlations in DNA sequences

We present a method for unified statistical analysis of short and long range correlations between various nucleotides in genomic DNA strands. The approach is based on the mutual study of Fourier structure factor spectra and pair correlation functions. The analysis of cross correlations in the different ranges of structural spectra permits identification of the main sources of correlations, namely, the coherent point mutations, coincident periodicities or large scale density variations. The technique for assessment of structural coupling between various genes in the genome is also described.     

Angiographic analysis and results of endovascular therapy of aneurysm of vein of Galen

A computer program was developed in conjunction with a musculoskeletal modeling scheme to determine lower extremity joint angular velocity profiles which allow specific muscles, if activated tetanically, to generate their greatest power. As input the program requires subject anthropometric and joint configuration data. Muscle-tendon (MT) attachment location data and a straight line MT model are used to calculate MT lengths for each joint configuration. The shortening velocity which allows an active muscle to generate its greatest power is calculated based on muscle architecture and a relationship between power and shortening velocity. A finite difference technique is used to calculate the time between sequential joint configurations which will produce the optimal muscle shortening velocity. This time is then used to calculate optimal joint angular velocities for each muscle and and for each joint configuration. The utility of this program is demonstrated by calculating optimal joint angular velocities for fifteen muscles and comparing calculated knee extension velocities with experimental results cited in the literature.     

Dental caries in the deciduous teeth of the children from Gulbarga, Karnataka

A cross-sectional dental examination of 1,560 randomly selected unrelated children of Gulbarga, Karnataka has shown about 30% of the children with deciduous teeth suffering from one or more carious teeth. The proportion of male children with df teeth was larger than female ones; the difference between the two being statistically significant (chi 12 = 8.0387). Its incidence was higher in children of low income group. Muslims (36.2%) were found to be affected more than Hindus (29.6%) and Christians (27.8%). An increase in the frequency of carious children was observed with the increasing age excepting the children aged 12 years and above who have shown a decreasing trend. In both the sexes mandibular teeth were found more susceptible than maxillary ones. No side difference was found in either jaw. Lower second molars were affected more, followed by lower first and upper second molars. Toothwise prevalence of caries by age showed no consistent trend either in maxilla or mandible.     

A case-control study of menopausal estrogen therapy and breast cancer

The association between estrogen replacement therapy and female breast cancer was studied in two Los Angeles area retirement communities. The 138 study cases of breast cancer occurring in residents younger than 75 years were compared with age- and race-matched community control subjects. The risk ratio for a total cumulative dose in excess of 1,500 mg was estimated to be 2.5 in women with intact ovaries. This increase was present using various independent sources of drug usage information but was inconsistent at low dose and undetectable in oophorectomized women. No important sources of confounding could be identified, and no risk modifiers could be identified except for a history of surgically confirmed benign breast disease. In such women with intact ovaries, the risk ratio for a high cumulative dose rose to 5.7 relative to nonusers with normal breasts.     

ABSs系统模糊控制器优化设计

已经开发了的ABSs系统改善了突然制动和特别是滑动路面状况时车辆控制。这样的控制目标是在保持车辆合适稳定性及可操纵性和缩短车辆刹车距离情况下在要求的方向增大车轮的牵引力。本文提出了ABSs系统优化的模糊控制器。从保持其车轮滑动值为目标函数获得车轮最大的牵引力和车轮最大的减速度。采用遗传算法优化模糊系统的全部组件。采用误差数整体优化方法收敛接近最优点。仿真结果表明快速收敛和对不同路况的控制器的最好性能。     

Chimeric bispecific OC/TR monoclonal antibody mediates lysis of tumor cells expressing the folate-binding protein (MOv18) and displays decreased immunogenicity in patients

The current environment in which medicine is taught and practiced requires that medical schools pay increased attention to the faculty member's roles, rewards, career development, and productivity. Medical schools must make strategic decisions about the allocation of resources that can nurture their faculties and support the activities in academic and community settings in which faculty are involved. From 1993 to 1995 Allegheny University of the Health Sciences (formerly Medical College of Pennsylvania and Hahnemann University) designed a comprehensive system for the professional development of faculty. This system is based upon expanded categories of faculty academic activity and scholarship. New programs were implemented to reorient faculty toward conducting and documenting the expanded array of scholarly activities. The main characteristics of the new system are the establishment of formally defined performance expectations, the vertical alignment of the individual faculty member's objectives with the department's mission and the school's mission, and an increasing emphasis upon faculty interdependence, accountability, and use of sound business practices. The authors describe these and other aspects of the design of the new system in detail and report initial results and lessons learned from the system's implementation, evaluation, and dissemination throughout the university. The long-term success of this comprehensive professional development program will be assessed over time by observing how this institution advances its mission in a well-planned and cost-effective manner that retains talented, productive, and professionally fulfilled faculty.