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Temperature-sensitive periods of sex determination in Emydid turtles.

In many turtles sex differentiation is controlled by the incubation temperature of the embryo, with low temperatures producing males, high temperatures producing females. This study investigates the developmental period of temperature-sensitivity in two species of emydid turtles, using different combinations of incubation at a male-determining temperature (25 degrees C) and at a female-determining temperature (31 degrees C). The sensitive period extends throughout much of the middle third of development. Sex is more readily influenced by 25 degrees than by 31 degrees, however, so that maleness can be determined much earlier in development than can femaleness. Comparison of these results with a previous study of snapping turtles indicates that the sensitive period occupies somewhat the same developmental interval in these different turtles. However, in snapping turtles, the female-determining temperature used (30 degrees) is more influential than the male-determining temperature (26 degrees), in contrast with these results from emydids.

Animals

Growth, differentiation, and function of the testes in the toad Bufo bufo bufo (L.), with special reference to regulatory capacities: effects of unilateral castration, hypophysectomy, and excision of Bidder's organs.

Function and compensatory growth of the testis have been studied in male toads of varying ages, ranging from postmetamorphosis to adults. All experiments lasted 2 months, starting about September 1. Spermatogenesis was normal in sexually immature, 1-year-old toads. The fastest growing young toads developed secondary sex characteristics, the thumbpads, during the experiment. The data suggest that size is more influential than age in determining the onset of sexual maturation. But body size is not the only factor which influences sexual maturation. The growth response of the remaining testis to unilateral castration decreased with increasing age and size of the toads. Two months after operation the remaining testis had reached the size of two testes in the young toads, whereas the testis showed no significant compensatory growth in the adult-sized toads, whether sexually immature or mature. Hypophysectomy reduced body growth in young toads and prevented a testicular growth response to unilateral castration. Young toads, but no adults, with excised Bidder's organs had larger testes than the control toads. In hypophysectomized, young toads spermatogenesis was still active 2 months after the operation.

Animals

The passerine bird song system as a model in neuroendocrine research.

In the neural system controlling song in passerine birds, gonadal steroid hormones have potent effects on neural growth and differentiation. During ontogeny, sex differences in the secretion of steroid hormones lead to dramatic sex differences in neuron number and structure. In adulthood, sex steroid hormones also cause a significant reorganization of neural circuits. These studies of hormone action have been influential in the development of the field of neuroendocrinology.

Animals

Early innervation of abdominal swimmeret muscles in developing lobsters.

The swimmerets in the abdomen of the lobster Homarus americanus are paired external appendages whose back and forth propulsive movements are brought about largely by a group of power and return stroke muscles located in the lateral abdominal cavity. We find functional innervation of these muscles by several excitatory axons and a single inhibitor in embryonic and stage 1 larval lobsters before the external appendages are even formed. This early innervation is via a few nerve bundles in which branches of the motor axons are intertwined in a complex manner. As the swimmerets develop to maturity in later larval and juvenile stages, the innervation consisting usually of several excitor and a single inhibitor synaptic terminals becomes localized to individual muscles. Patterned synaptic activity in these muscles was not seen in the embryonic and larval stages but has been shown in early juvenile stages, when it coincides with the onset of rhythmic movement of the swimmerets. Consequently, such early innervation of the swimmeret muscles may be influential in establishing the central circuitry for the generation of patterned activity, a possibility that was discounted in a previous study (Proc. Natl. Acad. Sci. USA, 70:954-958).

Abdomen

Incubation temperature and gonadal sex affect growth and physiology in the leopard gecko (Eublepharis macularius), a lizard with temperature-dependent sex determination.

Temperature-dependent sex determination (TSD), in which the temperature at which an egg incubates determines the sex of the individual, occurs in egg-laying reptiles of three separate orders. Previous studies have shown that the embryonic environment can have effects lasting beyond the period of sex determination. We investigated the relative roles of incubation temperature, exogenous estradiol, and gonadal sex (testis vs. ovary) in the differentiation of adult morphological and physiological traits of the leopard gecko, Eublepharis macularius. The results indicate that incubation temperature, steroid hormones, and gonads interact in the development of morphological and physiological characters with incubation temperature resulting in the greatest differences in adult phenotype. Incubation temperature did not affect reproductive success directly, but may influence offspring survival in natural situations through effects on adult female body size. Postnatal hormones seem to be more influential in the formation of adult phenotypes than prenatal hormones. These results demonstrate that TSD species can be used to investigate the effects of the physical environment on development in individuals without a predetermined genetic sex and thus provide further insight into the roles of gonadal sex and the embryonic environment in sexual differentiation.

Animals

Effect of cement pressure and bone strength on polymethylmethacrylate fixation.

The effect of the quality of the bone and of the cement pressurization magnitude and duration on the fixation achieved with polymethylmethacrylate (PMMA) bone cement is studied in vitro. Seventy-one cement-bone interface specimens, prepared under various conditions of pressurization of low-viscosity bone cement, are tested in tension. The load at failure and the maximum cement penetration are measured to assess the fixation achieved, and the quality of the bone is assessed by determining the compressive strength of each of the bone specimens. Statistical analysis of the data indicates that the pressure magnitude is the most influential of the factors considered in the cement penetration behavior and in the development of failure load capacity. The duration of the pressure does not appear to be a significant factor. The cement penetration is a decreasing function of the bone strength, reflecting a decrease in the porosity and an increase in the area fraction. Although not directly measured in these tests, these latter bone properties are indirectly measured by the bone compressive strength. The effect of increasing bone strength on the failure load is nonlinear. The development of adequate failure load capacity is the result of a balance between the cement penetration allowed by the porosity of the bone and the inherent strength of the cancellous bone itself. Weak bone, although adequately penetrated by cement, cannot provide strong fixation. Stronger, denser bone limits cement penetration, but pressurization enhances development of failure load capacity through more complete infusion and interlocking of the cement in the available pore space. The strength of the fixation achievable for any bone is limited by the intrinsic strength of the bone.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomechanical Phenomena

Laser workshops in neurological surgery.

With the recent increased popularity of laser use in neurosurgery, there arises the question of the value and necessity of a "hands-on" laser workshop in preparing the surgeon for clinical use of the instrument. To find an answer, a questionnaire was recently circulated to those who had participated in such a workshop. Participants were asked whether they were actually using the laser clinically since attending the workshop and, if so, the type of laser they were using. Whether the course was influential in their decision to use a laser and whether they felt they could have used the instrument without such a course was also asked. In addition, the surgeons were asked how long it took them to become comfortable using the laser. The types of procedures, the percentage of operative cases and the mode (freehand or microlinked) in which the laser was used was also investigated. Finally, absolute indications for laser use in neurosurgery and methods to improve laser education were sought. The answers were varied and interesting, but it is our conclusion that a "hands-on" workshop is both a valuable and necessary means of preparing a neurosurgeon for clinical use of a laser, and participation in such a course should be encouraged.

Clinical Competence

Perceived choice, social interaction, and dimensions of moral of residents in a home for the aged.

In a study of 50 residents in a home for the aged, the relationships of health at relocation, choice in relocation, income, perceived choice within an institutional environment, and social interaction to four indices of morale were examined in hierarchical multiple regression designs. The theoretical concept of decisional control (i.e., perceived choice) guided the investigation. Significant multivariate effects were found for all dimensions of morale: agitation, attitude toward own aging, lonely dissatisfaction, and a combined morale index. Choice within the institution and social interaction were the major contributors to these significant multivariate relationships, but income was also influential in analysis of the attitudinal and combined morale indices for a subsample. Retrospective measures of health at relocation and choice in relocation were unstable in their contributions to overall multivariate relationships. Relationships of age, recency of loss of a significant other, and length of residency to morale were explored and found not to be significant. Results are discussed against the background of theoretical expectations, and avenues for future research are identified.

Aged

Factors influencing career success in nursing.

The purpose of this descriptive study was to examine educational preparation, personal characteristics, and significant others in the career success of women in nursing. The sample was a random selection of 194 doctorally prepared female nurses who reported some degree of career success. The factor, personal characteristics, was ranked as the most important in facilitating career success, educational preparations was ranked second, and significant others was ranked third. Among significant others ranked as influential were teachers, peer/colleagues, and supervisors.

Achievement

Influences of the social network on choice and duration of breast-feeding in mothers of preterm infants.

A prospective analytic study was conducted to examine the influences of the social network on the choice and duration of breast-feeding among 125 mothers of preterm infants. The Influence of Specific Referents (ISR) Scale was used to measure mothers' perceptions of the wishes of seven social referents regarding feeding choice and to assess mothers' motivation to comply with their referents' wishes. Referents included family members, friends, and health care professionals. Mothers choosing to breast-feed reported greater influence from referents than those choosing to formula-feed. Among the 88 mothers who initiated breast-feeding or expression, the number of supports reported by mothers was the most influential factor on duration of lactation. Women with no source of support were six times more likely to cease lactation than women with six sources of support.

Breast Feeding

Intensive care decisions about level of aggressiveness of care.

Questionnaires were used to assess (a) the factors intensive care unit resident physicians (N = 33) and nurses (N = 57) perceived as influential in making decisions about level of aggressiveness of patient care (LAC), (b) who residents and nurses believed should be involved versus who was involved in decision making, and (c) the amount of collaboration they perceived in their practices. Questionnaires then were used to assess decision making about 314 patients. All providers agreed that patient request influenced their LAC decisions, with possibility of benefit and diagnosis ranked second and third. Although both nurses and residents believed capable patients should be making LAC decisions, providers identified attending physicians as the most common participants in decision making for specific patients. Residents were more satisfied with the decision making process than nurses, t = 2.05 (88), p = .04. There was no relationship between perceptions of nurse-resident collaboration and providers' inclusion of others in the LAC decision process.

Adult

Assessing the adequacy of the logistic regression model for matched case-control studies.

We apply results for the detection of outliers in logistic regression to the analysis of matched pairs data and illustrate the techniques with data from a matched pairs study of the relationship between iron-binding proteins and mortality in the Solomon Islands. Although the study includes 90 matched pairs, the conclusions change substantially with deletion of one or two pairs. Thus, even with reasonably large data sets, single observations may have a great impact on the results of an analysis. The identification of influential observations should constitute part of the analysis of matched case-control data.

Clinical Trials as Topic

Validation techniques for logistic regression models.

This paper presents a comprehensive approach to the validation of logistic prediction models. It reviews measures of overall goodness-of-fit, and indices of calibration and refinement. Using a model-based approach developed by Cox, we adapt logistic regression diagnostic techniques for use in model validation. This allows identification of problematic predictor variables in the prediction model as well as influential observations in the validation data that adversely affect the fit of the model. In appropriate situations, recommendations are made for correction of models that provide poor fit.

Benzothiadiazines

Effect of acute and daily cocaine treatment on extracellular dopamine in the nucleus accumbens.

The behavioral stimulant effect of peripheral cocaine injection into rats is augmented following daily administration. In vivo dialysis in the nucleus accumbens of conscious rats was used to determine if the increased behavioral response following daily cocaine administration is associated with an increase in extracellular dopamine concentration. Acute injection of cocaine (15 mg/kg, ip) produced an elevation in extracellular dopamine concentration in the nucleus accumbens. Following daily pretreatment with cocaine (15 mg/kg, ip X 4 days), a subsequent acute injection of cocaine (15 mg/kg, ip) significantly elevated the extracellular dopamine levels compared to that produced by a single acute injection. Although the levels of extracellular dopamine metabolites was significantly lowered by both acute cocaine and daily cocaine, no difference between these two groups of animals was measured. The increase in extracellular dopamine following a single acute injection of cocaine was not correlated to the motor stimulant response. However, after daily pretreatment with cocaine the motor stimulant response to acute cocaine was positively correlated with the increased extracellular concentration of dopamine in the nucleus accumbens. These data demonstrate that enhanced dopamine release into the nucleus accumbens may mediate the behavioral sensitization produced by daily injections of cocaine, but that other neural systems are influential in mediating the acute motor stimulant effect of cocaine.

3,4-Dihydroxyphenylacetic Acid

Caffeine effects on cyclic AMP levels in the mouse embryonic limb and palate in vitro.

Caffeine is a teratogen that causes limb and palate malformations in rodents. Since the ability to raise cyclic nucleotide levels is a known biological action of caffeine, cyclic AMP levels were measured in CD-1 mouse embryonic forelimb from whole embryo culture and embryonic limb and palate cells grown in primary culture following treatment with various concentrations of caffeine (0, 1, 3, or 10 mM). In forelimb buds from whole embryo culture, a dose-dependent response was observed. Caffeine at 1 mM concentration stimulated cyclic AMP levels to 151% of control value at 60 min. Even greater stimulation of cyclic AMP occurred at higher caffeine concentrations. A dose-dependent response was seen in both limb and palate cell culture. In limb cell culture, all caffeine concentrations significantly stimulated cyclic AMP after 10 min compared to control. In palate cell culture, there was a twofold increase in cyclic AMP at the 1-mM caffeine concentration. At higher caffeine concentrations, cyclic AMP was significantly increased after 60 min. In addition, stimulation of cyclic AMP in cultured limb and palate cells by isoproterenol, a beta-adrenergic agonist, was used as a positive control. Isoproterenol stimulated a 2.5-fold greater response in the palate cells than in the limb bud cells at isoproterenol levels of 10(-5) or 10(-4) M. The increase of cyclic AMP may be influential in the process of abnormal limb or palate development.

Animals

Transplacental distribution of weak acids in mice: accumulation in compartments of high pH.

The transplacental distribution of three weak acids was measured in mice on gestational day 11. The ratio of drug concentration in maternal, embryonic, and extraembryonic compartments compared to maternal plasma followed a consistent hierarchy such that amniotic fluid greater than or equal to exocoelomic fluid greater than embryo greater than embryo plasma greater than maternal skeletal muscle. This distribution pattern correlates well with pH in these compartments and suggests that pH gradients between compartments are an influential factor in determining weak acid drug disposition during pregnancy.

Acids

Mathematical model of antiviral immune response. III. Influenza A virus infection.

We present an approach to studying theoretically the regularities and the kinetic characteristics of influenza A virus (IAV) infection in man. The estimates of the "numbers" (Zinkernagel et al., 1985) characterizing evolutionary established interferon and immune responses in uncomplicated IAV infection are explored by developing a multiparameter mathematical model which allows direct quantitative references to the biological reality. The system of equations of the mathematical model of antiviral immune response, applied earlier to acute hepatitis B virus infection (Marchuk et al., 1991a, b), is modified and extended to describe the joint reaction of the interferon and immune systems in IAV infection. Macrophages infiltrating the airway's epithelium are considered to be the principal source of interferon that induces antiviral resistance in lung epithelial cells. The model is formulated as a delay-differential system with about 60 parameters characterizing the rates of various processes contributing to the typical course of IAV infection. The key aspect of the adjustment between the model and various data on the immunity to influenza is the derivation of a consistent data set--the generalized picture of uncomplicated IAV infection. It serves as a consistent theoretical definition of the structure of the normal course of the infection and the antiviral immune response suitable for model fitting. The parameter estimates for the processes considered in the model are carefully discussed. The quantitative model is used to study the organization and dynamic properties of the processes contributing to IAV infection. The threshold condition for immune protection of virus-free host to infection with IAV is analyzed. The relative roles of humoral, cellular and interferon reactions for the kinetics of the uncomplicated IAV infection are studied. The contribution of parameters of virus-sensitive tissue, interferon and IAV-specific immune processes to the variations of duration and severity of the infection is quantitatively estimated by sensitivity studies. It is shown that the variations in the parameters of a virus-epithelial cell system are more influential on the severity of the infection rather than that of the antiviral immune response. The need for fine co-ordination of the kinetics of the non-specific interferon response and the adaptive antigen-specific immune reactions to provide recovery from the infection is illustrated.

Humans

Social drinking as a health and psychosocial risk factor. Anstie's limit revisited.

This chapter reviews empirical evidence dealing with the risk of using beverage alcohol in quantities generally considered to be within the range of moderate or social drinking. It begins with a discussion of terms and concepts typically employed to define the limits of moderate and social drinking. The historical debate over moderate drinking is considered next, using Francis Anstie's daily limit of 1.5 oz of absolute ethanol as an example of an influential and enduring approach to this issue. The scientific evidence relevant to the association between moderate drinking and damage is reviewed in sections dealing with the risks of acute ingestion of alcohol and the hazards of chronic drinking. In a final section, a multidimensional model of risk is developed to serve as a basis for early intervention and prevention planning. It is concluded that both social and moderate drinking entail risk of health hazards and psychosocial consequences. These risks are not always a direct function of the amount of ethanol consumed but rather reflect complex interactions among a host of antecedent and mediating variables. When these are taken into account, a better estimate of the relative risk of different consequences of drinking can be made.

Alcohol Drinking