Age of onset of drug use and its association with DSM-IV drug abuse and dependence: results from the National Longitudinal Alcohol Epidemiologic Survey

Although adaptive explanations for menstruation go back at least twenty-five hundred years, in the last decade two new hypotheses have been advanced. The first suggests that menstruation evolved to cleanse the uterus of pathogens introduced by sperm, and the second argues that the function of endometrial regression (with the associated menstruation in humans) is to save energy by getting rid of tissue, rather than maintaining it in the absence of an available blastocyst. Both these suggestions may be questioned on the grounds that they do not take into account the physiology of the reproductive processes involved. Menstruation is not an independent physiological process and is unlikely to have been selected for independently of the evolutionary events that led to it. Furthermore, most primitive menstruating animals would have menstruated infrequently, and many may have reproduced or died without ever menstruating. In order to provide a context for understanding how menstruation may have come about, the evolution of the female vertebrate reproductive tract is briefly reviewed. In later stages, the coevolution of the embryo and uterus resulted in an intimate association between the trophoblast and the uterine blood vessels. As the embryo became more invasive, the uterus responded with increased cellular growth and differentiation of the endometrium to accommodate it. This reached its peak in mammals (such as rodents and humans), where the embryo passes through the epithelium into the endometrial stroma, which responds with differentiation of cells and blood vessels. Progesterone, secreted after ovulation, plays a crucial role in preparation for pregnancy. In addition to its well-known effects on the uterus, progesterone may be important in suppressing the inflammatory reaction that would be expected in response to the presence of a foreign body, such as an embryo. It is also suggested that vascular and cellular differentiation of the endometrial stroma has evolved by adaptation of the inflammatory (granulation tissue) reaction. When progesterone levels fall at the end of the cycle, there is tissue breakdown and bleeding. The uterus then reforms for the next ovulatory cycle. It is shown that the female reproductive tract has multiple functions that must occur in sequence. The coevolution of the embryo and maternal tract thus led to the close contact of two genetically different tissues, and problems such as the inflammatory reaction had to be overcome. Menstruation is a necessary consequence of these evolutionary changes, and needed no adaptive value in order to evolve.     

Reduction of triceps muscle force after shortening of the distal humerus: a computational model

A retrospective case reference study examining the use of alcohol and tobacco in 303 women aged 40 or over suffering from oral or oropharyngeal cancer was conducted in the south-west Netherlands. Both alcohol and tobacco consumption are important in the development of oral and oropharyngeal cancer with increased consumption of both markedly increasing the risks of cancer, but alcohol having the greater effect.     

Performance under capitation: the true cost of infrastructure

Administrative costs are a major item of concern for capitated provider groups, who must maintain a sophisticated infrastructure to allow them to manage and deliver clinical care to their patients under a fixed budget. The cost of this infrastructure is under steady upward pressure, as HMOs delegate more activities to providers and step up their reporting requirements. Our experience in establishing an infrastructure for a provider network is reported, and indicates substantial costs for both start-up and ongoing operations, which are highly volume dependent. A powerful case exists in favor of centralizing and pooling administrative infrastructure across related provider groups.     

Mapping Escherichia coli elongation factor Tu residues involved in binding of aminoacyl-tRNA

Two residues of Escherichia coli elongation factor Tu involved in binding of aminoacyl-tRNA were identified and subjected to mutational analysis. Lys-89 and Asn-90 were each replaced by either Ala or Glu. The four single mutants were denoted K89A, K89E, N90A, and N90E, respectively. The mutants were characterized with respect to thermal and chemical stability, GTPase activity, tRNA affinity, and activity in an in vitro translation assay. Most conspicuously tRNA affinities were reduced for all mutants. The results verify our structural analysis of elongation factor Tu in complex with aminoacyl-tRNA, which suggested an important role of Lys-89 and Asn-90 in tRNA binding. Furthermore, our results indicate helix B to be an important target site for nucleotide exchange factor EF-Ts. Also the mutants His-66 to Ala and His-118 to either Ala or Glu were characterized in an in vitro translation assay. Their functional roles are discussed in relation to the structure of elongation factor Tu in complex with aminoacyl-tRNA.     

Codistribution of procathepsin B and mature cathepsin B forms in human prostate tumors detected by confocal and immunofluorescence microscopy

Ascorbic acid can recycle alpha-tocopherol from the tocopheroxyl free radical in lipid bilayers and in micelles, but such recycling has not been demonstrated to occur across cell membranes. In this work the ability of intracellular ascorbate to protect and to recycle alpha-tocopherol in intact human erythrocytes and erythrocyte ghosts was investigated. In erythrocytes that were 80% depleted of intracellular ascorbate by treatment with the nitroxide Tempol, both 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) and ferricyanide oxidized alpha-tocopherol to a greater extent than in cells not depleted of ascorbate. In contrast, in erythrocytes in which the intracellular ascorbate concentration had been increased by loading with dehydroascorbate, loss of alpha-tocopherol was less with both oxidants than in control cells. Protection against AAPH-induced oxidation of alpha-tocopherol was not prevented by extracellular ascorbate oxidase, indicating that the protection was due to intracellular and not to extracellular ascorbate. Incubation of erythrocytes with lecithin liposomes also generated an oxidant stress, which caused lipid peroxidation in the liposomes and depleted erythrocyte alpha-tocopherol, leading to hemolysis. Ascorbate loading of the erythrocytes delayed liposome oxidation and decreased loss of alpha-tocopherol from both cells and from alpha-tocopherol-loaded liposomes. When erythrocyte ghosts were resealed to contain ascorbate and challenged with free radicals generated by AAPH outside the ghosts, intravesicular ascorbate was totally depleted over 1 h of incubation, whereas alpha-tocopherol decreased only after ascorbate was substantially oxidized. These results suggest that ascorbate within the erythrocyte protects alpha-tocopherol in the cell membrane by a direct recycling mechanism.     

A twin and family study of the association between immune system dysfunction and dyslexia using blood serum immunoassay and survey data

We conducted a study of the association between developmental reading disability (DRD) and immune disorders (ID) using both survey and immunoassay data in two separate samples of families. One sample was made up of twins and their parents and was ascertained through a population-based sampling scheme. The other sample was a set of extended pedigrees selected for apparent autosomal dominant transmission of DRD. We failed to find an association between DRD and ID in either sample, regardless of the method used to assess immune system function. Even though our twin sample provided evidence that both DRD and immune conditions were significantly heritable, there was no evidence for a genetic correlation between ID and DRD nor was there any clear indication that a special subgroup of individuals may be comorbid for these conditions because of genetic reasons. How these negative findings can be reconciled with the developmental hypothesis of Geschwind, Behan, Galaburda, and colleagues, and how they may relate to the gene locus influencing DRD that has been recently located in the HLA region of the short arm of chromosome 6 is discussed.     

Potential antitumor agents. 19. Multiply substituted 4'-(9-acridinylamino)methanesulfonanilides

A series of 42 multiply substituted 4'-(9-acridinylamino)methanesulfonanilides has been prepared and evaluated in the L1210 system. In addition to biologic activity changes resulting from altered agent lipophilic-hydrophilic balance variants containing both acridine 4-CH3 and 3-NH2, NHCOCH3 or NO2 substituents have reduced activity. Variants 3,6-disubstituted, using functions of differing electronic character, have depressed activity, suggesting that there is limited site bulk tolerance. Asymmetric 3,5-disubstitution should then be the preferred pattern; the 3-ND-5CH-3'-OCH variant is the most dose potent (optimum dose qd 1-5, 1.25 mg/kg/day) of the high activity agents of this series so far prepared.     

Functional longevity of intraperioneal drains: an experimental evaluation

Various types of drains were inserted into the peritoneal cavity of twenty-eight dogs. After one to seven days, all drains failed to show the presence of 200 cc of colored fluid injected intraperitoneally. On autopsy, all tubes were surrounded and occluded by omentum.