BackgroundA systematic literature review was conducted to (a) identify the most frequently used health-related quality of life (HRQOL) models and (b) critique those models.MethodsOnline search engines were queried using pre-determined inclusion and exclusion criteria. We reviewed titles, abstracts, and then full-text articles for their relevance to this review. Then the most commonly used models were identified, reviewed in tables, and critiqued using published criteria.ResultsOf 1,602 titles identified, 100 articles from 21 countries met the inclusion criteria. The most frequently used HRQOL models were: Wilson and Cleary (16%), Ferrans and colleagues (4%), or World Health Organization (WHO) (5%). Ferrans and colleagues’ model was a revision of Wilson and Cleary’s model and appeared to have the greatest potential to guide future HRQOL research and practice.ConclusionsRecommendations are for researchers to use one of the three common HRQOL models unless there are compelling and clearly delineated reasons for creating new models. Disease-specific models can be derived from one of the three commonly used HRQOL models. We recommend Ferrans and colleagues’ model because they added individual and environmental characteristics to the popular Wilson and Cleary model to better explain HRQOL. Using a common HRQOL model across studies will promote a coherent body of evidence that will more quickly advance the science in the area of HRQOL.

The angiotensin-converting enzyme (ACE; EC 3.4.15.1) gene (Ace) encodes both a somatic isozyme found in blood and several other tissues, including the epididymis, and a testis-specific isozyme (testis ACE) found only in developing spermatids and mature sperm. We recently used gene targeting to disrupt the gene coding for both ACE isozymes in mice and reported that male homozygous mutants mate normally but have reduced fertility; the mutant females are fertile. Here we explore the male fertility defect. We demonstrate that ACE is important for achieving in vivo fertilization and that sperm from mice lacking both ACE isozymes show defects in transport within the oviducts and in binding to zonae pellucidae. Males generated by gene targeting that lack somatic ACE but retain testis ACE are normally fertile, establishing that somatic ACE in males is not essential for their fertility. Furthermore, male and female mice lacking angiotensinogen have normal fertility, indicating that angiotensin I is not a necessary substrate for testis ACE. Males heterozygous for the mutation inactivating both ACE isozymes sire wild-type and heterozygous offspring at an indistinguishable frequency, indicating no selection against sperm carrying the mutation.Angiotensin-converting enzyme (ACE; EC 3.4.15.1) catalyzes the cleavage of C-terminal dipeptides from several substrates including angiotensin I and bradykinin (1). The gene for ACE (ACE in humans, Ace in mice) codes for both a somatic and a smaller testis-specific isozyme. Somatic ACE is anchored to the plasma membranes of vascular endothelial cells and several epithelia, including cells in the epididymis, and a soluble form is present in blood. The testis isozyme is found only in developing spermatids and in mature sperm (2-5).Somatic ACE encoded by the entire gene is composed of two homologous amino acid domains (6, 7). The testis isozyme is encoded by the second half of the gene under the control of a testis-specific promoter located within intron 12 (8). The testis isozyme has a unique N-terminal sequence determined by a testis-specific exon; its remaining sequence is identical to the C-terminal domain of somatic ACE (9-11). Transcription of testis ACE in mouse spermatogenic cells begins in late pachytene spermatocytes (3) or after meiosis (4), and ACE protein is first detected in haploid spermatids (2-4). The tissue specificity of testis ACE is achieved with a promoter sequence of 91 base pairs (12). The functions of the ACE isozymes in male reproduction are unknown.We recently generated mice carrying an insertional disruption of exon 14 of the murine Ace gene, which prevents the synthesis of both testis and somatic ACE (13). Intercrossing of heterozygous mice gave Ϸ11% homozygous mutant mice compared with the expected 25%. Compared with wild-type mice (which we designate Ace ST ͞Ace ST , hereafter abbreviated STST to indicate the presence of both the somatic and testis isozymes), the homozygous mutant (stst) mice lacking both isozymes have blood pressures reduced about 3...

A cDNA clone encoding a putative glyceraldehyde 3-phosphate dehydrogenase (GAPD-S) protein specific to spermatogenic cells was isolated from a mouse spermatogenic cell expression library. The Gapd-s cDNA contained 1451 bp of transcribed sequence, including an ATG initiation codon and a poly(A) addition signal. The location of the Gapd-s initiation codon differed from that of other Gapd sequences, resulting in a germ cell GAPD-S protein predicted to contain 105 additional residues at the amino terminus. While GAPD is constitutively expressed in somatic tissues, Northern blot analysis demonstrated that a Gapd-s probe hybridized to a 1.5-kb transcript present only in the testis. The Gapd-s mRNA was first detected during postnatal development in the testes of 20-day-old mice, suggesting that gene expression begins shortly after the appearance of haploid round spermatids. Northern analysis of RNA from isolated mouse pachytene spermatocytes and spermatids confirmed that Gapd-s expression is confined to post-meiotic germ cells. GAPD has been previously proposed to be the key enzyme regulating glycolysis in isolated round spermatids. We hypothesize that the GAPD-S enzyme plays an important role in regulating the switch between different pathways for energy production during spermiogenesis and in the spermatozoon.

Fisher's geometrical model was introduced to study the phenotypic size of mutations contributing to adaptation. However, as pointed out by Haldane, the model involves a simplified picture of the action of natural selection, and this calls into question its generality. In particular, Fisher's model assumes that each trait contributes independently to fitness. Here, we show that Haldane's concerns may be incorporated into Fisher's model solely by allowing the intensity of selection to vary between traits. We further show that this generalization may be achieved by introducing a single, intuitively defined quantity that describes the phenotype prior to adaptation. Comparing the process of adaptation under the original and generalized models, we show that the generalization may bias results toward either larger or smaller mutations. The applicability of Fisher's model is then discussed. Keywords: geometrical model, beneficial mutations, adaptation.The classic arguments in favor of micromutationalismthe doctrine that mutations of very small phenotypic effect are the most likely to contribute to adaptation-are given by Fisher (1930). To support this position, Fisher offered an analogy, comparing the effect of a mutation to the "mechanical adaptation of an instrument, such as a microscope." He claimed that "it is sufficiently obvious that any large derangement will have a very small probability of improving the adjustment," while in the case of the smallest possible alterations, "the chance of improvement should be almost exactly half" (Fisher 1930, pp. 37-38). In addition to his verbal analogy, Fisher introduced a mathematical model of natural selection acting on multiple quantitative traits. In the model, each trait has an optimal value, and the fitness of a complete phenotype is jointly *

Positive- and negative-contrast stimuli yield the perceptions of brightness and darkness, respectively, and are processed separately by ON and OFF neural pathways. The properties of these morphologically and pharmacologically distinct subsystems were measured in humans by recording visual evoked potentials (VEPs). These electrical responses from the visual cortex were elicited by novel positive- and negative-contrast stimuli, designed to emphasize, selectively, contributions from ON and OFF pathways. Results revealed differential processing of the two types of contrast information, suggesting asymmetries in ON and OFF subsystems; OFF subsystems have finer spatial tuning and greater contrast gain than ON subsystems. These VEPs may be useful in diagnosing neurological disorders that involve primarily one subsystem.

Hemodialysis patients have difficulty self-managing a complex dietary and fluid regimen. The purpose of this feasibility study was to pilot test an electronic self-monitoring intervention based on social cognitive theory. During a six-week intervention, 24 participants self-monitored diet and fluid intake using the Dietary Intake Monitoring Application (DIMA), and 20 participants served as controls by monitoring their activity using the Daily Activity Monitor Application (DAMA). Results from this pilot study suggest the intervention is feasible and acceptable, although few significant effects on outcomes were found in this small sample. The DIMA has potential to facilitate dietary and fluid self-monitoring but requires additional refinement and further testing.

ABSTRACT:We previously established that levels of the sperm membrane protein, SP22, are highly correlated with the fertility of sperm from the cauda epididymidis of rats exposed to both epididymal and testicular toxicants, and that a testis-specific SP22 transcript is expressed in postmeiotic germ cells. In this study, polyclonal and monoclonal antibodies were generated to study the expression of SP22 in the testis and epididymis, and to determine whether SP22 plays a coincidental or causal role in fertility. Polyclonal antiserum was raised in sheep against full-length recombinant rat SP22 (rSP22) . Hybridoma clones were generated from mice immunized with rSP22 and boosted with native SP22; positive clones were used for ascites production. lmmunoblots indicated that affinity-purified anti-rSP22 immunoglobulin (lg) and ascites lg recognized denatured and native SP22, respectively. Linear epitope mapping of the 189-amino acid SP22 sequence revealed 3 distinct peptide sequences recognized by anti-rSP22 lg, and 1 sequence recognized by ascites lg. Cytoplasm of round spermatids and heads of elongating/elongated spermatids immunostained with both anti-rSP22 and ascites O ur initial work described the diminution of a 22-kilodalton (kd) protein in detergent extracts of cauda epididymal sperm from animals exposed for 4 days to epididymal toxicants such as ethane dimethanesulphonate, chloroethylmethanesulphonate, epichlorohydrin, and the known antiandrogen, hydroxyftutamide (Klinefelter et al, 1997). This protein, known as SP22, was the only silver-stained protein out of 120 proteins resolved by twodimensional (2-D) gel electrophoresis that was quantitatively altered in a dose-related and treatment-related fashThe information in this document has been funded wholly (or in part) by the US Environmental Protection Agency. It has been subjected to review by the National Health and Environmental Effects Research Laboratory and approved for publication. Approval does not signify that the contents reflect the views of the Environmental Protection Agency, nor does mention of trade names or commercial products constitute endorsement or recommendation for use.Correspondence to: Gary R. Klinefelter, NHEERL, RTD, MD #72, Research Triangle Park, NC 277 l l (e-mail: klinefelter.gary@epa.gov).Received for publication June l l , 200 1; accepted for publication July 24, 2001. 48antibodies. Isolated rete testis sperm revealed discrete staining over the cytoplasmic droplet, whereas staining was apparent over the equatorial segment of the head by the time sperm reached the caput epididymidis. Clear cells were, interestingly, immunostained along the length of the epididymis. Ascites lg and anti-SP22 lg each recognized the equatorial segment of sperm heads from rat, hamster, bull , rabbit, and human. Ascites lg and affinity-purified anti-rSP22 lg each significantly inhibited the fertility of cauda epididymal sperm from the rat in vivo, as well as the fertilization rates of cauda epididymal sperm in vitro. Moreover, affinity-purified anti-rSP2...

The fibrous sheath is a major cytoskeletal structure in the principal piece of the mammalian sperm flagellum. We have cloned a cDNA and used it to characterize the expression of mRNA for a mouse sperm fibrous sheath protein. Peptides from a tryptic digest of fibrous sheath proteins were separated by HPLC and a 31 amino acid sequence was obtained from one of the peptides. Through the use of degenerate oligonucleotide polymerase chain reaction (PCR) primers predicted from this sequence, an 80-bp product was amplified from mouse testis first-strand cDNA. This was utilized as a probe to isolate a 2.9-kb cDNA clone from a mouse round spermatid cDNA library. Sequence analysis of the cDNA clone showed that it encodes a protein with an open reading frame of 849 amino acids and includes the original peptide sequence. The predicted protein has a molecular weight of 93,795 and contains 32 cysteine residues and 32 potential phosphorylation sites. It has no significant homology with other known cytoskeletal proteins. Northern blot analysis detected an mRNA of approximately 3 kb that was abundant in round spermatids of the mouse and in testes from six other mammalian species, but not in twelve somatic tissues from the mouse. In situ hybridization analysis indicated that the mRNA is first detected in step 1-6 spermatids, is most abundant in step 8-12 spermatids, and decreases in amount in step 13-15 spermatids, suggesting that expression of the mRNA occurs in the postmeiotic phase of spermatogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)