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PubMed2003

Lipoprotein lipase (LpL) on the surface of cardiomyocytes increases lipid uptake and produces a cardiomyopathy.

Lipoprotein lipase is the principal enzyme that hydrolyzes circulating triglycerides and liberates free fatty acids that can be used as energy by cardiac muscle. Although lipoprotein lipase is expressed by and is found on the surface of cardiomyocytes, its transfer to the luminal surface of endothelial cells is thought to be required for lipoprotein lipase actions. To study whether nontransferable lipoprotein lipase has physiological actions, we placed an alpha-myosin heavy-chain promoter upstream of a human lipoprotein lipase minigene construct with a glycosylphosphatidylinositol anchoring sequence on the carboxyl terminal region. Hearts of transgenic mice expressed the altered lipoprotein lipase, and the protein localized to the surface of cardiomyocytes. Hearts, but not postheparin plasma, of these mice contained human lipoprotein lipase activity. More lipid accumulated in hearts expressing the transgene; the myocytes were enlarged and exhibited abnormal architecture. Hearts of transgenic mice were dilated, and left ventricular systolic function was impaired. Thus, lipoprotein lipase expressed on the surface of cardiomyocytes can increase lipid uptake and produce cardiomyopathy.

Animals↗
PubMed2003

Gene duplication, the evolution of novel gene functions, and detecting functional divergence of duplicates in silico.

Duplication of genes increases the amount of genetic material on which evolution can work and has been considered of major importance for the development of biological novelties or to explain important transitions that have occurred during biological evolution. Recently, much research has been devoted to the study of the evolutionary and functional divergence of duplicated genes. Since the majority of genes are part of gene families, there is considerable interest in predicting differences in function between duplicates and assessing the functional redundancy of genes within gene families. In this review, we discuss the strengths and limitations of both older and novel approaches to investigate the evolution of duplicated genes in silico.

Algorithms↗
PubMed1992

Conjugation of soluble CD4 without loss of biological activity via a novel carbohydrate-directed cross-linking reagent.

Chemical conjugates of recombinant soluble CD4 (sCD4) with toxins, or with antibodies that activate cytotoxic T cells, can be used to direct selective killing of human immunodeficiency virus (HIV)-infected cells. This approach takes advantage of the ability of sCD4 to bind with high affinity to gp120, the envelope protein of HIV-1, which is expressed on actively infected cells. However, conjugation of sCD4 via reagents that target amino groups may reduce its affinity for gp120, since at least one such group is important for gp120 binding. Here, we describe a novel cross-linking reagent which enables the conjugation of sCD4 via its carbohydrate moieties rather than its free amino groups. This heterobifunctional reagent, 4-(4-N-maleimidophenyl)butyric acid hydrazide (MPBH), combines a nucleophilic hydrazide with an electrophilic maleimide, thereby allowing coupling of carbohydrate-derived aldehydes to free thiols. We describe conditions by which MPBH is coupled selectively to the sialic acid residues of sCD4, and exemplify the use of MPBH by conjugating sCD4 to hemoglobin and to beta-galactosidase. We show that, whereas conjugation of sCD4 via amino groups markedly reduces its gp120 binding affinity, conjugation via the carbohydrate chains using MPBH does not affect binding. Moreover, we demonstrate the ability of a sCD4-MPBH-fluorescein conjugate to label HIV-infected human CEM cells selectively. These results indicate that, by targeting its carbohydrate moieties, sCD4 can be cross-linked to other molecules without compromising its function. The approach described here can be useful for glycoproteins in which amino groups, but not carbohydrates, are important for function. More generally, this approach can be considered for use in cross-linking glycoconjugates to compounds which either contain thiols, or to which thiols can be added.

CD4 Antigens↗
PubMed1997

Aging and executive function skills: an examination of a community-dwelling older adult population.

The purpose of the present study was to employ the Tower of Hanoi task to the study of possible changes in executive function skills in older adults. The study used a quasi-experimental design, with age group (i.e., young adult, young elderly, or older elderly), being the independent variable in examining performance differences between younger and older adults. Data were analyzed cross-sectionally by age group. Nineteen elderly men and women comprised two groups; nine Young Elderly with an average age of 65 years and ten Older Elderly with an average age of 75 years. Two men and ten women served as a Young Adult comparison group having an average age of 19 years. Performance on the Tower of Hanoi was measured by efficiency scores (number of trials to consecutive solutions), frequency of error types, self-correction scores (completing the goal configuration in twenty or fewer moves after committing an error precluding a "correct" solution), and error perseveration (committing the same error on two consecutive trials of a problem). Analysis of variance and chi-squared tests suggested similar executive capacities among the 9 young adult and the 8 young elderly participants as compared to their 7 older elderly peers on the 3-disk task. However, on the 4-disk task where problem complexity increased by the addition of another disk and longer move sequences, young adult participants showed superior performance on the average than either young elderly or older elderly participants. Although the present study is limited by the small sample size and the use of cross-sectional analyses to examine age differences, these findings are consistent with the hypothesis of age differences in executive function.

Adult↗
PubMedDate not supplied

Editors' requests of peer reviewers: a study and a proposal.

BACKGROUND: Despite the pivotal role of peer review in the scientific process, there has never been a formal study of the way in which reviewers' opinions are elicited. This article describes such a study and makes recommendations for a more standardized approach to the peer review process. We hope, through this publication and related efforts, to encourage such a process in Preventive Medicine and in other journals. METHOD: The study population included the top 100 journals (as rated by the 1989 Institute for Scientific Information citation frequency index). Only journals with primarily U.S.-based editorial offices are included (n = 73). Participants provided their reviewer forms, cover letters for reviewers, and instructions for reviewers that were used routinely. All data were collected in February 1992. RESULTS: The response rate was 97.3%. Journals varied substantially in many of their reviewer requests. While 96% of journals asked reviewers to recommend acceptance or rejection, only 72% asked reviewers to assess manuscripts' novelty, 69% requested assessments of clarity, and only 51% asked for assessments of the reasonableness of manuscripts' conclusions. Similarly, only 46% of journals reminded reviewers that manuscripts were confidential documents, 51% provided a separate cover letter, and 25% provided extensive (>1 full page) reviewer instructions. CONCLUSIONS: While review uniformity is not requisite, differences between review protocols may not be a function of specific journals' needs, but of some journals' excluding important review components from explicit mention. Based in part on the Council of Biology Editors' recommendations, standard components of reviews and of instructions for reviewers are suggested. If editors' expectations were more explicit, reviewers' comments could better serve editorial needs.

Humans↗
PubMed2006

Openness to attitude change as a function of temporal perspective.

Three studies investigated the impact of temporal perspective on people's dominant social goals and explored the implications of these goals for openness to attitude change. Participants who perceived time as limited expressed social preferences in accordance with emotion-regulation goals (Study 1), were more prone to modify their attitude to bring it into line with the attitude of an anticipated social partner (Study 2), and were more likely to go along with peer consensus opinion on a campus issue (Study 3) than were participants who perceived time as expansive. These studies demonstrate that perception of time plays a vital role in motivating social goals within the persuasion context.

Adult↗
PubMed2006

Osteoarthritis and nutrition. From nutraceuticals to functional foods: a systematic review of the scientific evidence.

The scientific and medical community remains skeptical regarding the efficacy of nutrition for osteoarthritis despite their broad acceptation by patients. In this context, this paper systematically reviews human clinical trials evaluating the effects of nutritional compounds on osteoarthritis. We searched the Medline, Embase, and Biosis databases from their inception to September 2005 using the terms random, double-blind method, trial, study, placebo, and osteoarthritis. We selected all peer-reviewed articles reporting the results of randomised human clinical trials (RCTs) in osteoarthritis that investigated the effects of oral interventions based on natural molecules. Studies on glucosamine and chondroitin sulfate were excluded. The quality of the RCTs was assessed with an osteoarthritic-specific standardised set of 12 criteria and a validated instrument. A best-evidence synthesis was used to categorise the scientific evidence behind each nutritional compound as good, moderate, or limited. A summary of the most relevant in vitro and animal studies is used to shed light on the potential mechanisms of action. Inclusion criteria were met by 53 RCTs out of the 2,026 identified studies. Good evidence was found for avocado soybean unsaponifiables. Moderate evidence was found for methylsulfonylmethane and SKI306X, a cocktail of plant extracts. Limited evidence was found for the Chinese plant extract duhuo jisheng Wan, cetyl myristoleate, lipids from green-lipped mussels, and plant extracts from Harpagophytum procumbens. Overall, scientific evidence exists for some specific nutritional interventions to provide symptom relief to osteoarthritic patients. It remains to be investigated whether nutritional compounds can have structure-modifying effects.

Dietary Supplements↗
PubMed1987

Psychological evaluation and preparation of the patient and family.

The suspected and confirmed diagnosis of cancer places stress on the patient and the family. In addition to the feelings of helplessness, guilt, frustration, alienation, and vulnerability that a diagnosis of cancer provokes, the diagnosis of gynecologic cancer can exacerbate these feelings due to its relationship to the perceived physiologic core of femininity, sexuality, and motherhood. Evaluation of the patient's existing coping skills, perceived seriousness of the illness, anticipated loss of control over physical functioning, and available family support is an essential part of the treatment plan. Preparing the patient and family for diagnosis and treatment is enhanced by supportive intervention techniques such as provision of accurate information, exploration of the patient's fears and fantasies, restoration of degrees of control in the patient's life, and exposure to peer support groups.

Adaptation, Psychological↗
PubMed2000

Neurodevelopmental and psychosocial aspects of Turner syndrome.

Turner syndrome (TS) is the complex phenotype of human females with complete or partial absence of the second sex chromosome, or monosomy X. A characteristic neurocognitive and psychosocial profile has also been described in TS females. Typically, specific deficits in visual-spatial/perceptual abilities, nonverbal memory function, motor function, executive function, and attentional abilities occur in TS children and adults of varying races and socioeconomic status. TS-associated psychosocial difficulties occur in the areas of maturity and social skills. We hypothesize that a subset of the neurocognitive deficits (visual-spatial/perceptual abilities) are genetically determined and result from abnormal expression of one or more X chromosome genes. In addition, a different subset of these neurocognitive deficits (memory, reaction time, and speeded motor function) result from estrogen deficiency and are at least somewhat reversible with estrogen treatment. The TS-associated psychosocial problems are most likely linked to these core neurocognitive deficits and do not reflect a separate and independent component of the syndrome. Turner syndrome research has progressed significantly over the last decade. The field has moved from descriptive reports based on single individuals or small clinical samples to the use of experimental designs with larger, more diverse and representative samples. This degree of variability among individuals with Turner syndrome in all domains (karyotype or genetic constitution, physical attributes, neurocognitive and social functioning) suggests the need to identify risk and protective factors contributing to the heterogeneity in the phenotype. Active education about TS and participation in patient advocacy groups such as the Turner Syndrome Society of the United States (http://www. turner-syndrome-us.org/) has provided new information for TS adults and families as well as a supportive peer group. MRDD Research Reviews 2000;6:135-141.

Adaptation, Psychological↗
PubMed1982

Parental interpersonal perceptual style, child adjustment, and parent-child interactions.

This research examined relationships between parental interpersonal perceptual style (IPS)--the extent to which they are biased in their perceptions of children's behaviors--and (a) the adjustment of their own children and (b) parent-child interactions. In two studies, groups of parents first viewed a videotape of a male or female "target" child interacting with an adult in a playroom and then completed a behavior checklist about the target child that measured their IPS. In Study 1, parents' (especially fathers') IPS was found to be related to interaction between them and their 5-to-7-year-old child; for example, the less negatively biased the father was, the more likely the child was to openly display antagonistic behavior toward his or her parents. In Study 2, fathers' (but not mothers') IPS was found to be related to the teacher- and peer-assessed level of psychosocial adjustment of their own third-grade child; fathers of "problem" children tended to be more negatively biased in their perceptions than were fathers of either "adequate" or "highly adjusted" children. Findings are discussed in terms of their implications for understanding the role that person perception processes play in family functioning and child development.

Attitude↗
PubMed1989

The timing of major life events: effects of departing from the social clock.

It is widely believed that social norms govern the timing of major life events, such that events experienced off time are considerably more stressful than events experienced on time. Experiencing life events either earlier or later than one's peers presumably reduces opportunities for social support and may also invite social disapproval. Relatively few empirical studies have investigated these ideas, however, and those that have suffer from several limitations. The present study made use of a general population survey to investigate the effects of normative versus nonnormative timing of major life events on psychological functioning, interpersonal resources, and interpersonal tensions. Desirable and undesirable events were examined separately, as were the effects of departures from perceived versus statistical age norms. The results of the study offered only limited support for social clock theory. Implications for further research and for the relevance of the theory in a less age-differentiated society are discussed.

Adaptation, Psychological↗
PubMed2006

The impact of delayed development on the quality of life of adults with end-stage renal disease since childhood.

Little is known about the impact of the course of life of children with end-stage renal disease (ESRD) on their quality of life in adulthood. We therefore assessed the course of life of adult patients with onset of ESRD at an age of <15 years between 1972 and 1992 and compared it with that of the general population. Furthermore, we explored how course of life is associated with quality of life (QoL) in young adulthood. A total of 75 young adult patients who had had ESRD since childhood, aged between 20 years and 30 years, completed the RAND-36 Health Survey and a questionnaire, which retrospectively assesses the achievement of development milestones. Patients achieved fewer milestones than peers with respect to autonomy, social, and psycho-sexual development, and displayed less risk behaviour. Patients who achieved fewer social milestones while growing up experienced more emotional problems and less vitality, and they had a lesser overall mental quality of life. Paediatric nephrologists should pay more attention to the development of social and independent functioning of children with ESRD in order to prepare them for active participation in society in adult life.

Adult↗
PubMed1998

Depression following traumatic brain injury.

OBJECTIVE: Review the existing literature on the incidence, neurobiological and psychosocial correlates, and methods of assessment and treatment of depression following traumatic brain injury (TBI). DATA SOURCES: Computerized database searches of the English-language literature from Index Medicus, Psychological Abstracts, Excerpta Medica, and Cumulative Index of Nursing and Allied Health Literature. STUDY SELECTION: Given the relatively small number of publications specifically related to TBI and depression, all studies appearing in the peer-reviewed literature were included in the review. In addition, studies examining depression and other neurologic diseases (eg, stroke) were also reviewed as to the potential applicability of the theoretical model or methodology used. CONCLUSIONS: Depression occurs with sufficient frequency to be considered a significant consequence after TBI. Depression can impede the achievement of optimal functional outcome, whether in the acute or chronic stages of recovery. It appears that a combination of neuroanatomic, neurochemical, and psychosocial factors is responsible for the onset and maintenance of depression. Its treatment is typically psychopharmacologic, with best results obtained from nontricyclic antidepressants. These results have not been confirmed in double-blind clinical trials, however. Future research should use comprehensive, integrative models of depression that include demographic, biologic, and psychosocial factors; enhanced functional neuroimaging techniques; controlled studies of psychopharmacologic and other interventions; and prospective designs with long-term follow-up.

Antidepressive Agents↗
PubMed1989

A developmental analysis of rule-following.

The development of rule-governed behavior begins when a class of verbal forms called instructions, in conjunction with other variables, systematically occasion functional consequences for compliance (or noncompliance). These instructional forms then function as specific stimulus controls for compliance, with the other variables potentially taking on conjoint or conditional stimulus control of that compliance. Experience with numerous instructions occasioning functional consequences for compliance can establish generalized compliance to an indefinitely large stimulus class of instructions, a stimulus class that readily and naturally includes those forms that describe relationships between events and response to them that we also call rules. The important conjoint variables may well be the instruction giver (rule stater), any of their other systematic characteristics that have occasioned functional consequences for compliance in the past, and the topography of the response requested. Generalization of compliance across people, settings, and topography can occur; this generalization can extend to self-instruction, and can fail to extend to certain topographies ("Thou shalt not kill"), certain rule staters (nonpeers who say "Don't use drugs" when peers say it is fun), and certain settings ("Don't play with John in class"). Finally, children's experiences with describing behavior can lead to new self-instructions that fit the already established discriminative-stimulus class of rules and instructions for compliance, so that the novel self-instruction produces compliance. Compliance-oriented research has demonstrated how instruction givers can establish instructions as a discriminative-stimulus class for compliance, and how generalized compliance to new instructions and new instruction givers can be accomplished. Correspondence-training research has demonstrated that self-instructions can become discriminative for later performance of the described behaviors. Self-instruction research suggests that these forms of instructions also can control subsequent behavior, and that instructions and rules may be produced covertly as well as overtly. What has yet to be demonstrated is an ability to produce a novel self-instruction that controls subsequent behavior. The argument has been that the development of a behavior class, compliance to instructions, could provide a reasonable explanation for the acquisition of rule-governed behavior. Experiences within the natural environment, as well as research on compliance, correspondence, and self-instruction, suggest that a behavior class, compliance to instructions, could provide a reasonable model of the acquisition and ge

Behaviorism↗
PubMed1983

Using water mist to reduce self-injurious and stereotypic behavior.

A mist of water sprayed in the face was used as a punisher for stereotypic and self-injurious behaviors by a boy diagnosed as severely mentally retarded with autistic-like behaviors. The boy had a long history of mouthing and hand-biting behaviors. The latter behavior was evinced by noticeable scar tissue on the backs of his hands. The study took place in a self-contained public school classroom for autistic children and other children with severe communication disorders and functional mental retardation. An ABAB withdrawal design with no treatment probes demonstrated the rapid and dramatic suppressive effects that the response-contingent water mist had on the target behaviors. This procedure was taught to classroom personnel who were able to maintain the suppression with minimal interruption of educational programming for the subject or his peers. No adverse physical effects were observed nor did the child attempt to escape or struggle against the procedure. The results are discussed in relation to ethical considerations and the use of response-contingent aversive stimulation.

Autistic Disorder↗
PubMed1992

The outcome of childhood conduct disorder: implications for defining adult personality disorder and conduct disorder.

The effect of conduct disorder on adult social functioning in the areas of work, sexual/love relationships, social relationships and criminality was studied in a sample of young adults who spent much of their childhoods in group-cottage children's homes and an inner-city comparison group. Most subjects with conduct disorder had pervasive (but not necessarily severe) social difficulties compared to peers without conduct disorder. Less than half of this group met DSM-III adult criteria for antisocial personality disorder and just over half were given a diagnosis of personality disorder on interviewer clinical ratings. A latent class model that used both the retrospective and contemporaneous indicators of conduct disorder confirmed the very high continuity with adult social difficulties. Current diagnoses did not adequately describe this group and conduct disorder appeared to be an almost necessary condition for multiple social disability in adults in these samples.

Adolescent↗
PubMed2004

Emotion-related abilities and depressive symptoms in Latina mothers and their children.

This study examined the abilities of 40 Latina mothers and their 6- to 11-year-old children (20 girls, 20 boys) to recognize and produce emotion expressions and how these abilities differed as a function of maternal depressive symptoms. The results indicated that depressively symptomatic mothers were less accurate at recognizing basic emotions (e.g., happy, sad, etc.) and some mixed emotions (e.g., scared/ok combinations) than nonsymptomatic mothers, but there were no group differences for emotion production. In contrast, children of symptomatic mothers posed fewer recognizable sad expressions than their peers. Error pattern analyses also revealed that children of symptomatic mothers were more likely to mistakenly recognize happiness and to avoid posing sadness (across all basic emotions). Children's ability to pose emotions was related to their mothers' emotion production, and this was not moderated by maternal depressive symptoms. The discussion focuses on the possible interpersonal consequences of these biases and deficits in the emotion-related abilities of symptomatic mothers and their children and on the need to conduct research on the familial and cultural processes that might underlie these findings.

Affect↗
PubMed1992

Listening and language at 4 years of age: effects of early otitis media.

The effect of early otitis media on preschoolers' listening and language abilities was examined in a cohort of prospectively followed children. At 4 years of age, children considered otitis negative and otitis positive during the first year of life were examined using a speech-in-competition task and several standardized measures of language and cognitive function. An adaptive test procedure was used, with sentence materials from the Pediatric Speech Intelligibility Test (PSI) (Jerger & Jerger, 1984). Results indicated that children with positive histories of otitis media during the first year required a more advantageous signal-to-competition ratio to perform at 50% sentence intelligibility than did their otitis-negative peers. There was no interaction between birth status (high-risk or full-term) and adaptive PSI listening task outcome. No differences between the groups were found in either receptive or expressive language abilities or in cognitive abilities. Further, there was no relationship between any language or cognitive measure and the adaptive PSI result.

Child, Preschool↗